G.L. Zimmerman, DVM, Ph.D.
Zimmerman Research
Livingston, MT

3. General Design:

a. Purpose: This study was designed to confirm the effective dose for the control of natural nematode infections in cattle.

b. Animals: Twenty-four mixed beef breed heifers, weighing between 177 and 334 kg, were randomly assigned to one of three treatment groups (8 per group) based on pretreatment fecal nematode egg counts.

c. Housing: Animals were maintained in outdoor pens with dirt floors by treatment group and exposed to ambient weather conditions.

d. Infection: All cattle had naturally-acquired nematode infections.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 0.5, or 1 mL/10 kg body weight providing 0.25, or 0.5 mg moxidectin/kg body weight, respectively.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Necropsy was on Day 14 or 15 posttreatment.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number B-93-12

1. Type of Study: Dose confirmation study in cattle with naturally-acquired gastrointestinal roundworm infections.

2. Investigator: J. A. DiPietro, D.V.M., M.S. College of Veterinary Medicine University of Illinois Urbana, IL

3. General Design:

a. Purpose: This study was designed to confirm the effective dose for the control of natural nematode infections in cattle.

b. Animals: Thirty mixed beef breed calves, weighing between 138 and 223 kg, were randomly assigned to one of three treatment groups (10 per group) based on pretreatment fecal nematode egg counts and body weight.

c. Housing: Animals were housed indoors in pens with concrete floors by treatment group.

d. Infection: All cattle had naturally-acquired nematode infections.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 0.5, or 1 mL/10 kg body weight providing 0.25, or 0.5 mg moxidectin/kg body weight, respectively.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Necropsy was on Day 14 or 15 posttreatment.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number 0863-B1-CN-03-92

1. Type of Study: Dose confirmation study in cattle with naturally-acquired gastrointestinal roundworm infections.

2. Investigators: S. Ranjan, B.V.Sc., Ph.D.
and R.K. Prichard, B.Sc., Ph.D.
McGill University
MacDonald Campus
Ste-Anne de Bellevue
Quebec, Canada

3. General Design:

a. Purpose: This study was designed to confirm the effective dose required for the control of nematode infections in cattle.

b. Animals: Twenty-four mixed beef breed male calves, weighing between 129 and 160 kg, were randomly assigned to one of three treatment groups (8 per group) based on pretreatment fecal nematode egg counts.

c. Housing: Animals were maintained on pasture until treatment and then commingled in a barn following treatment.

d. Infection: All cattle had naturally-acquired nematode infections.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 0.5, or 1 mL/10 kg body weight providing 0.25, or 0.5 mg moxidectin/kg body weight, respectively.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Necropsy was on Day 14 or 15 posttreatment.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number B-93-10

1. Type of Study: Dose confirmation study in cattle with naturally-acquired and experimentally-induced gastrointestinal roundworm infections.

2. Investigator: L.R. Cruthers, Ph.D.
Professional Laboratory and Research Services, Inc.
Corapeake, NC

3. General Design:

a. Purpose: This study was designed to confirm the effective dose for the control of nematode infections in cattle.

b. Animals: Thirty mixed beef breed calves, weighing between 168 and 255 kg, were randomly assigned to one of three treatment groups (10 per group) based on pretreatment fecal nematode egg counts.

c. Housing: Animals were maintained in outdoor pens by treatment group and exposed to ambient weather conditions.

d. Infection: Thirty six days prior to treatment, cattle were infected with approximately 10,000 third-stage larvae from the following nematode genera: Nematodirus (2,000 larvae), Cooperia (3,000 larvae), Ostertagia (3,600 larvae) Trichostrongylus (1,200 larvae) and Haemonchus (200 larvae). These induced infections were superimposed over any naturally-acquired nematode burdens carried by these cattle.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 0.5, or 1 mL/10 kg body weight providing 0.25, or 0.5 mg moxidectin/kg body weight, respectively.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Necropsy was on Day 14 or 15 posttreatment.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number B-92-14

1. Type of Study: Dose confirmation study in cattle with naturally-acquired gastrointestinal roundworm infections and induced infections of hookworm and lungworm.

2. Investigator: J.C. Williams, Ph.D. Louisiana State University Baton Rouge, LA

3. General Design:

a. Purpose: This study was designed to confirm the effective dose for the control of nematode infections in cattle.

b. Animals: Twenty mixed beef breed heifers, weighing between 122 and 184 kg, were ranked by pretreatment fecal lungworm larval counts, paired and randomly assigned to either the moxidectin pour-on treated group or the control group.

c. Housing: Animals were maintained in outdoor pens with concrete floors by treatment group and exposed to ambient weather conditions.

d. Infection: Cattle were infected with approximately 2,316 hookworm L3 larvae on Day -77. On Day -29, cattle were infected with approximately 1,509 third-stage hookworm larvae and 1,080 third-stage lungworm larvae. These experimentally-induced infections were superimposed over naturally-acquired nematode infections.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Necropsy was on Day 14 or 15 posttreatment.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number B-90-29

1. Type of Study: Dose confirmation study in cattle with experimentally-induced gastrointestinal roundworm infections.

2. Investigator: J. A. Pankavich, Ph.D.
Cyanamid Agricultural Research Center
Princeton, NJ

c. General Design:

a. Purpose: This study was designed to confirm the effective dose required for the control of nematode infections in cattle using 4 different formulations.

b. Animals: Thirty Angus, Hereford and Angus X Hereford cross heifers weighing between 158 and 228 kg, were randomly assigned to the control and moxidectin treated groups (6 per group) based on pretreatment fecal nematode egg counts.

c. Housing: Animals were housed in a barn in pens by group following treatment.

d. Infection: Twenty-eight days prior to treatment, cattle were infected with third-stage larvae from the following nematode genera/species: Cooperia (19,800 larvae), Ostertagia (38,600 larvae) Trichostrongylus axei (34,400 larvae). Trichostrongylus colubriformis was present in the inoculum as a contaminant.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

h. Controls: Untreated control animals were used.

i. Test Duration: Necropsy was on Day 16 posttreatment.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals administered the formulation intended for marketing are given in the following table.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number 0863-B-US-15-96

1. Type of Study: Dose confirmation study in cattle with induced infections of lungworm.

2. Investigator: L. L. Smith, DVM
Larry Smith Research and Development, Inc.
Lodi, WI

3. General Design:

a. Purpose: This study was designed to confirm the effective dose for the control of larval and adult stages of lungworm in cattle.

b. Animals: Thirty mixed breed calves, mostly Holstein and dairy-beef crosses, weighing between 108 and 167 kg, were randomly assigned to one of three treatment groups based on body weight.

c. Housing: Animals were maintained in pens by treatment group in three separate pens. The pens were attached to a modified open front barn for shelter. Cattle were exposed to ambient weather conditions during the study and the total snowfall during the experimental period was 20.4 inches.

d. Infection: Each animal was experimentally infected with approximately 3,000 lungworm third-stage larvae on Day 0.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied to cattle, once on Day 5 or Day 28 postinfection, at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight. One group of cattle was treated on Day 5 postinfection to evaluate efficacy against fourth-stage lungworm and one group was treated on Day 28 postinfection to evaluate efficacy against the adult stage.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight. Control animals were treated on Day 28 postinfection.

i. Test Duration: Necropsy of all animals was on Day 42 postinfection.

j. Pertinent Parameters Measured: Lungworms were collected at necropsy and subsequently counted by stage.

4. Results: Efficacy data are given in the following table.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Persistent Efficacy - Endoparasites

Three pivotal studies were conducted in the United States to evaluate the persistent activity of moxidectin 0.5% pour-on in preventing infection of treated cattle with third-stage larvae of Ostertagia ostertagi and Dictyocaulus viviparus. The studies had similar designs and consisted of cattle in each treatment group receiving a single challenge of third-stage larvae of both nematode species, on a specific posttreatment day. Inoculum were administered on Days 21, 28, 35 or 42 posttreatment. These studies demonstrated that moxidectin 0.5% pour-on has effective persistent activity for 28 days against Ostertagia ostertagi and 42 days against Dictyocaulus viviparus.

Individual Persistent Efficacy Studies

Study Number 0863-B-US-5-95

1. Type of Study: Dose confirmation study in cattle with induced gastrointestinal roundworm and lungworm infections.

2. Investigator: L. R. Cruthers, Ph.D.
Professional Laboratory and Research Services, Inc.
Corapeake, NC

3. General Design:

a. Purpose: This study was designed to determine the period of time following treatment in which gastrointestinal roundworm and lungworm infections are controlled in cattle.

b. Animals: Forty mixed beef breed heifer calves, weighing between 146 and 208 kg, were randomly assigned to one of five treatment groups (8 per group) based on body weight. Cattle had been treated with an approved anthelmintic at the time of purchase and all cattle were negative for the presence of nematode eggs and lungworm larvae in feces at the start of the study.

c. Housing: Animals were maintained in individual outdoor pens and exposed to ambient weather conditions during the posttreatment period.

d. Infection: On Day 0, each calf was infected with an inoculum containing approximately 25,000 Ostertagia and 1,500 Dictyocaulus viviparus third-stage larvae.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight. There were four different groups of cattle treated with moxidectin pour-on. A different group was treated at 42, 35, 28 and 21 days prior to the experimental larval challenge on Day 0

h. Controls: Untreated control animals were used.

i. Test Duration: Necropsy was on Days 22 or 23 postinfection.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table. The lungworm infection only established in one control calf; therefore, it was not possible to the evaluate persistent efficacy of moxidectin against this nematode in this study.

^aDay is day of treatment with moxidectin pour-on relative to larval infection.
^bO. lyrata males were found in 3 control and 4 animals in the Day 42 group.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number 0863-B-US-6-95

1. Type of Study: Dose confirmation study in cattle with induced gastrointestinal roundworm and lungworm infections.

2. Investigators:

3. General Design:

a. Purpose: This study was designed to determine the period of time following treatment in which gastrointestinal roundworm and lungworm infections are controlled in cattle.

b. Animals: Forty Holstein steer calves, weighing between 133 and 198 kg, were randomly assigned to one of five treatment groups (8 per group) based on body weight. Cattle were treated with an approved anthelmintic at the time of purchase. All cattle were negative for nematode eggs and lungworm larvae in feces at the start of the study.

c. Housing: Animals were maintained in individual pens on concrete floors in a barn during the posttreatment period.

d. Infection: On Day 0, each calf was infected with an inoculum containing approximately 25,000 Ostertagia and 1,500 Dictyocaulus viviparus third-stage larvae.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight. There were four different groups of cattle treated with moxidectin pour-on. A different group was treated at 42, 35, 28 and 21 days prior to the experimental larval challenge on Day 0

h. Controls: Untreated control animals were used.

i. Test Duration: Necropsy was on Day 21 or 22 postinfection.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table.

^aDay is day of treatment with moxidectin pour-on relative to larval infection.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number 0863-B-US-8-96

1. Type of Study: Dose confirmation study in cattle with induced gastrointestinal roundworm and lungworm infections.

2. Investigator: S. Ranjan, B.V.Sc., Ph.D.
Fort Dodge Animal Health
Princeton, NJ

3. General Design:

a. Purpose: This study was designed to demonstrate therapeutic efficacy against established larval infections and to determine the period of time following treatment in which gastrointestinal roundworm and lungworm infections are controlled in cattle.

b. Animals: Forty Holstein calves (20 steers and 20 heifers), weighing between 100 and 154 kg were used. For each sex, calves were ranked by body weight and randomly assigned to one of five treatment groups (4 steers and 4 heifers per group). Cattle had been treated with an approved anthelmintic at the time of purchase and all cattle were negative for the presence of nematode eggs and lungworm larvae in feces at the start of the study.

c. Housing: Animals were maintained in pens on a concrete floor by treatment group by sex (4 animals per pen) in an open front barn.

d. Infection: On Day 0, each calf was infected with an inoculum containing approximately 25,000 Ostertagia and 1,500 Dictyocaulus viviparus third-stage larvae.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight. There were five different groups of cattle treated with moxidectin pour-on. A different group was treated at 42, 35, 28 and 21 days prior to the experimental larval challenge on Day 0 and one group was treated five days postinfection to demonstrate therapeutic efficacy against established larval infections.

h. Controls: Untreated control animals were used.

i. Test Duration: Necropsy was on Day 28 to 30 postinfection.

j. Pertinent Parameters Measured: Nematodes collected at necropsy were subsequently counted and identified.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table.

^aDay is day of treatment with moxidectin pour-on relative to larval infection.

5. Adverse Reactions: No adverse reactions to treatment were observed.

B. Ectoparasite Claims

1. Dose Determination Studies - Mange Mites

Two pivotal experiments (B-91-21 and B-92-15) were conducted to determine the effective dose against experimentally-induced Psoroptes ovis infestations on cattle. In B-91-21, cattle were treated with moxidectin 0.5% pour-on at 0.5, 0.75, or 1.0 mg moxidectin/kg body weight. In B-92-15, cattle were treated with moxidectin 0.5% pour-on at 0.25, 0.50 or 0.75 mg moxidectin/kg body weight. In both studies care was taken to avoid application to the mange lesions. A previous study had demonstrated that the efficacy of the product was decreased if scabs in the pour-on site were not avoided during application. In both studies, weekly mite counts were done on all animals for eight weeks posttreatment. The conclusion derived from these trials was that 0.5 mg moxidectin/kg body weight is the optimal dose of moxidectin pour-on for the control of psoroptic mange.

A dose determination study (B-93-9) was conducted with calves experimentally infested with Chorioptes bovis and treated with moxidectin 0.5% pour-on at either 0.25, 0.50 or 0.75 mg moxidectin/kg body weight. This study demonstrated that moxidectin at 0.50 mg/kg body weight is recommended for the control of Chorioptes bovis infestations in cattle.

Individual Dose Determination Studies

Study Number B-91-21

1. Type of Study: Dose determination study in cattle with induced infestations of Psoroptes ovis.

2. Investigator: B. C. Clymer, Ph.D.
CAVL, Inc. and CRC
Amarillo, TX

3. General Design:

a. Purpose: This study was designed to evaluate the dose required for effective control of Psoroptes ovis infestations in cattle.

b. Animals: Thirty-two mixed English breed heifers, weighing between 150 and 246 kg, were randomly assigned to treatment groups (eight/group) based on pretreatment mite counts.

c. Housing: All animals were housed in individual stanchions from Day -26 to Day 0 in order to establish the infestations. Following treatment cattle were maintained in outdoor pens by treatment group (eight animals/pen) and exposed to ambient weather conditions.

d. Infestation: Cattle were experimentally infested with mites.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 1, 1.5 or 2 mL/10 kg body weight providing 0.5, 0.75 or 1.0 mg moxidectin/kg body weight, respectively.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 2 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Skin scrapings for mite counts were done through Day 56 posttreatment.

j. Pertinent Parameters Measured: Number of live mites found in skin scrapings were counted pretreatment (Day -1) and at eight weekly intervals posttreatment.

4. Results: All 0.5 and 0.75 mg moxidectin/kg animals were negative for mites by Day 42 and 28, respectively. One animal at 1.0 mg moxidectin/kg remained positive throughout the study.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number B-92-15

1. Type of Study: Dose determination study in cattle with induced infestations of Psoroptes ovis.

2. Investigator: H. G. Kinzer, Ph.D.
New Mexico State University
Las Cruces, NM

3. General Design:

a. Purpose: This study was designed to evaluate the dose required for effective control of Psoroptes ovis infestations in cattle.

b. Animals: Twenty-four Hereford cross calves, weighing between 223 and 298 kg, were randomly assigned to treatment groups (six/group) based on pretreatment mite counts.

c. Housing: All animals were housed indoors in individual stanchions within pens.

d. Infestation: Cattle were experimentally infested with mites.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 0.5, 1.0 or 1.5 mL/10 kg body weight providing 0.25, 0.5 or 0.75 mg moxidectin/kg body weight, respectively.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1.5 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Skin scrapings for mite counts were done through Day 56 posttreatment

j. Pertinent Parameters Measured: Number of live mites and mite eggs were counted pretreatment (Day -1) and at eight weekly posttreatment intervals posttreatment.

4. Results: Efficacy data are summarized in the following table.

5. Adverse Reactions: No adverse reactions to treatment were observed. One control animal was removed from the study after week 5 due to life-threatening scabies burden.

Study Number B-93-9

1. Type of Study: Dose determination study in cattle with induced infestations of Chorioptes bovis.

2. Investigator: L.L. Smith, D.V.M.
Larry Smith Research and Development Inc.
Lodi, WI

3. General Design:

a. Purpose: This study was designed to evaluate the dose required for effective control of Chorioptes bovis infestations in cattle.

b. Animals: Twenty-eight female beef-cross calves, weighing between 167 and 311 kg, were randomly assigned to treatment groups (seven/group) based on pretreatment mite counts.

c. Housing: All animals were housed indoors in individual stanchions.

d. Infestation: Cattle were experimentally infested with mites.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 0.5, 1.0 or 1.5 mL/10 kg body weight providing 0.25, 0.5 or 0.75 mg moxidectin/kg body weight, respectively.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1.5 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Skin scrapings for mite and mite egg counts were done through Day 56 posttreatment.

j. Pertinent Parameters Measured: Number of live mites and mite eggs were counted pretreatment (Day -1) and at eight weekly posttreatment intervals.

4. Results: At termination of the study, all control cattle were positive for mites while a total of three mites were found on two animals in the group treated with moxidectin pour-on at 0.5 mg/kg body weight.

5. Adverse Reactions: No adverse reactions to treatment were observed.

Lice Dose Determination Study

A dose determination study was conducted in Wyoming (Experiment B-90-36), in which naturally infested cattle were treated with moxidectin at 0.25, 0.50, and 0.75 mg/kg body weight. Cattle were infested with the sucking lice, Solenopotes capillatus and Linognathus vituli, and the biting louse, Bovicola (Damalinia) bovis. Lice counts were done at weekly intervals for eight weeks posttreatment. All three doses of moxidectin 0.5% pour-on were effective in reducing the numbers of adult and nymphal stages of lice. At trial termination (Day 56 posttreatment), all cattle treated with moxidectin pour-on were free of adult and nymphal stages of all three species of lice with the exception of cattle treated with 0.25 mg moxidectin/kg body weight. The majority of the animals (five of eight) in the 0.25 mg moxidectin/kg group were positive for adult S. capillatus while three of eight animals were positive for nymphs. Based on the proportion of lice-free animals at the trial termination, the minimum fully effective dose against adult S. capillatus was 0.5 mg moxidectin/kg body weight.

Study Number B-90-36

1. Type of Study: Dose determination study in cattle with naturally-acquired lice infestations.

2. Investigator: J.E. Lloyd, Ph.D.
University of Wyoming
Laramie, WY

3. General Design:

a. Purpose: This study was designed to evaluate the dose required for effective control of lice infestations in cattle.

b. Animals: Thirty-two Hereford and Hereford X Angus cross beef cattle, weighing between 157 and 331 kg, were randomly assigned to treatment groups (eight/group) based on pretreatment counts of total adult and nymphal Solenopotes capillatus.

c. Housing: Following treatment cattle were maintained in outdoor pens by treatment group (eight animals/pen) and exposed to ambient weather conditions.

d. Infestation: All cattle had naturally-acquired lice infestations.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 0.5, 1.0 or 1.5 mL/10 kg body weight providing 0.25, 0.5 or 0.75 mg moxidectin/kg body weight, respectively.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1.5 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Lice counts were conducted for 56 days

j. Pertinent Parameters Measured: Lice were counted weekly at eight predilection sites on each animal for eight weeks posttreatment.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following tables.

Lice Counts and % Reduction of adult and nymphal Bovicola bovis by moxidectin pour-on

Lice Counts and % Reduction of adult and nymphal Solenopotes capillatus by moxidectin pour-on

Lice Counts and % Reduction of adult and nymphal Linognathus vituli by moxidectin pour-on

5. Adverse Reactions: No adverse reactions to treatment were observed. One animal in the 0.5 mg/kg treatment group died due to Clostridium novyi infection which was not related to moxidectin treatment.

2. Dose Confirmation Studies - Mange Mites

Study Number 0863-B-US-14-96

1. Type of Study: Dose confirmation study in cattle with naturally-acquired infestations of Chorioptes bovis.

2. Investigator: L.L. Smith, D.V.M.
Larry Smith Research and Development, Inc.
Lodi, WI

3. General Design:

a. Purpose: This study was designed to confirm the effective dose required for control of Chorioptes bovis infestations in cattle.

b. Animals: Twenty mature mixed breed dairy cows, weighing between 381 and 675 kg, were randomly assigned to treatment groups (ten/group) based on pretreatment mite counts.

c. Housing: All cows were housed indoors in individual stanchions.

d. Infestation: Cattle were purchased from local farms from which they had naturally-acquired the mite infestations.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to cows at 1 mL/10 kg body weight providing 0.5 moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to cows at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Skin scrapings for mite and egg counts were done through Day 56 posttreatment.

j. Pertinent Parameters Measured: Number of live mites and mite eggs were counted pretreatment (Day -1) and at eight weekly posttreatment intervals posttreatment.

4. Results: The Day 0 count was 468.0 for the control group and 478.8 for the treated group. All control cattle were positive for mites and mite eggs throughout the study. Two moxidectin treated animals were positive for mites and one was positive for mite eggs at study termination (Day 56 posttreatment).

5. Adverse Reactions: No adverse reactions to treatment were observed. One control animal was removed from the study after the week 6 counts as the result of a uterine torsion. This condition was not study related.

Dose Confirmation Studies - Lice and Cattle Grubs

Two study types were used to confirm the efficacy of the 0.5 mg moxidectin/kg dose against both sucking and biting lice. One study type (B-93-4) was designed only to evaluate efficacy against lice (Linognathus vituli, Solenopotes capillatus, Haematopinus eurysternus, and Bovicola bovis). The second study type (B-91-24) used cattle which were infested with both lice (Haematopinus eurysternus and Bovicola bovis) and cattle grubs allowing efficacy evaluation against both parasite types concurrently. These studies evaluated efficacy against lice using naturally infested cattle treated with 0.5 mg moxidectin/kg versus cattle treated with pour-on vehicle. The dose determination study (B-90-36) serves as the second dose confirmation study for Linognathus vituli and Solenopotes capillatus. It was conclusively demonstrated that moxidectin 0.5% pour-on at the proposed recommended dose of 0.5 mg moxidectin/kg body weight provided excellent control of both adult and nymphal stages of the sucking lice, Linognathus vituli, Solenopotes capillatus, and Haematopinus eurysternus, and the biting louse, Bovicola (Damalinia) bovis.

Efficacy against migrating larval stages of the northern cattle grub, Hypoderma bovis, was evaluated in two pivotal studies (B-91-24 and B-91-20). These studies contained a combined total of 60 control animals of which 49 were infested with H. bovis larvae and a combined total of 59 treated animals of which only one animal was positive (a total of three 3rd instars emerged).

Two pivotal studies (B-91-20 and B-91-19) were conducted with cattle naturally-infested, and one pivotal study (B-92-5) was conducted with cattle with experimentally-infested with migrating larval stages of the common cattle grub, Hypoderma lineatum. Study number B-91-19 is reported as a clinical field trial in this FOI summary. These studies contained a combined total of 97 control animals of which 77 were infested with H. lineatum larvae and a combined total of 179 treated animals of which no animals were positive for H. lineatum larvae.

These trials demonstrated that the proposed recommended dose for moxidectin 0.5% pour-on of 0.5 mg moxidectin/kg body weight was safe and highly effective against migrating larval stages of both H. bovis and H. lineatum.

Individual Dose Confirmation Studies

Study Number B-93-4

1. Type of Study: Dose confirmation study in cattle with naturally-acquired lice infestations.

2. Investigator: J. E. Lloyd, Ph.D.
University of Wyoming
Laramie, WY

3. General Design:

a. Purpose: This study was designed to confirm the effective dose required for control of lice infestations in cattle.

b. Animals: Twenty-four mixed breed beef cattle, weighing between 187 and 287 kg, were randomly assigned to treatment groups (eight/group) based on pretreatment counts of total adult and nymphal Solenopotes capillatus.

c. Housing: Following treatment cattle were maintained in outdoor pens by treatment group (eight animals/pen) and exposed to ambient weather conditions.

d. Infestation: All cattle had naturally-acquired lice infestations.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 0.5 or 1 mL/10 kg body weight providing 0.25 or 0.5 mg moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Lice counts conducted for 55 days

j. Pertinent Parameters Measured: Lice were counted from eight predilection sites on each individual animal at weekly intervals for eight weeks posttreatment.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following tables.

Lice Counts and % Reduction of adult and nymphal lice on cattle by moxidectin pour-on applied at 0.25 or 0.5 mg moxidectin /kg

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number B-91-24

1. Type of Study: Dose confirmation study in cattle with naturally-acquired lice and grub infestations.

2. Investigator: L. L. Smith, D.V.M.
Larry Smith Research and Development, Inc.
Lodi, WI

3. General Design:

a. Purpose: This study was designed to confirm the effective dose required for control of lice and grub infestations in cattle.

b. Animals: Forty beef breeds and beef-cross breeds, weighing between 158 and 332 kg, were randomly assigned to treatment groups (twenty/group) based on pretreatment counts of Haematopinus eurysternus.

c. Housing: Following treatment cattle were maintained in a loose-pen barn with outdoor pens by treatment group (twenty animals/pen) and exposed to ambient weather conditions.

d. Infestation: All cattle had naturally-acquired lice and grub infestations.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Lice counts for 56 days and warble counts throughout an 85 day period.

j. Pertinent Parameters Measured: Lice were counted from eight predilection sites on each individual animal at weekly intervals for eight weeks posttreatment. Warbles were counted and grubs identified at weekly intervals from Day 21 to Day 85 posttreatment.

4. Results: Efficacy data for parasites present in a minimum of six control animals are given in the following table. Efficacy was demonstrated against adult and nymphal stages of both lice species present. A total of nine of the 20 control animals were infested with the cattle grub, Hypoderma bovis. The infested cattle had an average of 8.7 grubs while no grubs were found in any of the treated animals at any time during the study.

Lice Counts and % Reduction of adult and nymphal Haematopinus eurysternus and Bovicola bovis by moxidectin pour-on applied at 0.5 mg moxidectin /kg

% Reduction of Hypoderma bovis by moxidectin pour-on applied at 0.5 mg moxidectin /kg

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number B-91-20

1. Type of Study: Dose confirmation study in cattle with naturally-acquired lice and grub infestations.

2. Investigator: J.E. Lloyd, Ph.D.
University of Wyoming
Laramie, WY

3. General Design:

a. Purpose: This study was designed to evaluate the dose required for effective control of cattle grub infestations in cattle.

b. Animals: Eighty crossbred beef steers, weighing between 160 and 273 kg, were randomly assigned to treatment groups (40 animals/group) based on pretreatment body weights.

c. Housing: Following treatment cattle were maintained in outdoor pens by treatment group (eight animals/pen) and exposed to ambient weather conditions.

d. Infestation: All cattle had naturally-acquired grub infestations.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Grub counts throughout a 191 day experimental period.

j. Pertinent Parameters Measured: Cattle were manually palpated for warbles for approximately six months while grubs were emerging in the back of cattle. Third instar larvae were identified to species using a fiber optic light while encysted in the backs of animals.

4. Results: All 40 control animals were positive for both Hypoderma bovis and Hypoderma lineatum. A total of three, third instar H. bovis were found in one of the moxidectin pour-on treated animals.

% Reduction of Hypoderma bovis by moxidectin pour-on
applied at 0.5 mg moxidectin /kg

% Reduction of Hypoderma lineatum by moxidectin pour-on
applied at 0.5 mg moxidectin /kg

5. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number B-92-5

1. Type of Study: Dose confirmation study in cattle with experimentally-induced grub infestations.

2. Investigators: J. A. Miller, Ph.D. and P. J. Scholl, Ph.D.
USDA-ARS
US Livestock Insects Research Laboratory
Kerrville, TX

3. General Design:

a. Purpose: This study was designed to confirm the efficacy and safety, relative to treatment timing, of moxidectin pour-on for grub infestations in cattle.

b. Animals: Thirty-two Hereford and Hereford cross calves, weighing between 125 and 225 kg were used. Animals were randomly assigned to four treatment groups (eight animals/group) on the basis of KELISA values, indicative of exposure to Hypoderma lineatum larvae, and fecal nematode egg counts.

c. Housing: Animals were stanchioned during the controlled infestations and for observation during a 21 day period following treatment. The cattle were maintained on common pasture when not stanchioned.

d. Infestations: Each animal was experimentally-infested with 50 infective Hypoderma lineatum larvae over an approximate one month period (Feb. 17 to Mar. 21). Following this procedure, cattle grazed pastures where they acquired natural nematode infections.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once in June to calves at 0.5 mL/10 kg body weight providing 0.25 mg moxidectin/kg body weight.

Moxidectin 0.5% pour-on was applied once in June to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

Moxidectin 0.5% pour-on was applied once in August to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

Treatment date - June treatment was considered appropriate treatment timing and August was considered late season treatment based on the life cycle of the common cattle grub. The late season treatment occurred when larvae were expected to be migrating through the esophageal tissues.

h. Controls: Pour-on vehicle (no moxidectin) applied on both treatment dates to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Warble counts at various times throughout a 221 day test period.

j. Pertinent Parameters Measured: Cattle were manually palpated for warbles starting October 8, and continuing until all animals were negative for warbles for two consecutive weeks (Feb 5).

4. Results: Seven out of eight control animals were infested with Hypoderma lineatum. No warbles were palpated in any treated animal during the test period. Efficacy compared to peak control values is as follows:

Efficacy of moxidectin pour-on (mg/kg) against H. lineatum

5. Adverse Reactions: No adverse reactions to treatment were observed with either normal or late season treatment.

Horn Fly Dose Confirmation Studies

The efficacy of the recommended dose of moxidectin pour-on in reducing adult horn fly populations on treated cattle was confirmed in two studies. One study, conducted under confined conditions, clearly demonstrated the activity of the product against horn flies. A second study demonstrated efficacy in a cow-calf herd maintained under field conditions.

Study Number B-92-16

1. Type of Study: Dose confirmation study against Haematobia irritans (horn fly) under confined conditions.

2. Investigator: B. C. Clymer, Ph.D.
CAVL, Inc. and CRC
Amarillo, TX

3. General Design:

a. Purpose: This study was designed to confirm the effective dose for control of horn flies on cattle under confined conditions.

b. Animals: This study used 12 Hereford steers, weighing between 247 and 304 kg. It was determined which six animals produced feces with the highest pupation following seeding with horn fly eggs (principals) and these animals were randomly assigned to the control or treated groups. The remaining six animals (alternates) were also randomly assigned to the control or treated groups. All principal and alternate animals were treated on Day 0. Alternate animals were available to replace a principal animal if necessary for health reasons.

c. Housing: Each principal animal was kept in a stanchion within an individual environmentally controlled room. Alternate animals were housed by treatment group in outdoor pens which were partially covered with a roof.

d. Infestation: Pupae and adult flies from a fly colony were added to environmentally controlled rooms to establish the fly populations. Additional pupae were added to the rooms every two to three days to repopulate the rooms with flies.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to cattle at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to cattle at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: 63 days posttreatment.

j. Pertinent Parameters Measured: Horn flies on each animal were counted twice a week until Day 63. Total fecal collections were done and effects on pupation and horn fly emergence were evaluated.

4. Results: On Day 0 the control group mean horn fly count was 1029.9 and the treated group mean was 1463.6. Moxidectin pour-on effectively reduced adult horn fly counts during the posttreatment period. Moxidectin treatment did not affect pupation or adult fly emergence in this study.

% Reduction of Haematobia irritans on steers treated with moxidectin pour-on applied at 0.5 mg moxidectin /kg

5. Adverse Reactions: No adverse reactions to treatment were observed. Two control animals were replaced during the study due to bloat.

Study Number B-93-17

1. Type of Study: Dose confirmation study using cattle with naturally-acquired Haematobia irritans (horn fly) infestations.

2. Investigator: H. J. Meyer, Ph.D.
North Dakota State University
Fargo, ND

3. General Design:

a. Purpose: This study was designed to confirm the effective dose for control of horn flies on cattle under field conditions.

b. Animals: This study used 44 Gelbvieh and Angus breed beef cows, weighing between 481 and 686 kg. All cows were nursing a calf ranging in weight from 102 to 230 kg. The cow-calf pairs were assigned to one of two pastures (22 per pasture) based on cow age, calf sex, calf age, and sire of the calf. One pasture was randomly assigned to the treated group and one pasture to the control group.

c. Housing: The two groups of cow-calf pairs were maintained on two centrally-located adjacent pastures at the Central Grasslands Research Station in Streeter, ND.

d. Infestation: Cattle were naturally infested with horn flies.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to cows and calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight. Calves were treated to avoid the possible creation of a reservoir for horn flies within the treated herd. Horn fly counts on calves were not taken or used in the evaluation.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to cows at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight. Calves were treated at the same dose rate as their dams which was necessary to maintain the blinding of the study personnel as to treatment identity.

i. Test Duration: 42 days posttreatment.

j. Pertinent Parameters Measured: Horn flies on one entire side of each animal were counted pretreatment and at weekly intervals for six weeks posttreatment.

4. Results: Moxidectin pour-on effectively reduced fly counts for at least seven days posttreatment. At 14 days posttreatment there was no difference between the groups and there was also a noticeable drop in the fly population in the control herd. This drop may have been due to the influence of the treated herd, in an adjacent pasture, on fly populations affecting both the treated and control pastures.

% Reduction of Haematobia irritans on cows treated with moxidectin pour-on applied at 0.5 mg moxidectin /kg

5. Adverse Reactions: No adverse reactions to treatment were observed.

C. Clinical Field Studies

Six field studies were conducted at various locations throughout the United States. Five of these studies (four pasture studies and one feedlot) evaluated the efficacy and safety of the final commercial formulation of moxidectin 0.5% pour-on using cattle with naturally acquired nematode infections. An additional study was conducted to evaluate efficacy and safety using cattle naturally infested with the common cattle grub, Hypoderma lineatum.

Field Efficacy Against Endoparasites - Pasture Studies

1. Type of Study: Four pivotal field clinical studies (Study Numbers 0863-B-US-9-96, 0863-B-US-11-96, 0863-B-US-12-96, 0863-B-US-13-96) were conducted under pasture management conditions using cattle with naturally-acquired nematode infections.

2. Investigators:

3. General Design:

a. Purpose: These studies were designed to confirm the effectiveness and safety of the recommended dose of moxidectin pour-on when used under pasture conditions for the control of endoparasites in cattle.

b. Animals: At each study site approximately 100 animals were treated with moxidectin 0.5% pour-on and approximately 50 animals were treated with pour-on vehicle. As a result of the unequal numbers of treated and control cattle it was necessary to divide them into three groups of fifty animals each in order to blind the study personnel. Cattle were assigned to one of the three groups on the basis of two pretreatment fecal egg counts. Fifty blocks of three animals each were created and a random number was assigned to each animal. The random numbers were used to assign cattle to one of three groups (control and two treated groups).

Summary information for cattle treated with moxidectin 0.5% pour-on at each study site.

c. Housing: All cattle were maintained on pasture throughout the studies. In two studies (0863-B-US-12-96 and 0863-B-US-13-96), cattle were maintained on three separate pastures by treatment group. In one study (0863-B-US-9-96), as the result of local management practices, cattle were divided into separate pastures by sex without regard for treatment group assignment. In the final study, cattle from two nearby farms were used, steers and heifers on both farms were mixed with no treatment group separation.

d. Infection: Cattle had naturally-acquired nematode infections.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to cattle at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to cattle at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Final fecal egg counts at 21 days posttreatment

j. Pertinent Parameters Measured: Individual animal fecal samples were examined pretreatment and posttreatment using a flotation procedure in all four studies.

4. Results: The results of fecal nematode egg count reductions are summarized in the following table.

Arithmetic means of fecal strongylate egg counts (EPG) in vehicle treated control and moxidectin 0.5% pour-on treated cattle and percent efficacy of moxidectin 0.5% pour-on.

5. Adverse Reactions: No adverse reactions to treatment or pour-on site reactions were observed in any animal at any of the four study sites.

Field Efficacy Against Endoparasites - Feedlot Study

Study Number B-93-13

1. Type of Study: This was a pivotal field clinical study conducted under feedlot management conditions using cattle with naturally-acquired nematode infections.

2. Investigator: J. N. Davidson, D.V.M., M.P.V.M
Health Management Services
Tulare, CA

3. General Design:

a. Purpose: This study was designed to confirm the effectiveness and safety of the recommended dose of moxidectin pour-on when used under field conditions for the control of endoparasites in cattle.

b. Animals: This study used a total of 100 crossbred beef steers and heifers, weighing between 138 and 297 kg at trial initiation. Animals were randomly assigned to the moxidectin treated or control group (50 animals/group) based on total EPG counts.

c. Housing: Following treatment cattle were maintained in outdoor pens by treatment group and exposed to ambient weather conditions.

d. Infection: Cattle had naturally-acquired nematode infections.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to cattle at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to cattle at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Final fecal samples for EPG counts were taken at 56 days posttreatment.

j. Pertinent Parameters Measured: Individual animal fecal samples were examined pretreatment and posttreatment using a modified McMaster procedure.

4. Results: The results of fecal nematode egg count reductions are summarized in the following table.

Arithmetic means of fecal trichostrongyle egg counts (EPG) in vehicle treated control and moxidectin 0.5% pour-on treated cattle and percent efficacy of moxidectin 0.5% pour-on.

5. Adverse Reactions: No adverse reactions to treatment or pour-on site reactions were observed in any animal.

Field Efficacy Against Cattle Grubs

Study Number B-91-19

1. Type of Study: Field Clinical study in cattle with naturally-acquired grub infestations.

2. Investigator: J. B. Campbell, Ph.D.
University of Nebraska
North Platte, NE

3. General Design:

a. Purpose: This study was designed to confirm the effective dose for control of cattle grubs under field conditions in cattle.

b. Animals: This study used 175 four-way crossbred heifers, weighing between 115 and 255 kg, that were randomly allocated to either the control group (50 animals) or the treated group (125 animals).

c. Housing: All cattle were maintained on pasture at a commercial ranch in Dunning, NE on which cattle had a history of grub infestations. After treatment and until Day 60 posttreatment, control and moxidectin treated cattle were grazed in two separate pastures. From Day 60 to trial termination, all cattle were combined and maintained on a common pasture.

d. Infestation: Cattle had naturally-acquired cattle grub infestations.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on was applied once on Day 0 to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

h. Controls: Pour-on vehicle (no moxidectin) was applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: Treatment took place in October and warbles were counted the following February and March (152 days posttreatment).

j. Pertinent Parameters Measured: Warbles were palpated and grubs collected for identification at 120 and 152 days posttreatment.

4. Results: On Day 120 posttreatment, 30 of the control animals were positive for grubs and nine control animals were positive on Day 152. All grubs collected for identification were determined to be the common cattle grub, Hypoderma lineatum. No grubs were palpated in any of the moxidectin pour-on treated cattle on either examination day.

5. Adverse Reactions: No adverse reactions to treatment were observed. One control animal died of pneumonia prior to the Day 120 palpation.

D. Effect of Weather on Efficacy

A total 29 pivotal efficacy studies are summarized in this document, of which in 19 studies the cattle were maintained outdoors exposed to ambient weather conditions during the posttreatment period. These studies were conducted during all seasons of the year in variety of geographical locations. Cattle were exposed from weather conditions ranging from bright sunshine to cold snowy conditions. As a result, the efficacy of moxidectin 0.5% pour-on was demonstrated a spectrum of real world weather conditions. Two pivotal studies were conducted to specifically determine the potential effect of rainfall on the efficacy of moxidectin pour-on. In both studies rain was applied at a rate of 2 inches per hour. This rate was considered "worst-case", because it is equivalent to the mean maximum hourly rainfall in the United States (based on a U.S. Department of Interior Geological Survey). Both studies demonstrated that under the worst predicted U.S. rain conditions no effect on product efficacy would be expected.

Study Number B-92-13

1. Type of Study: Dose confirmation of efficacy against nematodes and the influence of rainfall on efficacy.

2. Investigator: B. C. Clymer, Ph.D.
CAVL, Inc. and CRC
Amarillo, TX

3. General Design:

a. Purpose: This study was designed to evaluate the potential effect of rainfall on the efficacy of moxidectin pour-on against gastrointestinal roundworms as determined by fecal egg counts.

b. Animals: Forty-eight mixed beef breed heifers, weighing between 179 and 250 kg, were randomly assigned to one of six treatment groups (eight animals/group) based on the average of the Day -3 and Day -2 fecal egg counts.

c. Housing: Following treatment cattle were maintained in outdoor pens by treatment group. Each pen had a roofed area in which animals could be confined if rain was imminent to avoid confounding the effect of simulated rain with natural rain. At all other times cattle were outdoors exposed to ambient weather conditions.

d. Infection: All cattle had naturally-acquired nematode infections.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on applied once to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight. The following five groups were treated with moxidectin pour-on and exposed to simulated rain for 30 minutes at a rate of 2 inches/hour:

• Moxidectin pour-on treatment and no rain exposure
• Moxidectin pour-on treatment and rain exposure prior to treatment
• Moxidectin pour-on treatment and rain exposure 2 hours posttreatment
• Moxidectin pour-on treatment and rain exposure 6 hours posttreatment
• Moxidectin pour-on treatment and rain exposure 24 hours posttreatment

h. Controls: Pour-on vehicle (no moxidectin) applied once to calves at 1 mL/10 kg body weight providing 0 mg moxidectin/kg body weight.

i. Test Duration: EPG evaluation for 21 days posttreatment.

j. Pertinent Parameters Measured: Individual animal fecal samples were examined pretreatment and posttreatment using a flotation procedure.

4. Results: Application of moxidectin pour-on at the recommended dose to wet cattle or to cattle exposed to heavy rainfall (2 inches/hour) at 2 to 24 hours posttreatment did not impair efficacy as determined by fecal output of nematode eggs. All moxidectin treatment reductions were different (P<0.05) from the untreated control animals. On Day 7, there was no effect of simulated rain either pre- or posttreatment. On Days 14 and 21, simulated rain prior to treatment, and at 2 and 24 posttreatment, was not different from the positive controls (treatment and no exposure to rain); however, the reduction of the group treated 6 hours posttreatment was less than the positive controls. This result was heavily skewed by the EPG count of one animal and is of questionable biological significance since rain at shorter and longer time intervals relative to treatment did not affect efficacy.

^a,b,c Means in the same column with different superscripts differ at P<0.05.

e. Adverse Reactions: No adverse reactions to treatment were observed.

Study Number 0863-B-US-4-95

1. Type of Study: Evaluation of the wash-off potential of moxidectin from cattle treated with moxidectin 0.5% pour-on and exposed to simulated rain.

2. Investigator: William Barton, Ph.D.
CAVL, Inc.
Amarillo, TX

3. General Design:

a. Purpose: This study was designed to quantify the amount of moxidectin which would be expected to wash-off from treated cattle following a heavy rain event (2 inches/hour).

b. Animals: Six mixed beef breed heifers, weighing between 196 and 236 kg, were randomly assigned to one of three treatment groups (two animals/group).

c. Housing: Following treatment, each animal was confined indoors in an individual pen. Cattle were held indoors to avoid any confounding effect of existing weather conditions on the simulated rain aspect of the study. Cattle were released to outdoor pens when the simulated rain was completed.

d. Infection: Not applicable, efficacy was not evaluated in this study.

e. Dosage Form: Moxidectin 0.5% pour-on, 5 mg/mL

f. Route of Administration: Topically along the back from the withers to the tailhead.

g. Doses: Moxidectin 0.5% pour-on applied once to calves at 1 mL/10 kg body weight providing 0.5 mg moxidectin/kg body weight.

There were three groups treated with moxidectin pour-on and exposed to simulated rain at one, two or six hours after treatment. Each animal was individually placed in an apparatus that was lined with stainless steel and allowed for total collection of the water applied to the animals. Rain was applied for 30 minutes at a rate of 2 inches/hour. When the simulated rain was completed and the animal removed, the apparatus was rinsed with methanol to remove any residual moxidectin which may have been bound to the walls of the apparatus.

h. Controls: None, one animal was placed in the apparatus and rinse samples were collected for analytical purposes. These samples were not used for statistical purposes.

i. Test Duration: All samples were collected on the day of treatment.

j. Pertinent Parameters Measured: The water and methanol rinses for each animal were assayed for moxidectin content.

4. Results: As a percentage of the moxidectin dose applied, the amount of moxidectin which washed-off at one, two and six hours posttreatment was 0.6, 0.71, and 1.49%. These values were not different from each other as determined with a protected LSD procedure. The mean amount of moxidectin which washed-off of all animals regardless of timing of rain was 0.93%. Under conditions of heavy rain (2 inches/hour), approximately 1% of the applied dose would be predicted to be washed-off. This minor amount will not affect the efficacy of the product.

5. Adverse Reactions: No adverse reactions to treatment were observed.

NADA 141-099 CYDECTIN® (moxidectin) 0.5% Pour-On for Cattle - original approval (continued)