Animal & Veterinary
NADA 141-062 Program® Cat Flavor Tabs™ - original approval
Approval Date: March 3, 1997
I. GENERAL INFORMATION:
| NADA | 141-062 |
| Sponsor: | Novartis Animal Health US, Inc. Animal Health Division Post Office Box 18300 Greensboro, NC 27419-8300 |
| Generic Name: | lufenuron |
| Trade Name: | Program® Cat Flavor Tabs™ |
| Marketing Status: | Over the Counter (OTC) |
II. INDICATIONS FOR USE
PROGRAM Cat Flavor Tabs are indicated for use in cats and kittens, six weeks of age and older, for the control of flea populations.
III. DOSAGE
| A. | DOSAGE FORM | Oral Tablets (Flavored) |
| B. | ROUTE OF ADMINISTRATION |
PROGRAM Cat Flavor Tabs may be administered as a treat, placed directly into the cat's mouth or broken and mixed into wet food. Give in conjunction with a full meal. In multi-cat households, cats should be separated during treatment to achieve adequate dosing in each cat. |
| C. | RECOMMENDED DOSAGES: |
PROGRAM Cat Flavor Tabs are given orally, once a month, at the recommended minimum dosage of 13.6 mg lufenuron per pound (30mg/kg) of body weight.
Recommended Dosage Schedule
---------------------------
Body Weight Lufenuron Per Tablet
------------- --------------------
Up to 10 lbs. 135 mg
11 to 20 lbs. 270 mg
Cats over 20 lbs are provided the appropriate combination of tablets.
|
IV. EFFECTIVENESS
Lufenuron is an insect development inhibitor which breaks the flea life cycle at the egg stage. The adult female flea is exposed to the drug when feeding on a treated cat. The drug, which has no deleterious effect on the adult flea, acts to inhibit the development of flea eggs. The mode of action is interference with the synthesis, polymerization and deposition of chitin, the major supportive component of the flea egg case and cuticle that forms the exoskeleton of larval stages.
A. Range-Finding Study in Cats to Determine Blood Levels of Lufenuron and Its Efficacy Against Adult Flea Emergence Using Different Dosage Forms of PROGRAM.
Purpose: PROGRAM Cat Flavor Tabs and PROGRAM Suspension were compared for flea control and changes in lufenuron blood levels
Investigator: Mark S. Holbert. B.S.
Study Location:
Stillmeadow, Inc.
Sugar Land, Texas
Type of Study: Experimental infestations of the cat flea, Ctenocephalides felis.
Animals: Eighteen adult domestic mixed breed cats, 9 males and 9 females, ranging in weight from 2.1 to 6.6 kg were used. The 18 animals were divided into 3 groups, 1 untreated control group of 6 animals and 2 treated groups of 6 animals each.
Dosage Forms:
Group 2: Lufenuron Cat Flavor Tabs
Group 3: Lufenuron Suspension, mixed with food
Route of Administration: Oral
Dose Tested: 30 mg/kg body weight
Frequency of Treatment: Once, on Day 0
Controls: Group 1: Untreated control group
Duration of Study: Cats were experimentally infested with 100 cat fleas on study Days -1, 11, and 24. The cats in groups 2 and 3 were treated with lufenuron on day 0. Flea eggs were collected from each cat on Days 5, 17, and 30. The number of adult fleas emerging from these eggs were counted 36 days after they were collected. Blood was collected on Days 1, 2, 4, 16, and 29 for analysis of lufenuron levels.
Results: Efficacy was calculated by comparing the development of eggs collected from fleas feeding on each of the 2 lufenuron-treated groups versus control animals. The following table shows the percent efficacy for each treatment group for each day eggs were collected.
Group Percent Efficacy Relative to
Control
--------------------------------------------
Day 5 Day 17 Day 30
----- ------ ------
2 99.4 100 99.3
3 84.7 62.2 91.1
The 90% and 95% confidence intervals were calculated on the difference between the percentage of eggs with non-emerging adults using the following pairwise comparisons:
Group I versus Group II (control vs flavor tablets),
Group I versus Group III (control vs suspension), and
Group II versus Group III (flavor tablets vs suspension).
The non-emergence rate for the treatment groups were:
Group I Control 0.4781 Group II Flavor Tablets 0.9978 Group III Suspension 0.8911
The 90% and 95% confidence intervals (CI) on the difference between treatment groups were:
Comparison 90% CI 95% CI --------------------- ------------ ------------ Group I vs Group II 0.500, 0.539 0.497, 0.543 Group I vs Group III 0.390, 0.436 0.386, 0.440 Group II vs Group III 0.094, 0.119 0.092, 0.121
The confidence bounds indicate that the flavor tablets and the suspension are not equivalent, and that cats treated the flavor tablets have higher incidence of flea non-emergence than cats treated with the suspension (i.e., the flavor tablets are "super" bioequivalent). Although not equivalent, the flavor tabs were more effective than the suspension in controlling flea emergence. Because these products were not compared for a determination of bioequivalence under the provisions of the Generic Animal Drug and Patent Term Restoration Act, but for a change in formulation with a different method of oral administration of the same product, this "super" bioequivalence is acceptable.
The following table shows the mean lufenuron concentrations.
Group Mean Lufenuron Concentration (SD) (ppb)
-----------------------------------------------
Day 1 Day 2 Day 4 Day 29
-------- -------- -------- ---------
2 710 366 373 191 289 112 188 75
3* 1320 297 967 307 634 141 392 121
*The data from one cat with levels below the limit of quantification
(50 ppb) were excluded
As shown in the table above, the higher clinical efficacy achieved by the flavor tabs was not due to higher blood levels of lufenuron. The group dosed with the suspension had higher mean lufenuron levels at every dosing period. Therefore, there is no safety concern with the "super" bioequivalence associated with the flavor tabs compared to the suspension.
Conclusions: PROGRAM Cat Flavor Tabs were more effective than PROGRAM suspension in controlling flea emergence.
This study indicates that PROGRAM Cat Tablets are "super" equivalent to PROGRAM Suspension, therefore the efficacy data provided in support of Novartis Animal Health's PROGRAM Suspension (NADA 141-026) can be used to support this approval. Refer to the Freedom of Information Summary for NADA 141-026 for additional information on efficacy studies conducted with PROGRAM Suspension.
Adverse Reactions: One cat in group 2 showed slight ocular irritation on day 30 of the study.
B. Flavored PROGRAM (Lufenuron) Tablets: Evaluation Palatability in Cats
Purpose: To evaluate the palatability of PROGRAM (lufenuron) Cat Flavor Tablets when administered orally to cats either free choice or by placing the tablet into the mouth and allowing the cat to chew
Investigators/Study Locations:
Jodi Black, DVM
Best Friends Veterinary Service
1328 Highway 65
Elkert, CO 81418
Mark Silvers, DVM
Cat Clinic of Greensboro
2138-B Lawndale Drive
Greensboro, NC 27408
Type of Study: Field palatability trial
Animals: 100 client owned cats with 98 completing the study and included in the analysis of palatability. Of these 98 cats, 51 were female and 47 were male.
Dosage Form: Oral tablet (flavored)
Route of Administration: The cat owners were instructed to dose the cat just prior to feeding by offering the tablet free choice from the hand, empty food dish or from the floor. If the cat didn't consume the tablet within 3 minutes the tablet was to be placed directly into the cat's mouth.
Dose Tested: Minimum of 30 mg/kg, according to the dosing scale
Frequency of Treatment: Once
Controls: None
Duration of Study: November 21 through December 9, 1995
Results: Of the 98 cats completing the study, 54 were successfully dosed for a 55% palatability rate.
Dosed Free Choice 37/98 38% Dosed in Mouth 17/98 17% ------------------------------- Total Dosed 54/98 55%
Conclusions: PROGRAM Cat Flavor Tablets are moderately palatable to cats, with a 55% acceptance rate.
Adverse Reactions: One cat developed lethargy and decreased appetite 1 day post treatment. On Day 3 post treatment, the cat's temperature was elevated at 105.0°F. The cat responded to treatment with antibiotics.
C. Flavored PROGRAM (Lufenuron) Tablets: Evaluation Dosage Form Acceptability in Cats
Purpose: To evaluate the dosage form acceptability of PROGRAM (lufenuron) Cat Flavor Tablets when administered orally to cats either free choice, manually, or broken and mixed with wet food.
Investigators/Study Locations:
Jodi Black, DVM
Best Friends Veterinary Service
1328 Highway 65
Elkert, CO 81418
Mark Silvers, DVM
Cat Clinic of Greensboro
2138-B Lawndale Drive
Greensboro, NC 27408
Type of Study: Field dosage form acceptability trial
Animals: 100 client owned cats with 91 completing the study and included in the analysis of acceptability. Of these 91 cats, 51 were male and 40 were female.
Dosage Form: Oral tablet (flavored)
Route of Administration: The cat owners were instructed to dose the cat just prior to feeding by offering the tablet free choice from the hand, empty food dish or from the floor. If the cat didn't consume the tablet within 3 minutes the tablet was to be placed directly into the cat's mouth. If dosing was still unsuccessful, the tablet was to be broken into a small portion of wet food.
Dose Tested: Minimum of 30 mg/kg, according to the dosing scale
Frequency of Treatment: Once
Controls: None
Duration of Study: January 18 through February 12, 1996
Results: Of the 91 cats completing the study, 82 were successfully dosed for a 90% acceptability rate.
Dosed Free Choice 29/91 32% Dosed in Mouth 34/91 37% Dosed in Food 19/91 21% ------------------------------- Total Dosed 82/91 90%
Conclusions: PROGRAM Cat Flavor Tablets are an acceptable dosage form for administration to cats, with a 90% acceptance rate.
Adverse Reactions: One cat vomited once 1 day post treatment and again 11 days post treatment.
V. ANIMAL SAFETY
Study A cited above indicates that PROGRAM Cat Flavor Tablets are "super" bioequivalent to PROGRAM Suspension. The superior efficacy of the flavor tablets were not due to increased blood levels of the drug, therefore the safety data provided in support of Novartis Animal Health's PROGRAM Suspension (NADA 141-026) can be used to support this approval. Refer to the Freedom of Information Summary for NADA 141-026 for additional information on target animal safety studies conducted with PROGRAM Suspension.
VI. HUMAN FOOD SAFETY:
Data on human safety, pertaining to consumption of drug residues in food, were not required for approval of this application. This drug is to be labeled for use in cats which are non-food animals.
VII. AGENCY CONCLUSIONS:
The data in support of this new animal drug application comply with the requirements of section 512 of the Federal Food, Drug, and Cosmetic Act and 514 of the implementing regulations. The data demonstrate that PROGRAM Cat Flavor Tabs (lufenuron), when used under labeled conditions of use, are safe and effective.
Because adequate directions for the safe and effective lay use of PROGRAM Cat Flavor Tabs could be written, the product has been labeled for over-the-counter distribution.
Under section 512(c)(2)(F)(ii) of the FFDCA, this approval for non food producing animals qualifies for THREE years of marketing exclusivity beginning on the date of approval because the application contains substantial evidence of the effectiveness of the drug involved, any studies of animal safety required for the approval of the application and conducted or sponsored by the applicant.
VIII. LABELING (Attached)
- Insert
- Blister Cards (6 Tablets)
- 135 mg
- 270 mg
- Bulk Package (60 Tablets)
- 135 mg
- 270 mg
- Dispensing Envelope
Copies of applicable labels may be obtained by writing to the:
Freedom of Information Office
Center for Veterinary Medicine, FDA
7500 Standish Place
Rockville, MD 20855
