Drugs

Drug Trials Snapshots: SYMPROIC

 

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to SYMPROIC Prescribing Information for complete information.

SYMPROIC (naldemedine)
(sim proe' ik)
Shionogi, Inc.
Approval date: March 23, 2017


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

SYMPROIC is used to treat adults with constipation caused by prescription pain drugs called opioids. It is to be used in patients who take opioids for long-lasting (chronic) pain that is not caused by cancer.

How is this drug used?

SYMPROIC is a tablet taken one time each day.

What are the benefits of this drug?

More patients who received SYMPROIC experienced an increase in the number of spontaneous bowel movements (SBMs) to at least 3 bowel movements per week in comparison to those who received placebo.

What are the benefits of this drug (results of trials used to assess efficacy)?

Efficacy was assessed using information provided by patients on a daily basis in an electronic diary. A responder was defined as a patient who had at least 3 SBMs per week and a change from baseline of at least 1 SBM per week for at least 9 out of the 12 study weeks and 3 out of the last 4 weeks for Trials 1 and 2.

The table below summarizes efficacy results for the clinical trials based on the primary efficacy endpoint.

Table 2. Efficacy Responder Rates in Trials 1 and 2 in Patients with OIC and Chronic Non-Cancer Pain (ITT Population)

 Trial 1Trial 2
SYMPROIC
(N=273)
Placebo
(N=272)
Treatment
Difference
[95% CI]
SYMPROIC
(N=276)
Placebo
(N=274)
Treatment
Difference
[95% Cl]
Responder#130 (48%)94 (35%)13%
[5%, 21%]
145 (53%)92 (34%)19%
[11%, 27%]
p value*  0.0020  <.0001

# the primary endpoint was defined as a patient who had at least 3 SBMs per week and a change from baseline of at least 1 SBM per week for at least 9 out of the 12 study weeks and 3 out of the last 4 weeks.
CI=Confidence Interval
* Cochran-Mantel-Haenszel test adjusted for opioid dose strata (30 to 100 mg; greater than 100 mg)

SYMPROIC Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: SYMPROIC worked similarly in men and women.
  • Race: Majority of the patients were White. The number of patients in other races was limited; therefore, differences in response among races could not be determined.
  • Age: SYMPROIC worked similarly in patients above and below 65 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Table below summarize efficacy results by subgroup for Trials 1 and 2 based on Intent-to treat (ITT) population.

Table 3. Proportion of Responders by Sex, Race, Age, and Geographic Region Subgroups

 Trial 1Trial 2
SYMPROICPlaceboSYMPROICPlacebo
Sex
Men55% (62/112)35% (36/104)57% (63/111)40% (42/106)
Women42% (68/161)35% (58/168)50% (82/165)30% (50/168)
Race
White47% (102/216)33% (73/220)55% (121/222)31% (71/227)
Black49% (26/53)42% (20/48)41% (20/49)46% (18/39)
Age Group
< 65 years49% (114/234)36% (80/225)51% (118/232)31% (74/236)
≥65 years41% (16/39)30% (14/47)61% (27/44)47% (18/38)
Region
US45% (104/230)35% (80/229)54% (130/241)33% (78/239)
Non-US61% (26/43)33% (14/43)43% (15/35)40% (14/35)

Adapted from FDA Statistical review

What are the possible side effects?

SYMPROIC may cause serious side effect including tear (perforation) in gut wall and opioid withdrawal.

The most common side effects of SYMPROIC are belly pain, diarrhea, and nausea.

What are the possible side effects?

The table below summarizes adverse reactions that occurred in clinical Trials 1 and 2. Presented is the safety population that includes all patients who received at least one dose of the treatment.

Table 4: Common Adverse Reactions* in Patients with OIC and Chronic Non-Cancer Pain (12-week data from Trials 1 and 2)

Adverse ReactionSYMPROIC
N=542
Placebo
N=546
Abdominal pain**8%2%
Diarrhea7%2%
Nausea4%2%
Gastroenteritis2%1%

*Adverse reactions occurring in at least 2% of patients receiving SYMPROIC and at an incidence greater than placebo.
**Abdominal pain includes Abdominal discomfort, Abdominal pain, Abdominal pain lower, Abdominal pain upper, Gastrointestinal pain

Table 5: Common Adverse Reactions* in Patients with OIC and Chronic Non-Cancer Pain (12-week data from Trial 3)

Adverse ReactionSYMPROIC
N=621
Placebo
N=619
Abdominal pain**11%5%
Diarrhea7%3%
Nausea6%5%
Vomiting3%2%
Gastroenteritis3%1%

*Adverse reactions occurring in at least 2% of patients receiving SYMPROIC and at an incidence greater than placebo.
**Abdominal pain includes Abdominal discomfort, Abdominal pain, Abdominal pain lower, Abdominal pain upper

SYMPROIC Prescribing Information

Were there any differences in side effects among sex, race and age?

  • Sex: The risk of side effects was similar in men and women.
  • Race: Majority of the patients were White. The number of patients in other races was limited; therefore, differences in side effects among races could not be determined.
  • Age: The risk of side effects was similar in patients above and below 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes subgroups of patients who reported any gastrointestinal adverse event during clinical trials.

Table 6. Subgroup Analysis of Gastrointestinal AEs - (pooled safety population; 12-week data from Trials 1, 2 and 3)

SubgroupSYMPROIC
(N=1163)
x/n (%)
Placebo
(N=1165)
x/n (%)
Sex
Men84/458 (18)50/427 (12)
Women169/705(24)111/738 (15)
Age Group (years)
< 65216/980 (22)135/1004 (13)
≥6537/183 (20)26/161 (16)
Race
White210/924 (23)139/943 (15)
Black or African American39/221 (18)20/195 (10)
Ethnicity
Hispanic or Latino20/338 (6)14/365 (4)
Not Hispanic or Latino76/525 (15)33/505 (7)

x/n= number of patents with at least one treatment-emergent adverse event (x) in the subgroup (n)
Clinical trial report

WHO WAS IN THE CLINICAL TRIALS?

Who participated in the clinical trials?

The FDA approved SYMPROIC based on evidence from three clinical trials of 2336 patients with OIC. The trials were conducted in the USA, Canada, Europe and Asia.

The figure below summarizes how many men and women were in the clinical trials.

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trials of the drug SYMPROIC . In total, 889 men (38%) and  1447 (62%) participated in the clinical trials.

Clinical trial data

Figure 2 and Table 1 below summarize the percentage of patients by race in the clinical trials.

Figure 2. Baseline Demographics by Race

Pie chart summarizing the percentage of patients by race in SYMPROIC clinical trials. In total, 1874 Whites (80%), 20 Asians (1%), 417 African Americans  (18%), and 25 Other (1%), participated in the clinical trials.

Clinical trial data

Table 1. Baseline Demographics by Race

RaceNumber of PatientsPercentage
White187480
Black or African American41718
Asian201
American Indian or Alaska Native181
Native Hawaiian or Other Pacific Islander7less than 1

Clinical trial data

Figure 3 summarizes the percentage of patients by age enrolled in the clinical trials.

Figure 3. Baseline Demographics by Age

Pie charts summarizing how many individuals of certain age groups were in the clinical trials. In total, 1990 were younger than 65 years (85%), and  346 patients (15%)were  65 years and older (52 %)

Clinical trial data

Who participated in the trials?

The table below summarizes demographics of enrolled patients in the clinical trials.

Table 7. Baseline Demographics of Participants in the Clinical Trials 1 and 2 (ITT population)

 Trial 1Trial 2
SYMPROIC N=273Placebo N=272SYMPROIC N=276Placebo N=274

Age (years):
  Mean (SD)


53.3 (10.4)

53.4 (11.0)

54.1 (10.5)

52.9 (11.4)
Age Group
  < 65 years234 (85.7%)225 (82.7%)232 (84.1%)236 (86.1%)
  ≥65 years39 (14.3%)47 (17.3%)44 (15.9%)38 (13.9%)
Sex
  Men112 (41.0%)104 (38.2%)111(40.2%)106 (38.7%)
  Women161 (59.0%)168 (61.8%)165 (59.8%)168 (61.3%)
Race
  White216 (79.1%)220 (80.9%)222 (80.4%)227 (82.8%)
  Black or African American53 (19.4%)48 (17.6%)49 (17.8%)39 (14.2%)
  Asian2 (0.7%)1 (0.4%)2 (0.7%)3 (1.1%)
  American Indian or Alaska Native1 (0.4%)1 (0.4%)3 (1.1%)4 (1.5%)
  Native Hawaiian or Other Pacific Islander1 (0.4%)2 (0.7%)01 (0.4%)
Ethnicity
  Hispanic or Latino26 (9.5%)27 (9.9%)26 (9.4%)27 (9.9%)
  Not Hispanic or Latino247 (90.5%)245 (90.1%)250 (90.6%)247 (90.1%)

Adapted from FDA Statistical review

Table 8. Baseline Demographics for Population in Trial 3 (ITT population)

 SYMPROIC N=621Placebo N=620
Age (years):
Mean (SD)

53.4 (11.7)

52.7 (10.5)
Age Group
  <65 years519(83.6%)544 (87.7%)
  ≥65 years102 (16.4)76 (12.3)
Sex
  Men238 (38%)218 (35%)
  Women383 (62%)402 (65%)
Race
  White492 (79.2%)497 (80.2%)
  Black or African American120 (19.3%)108 (17.4%)
  Asian5 (0.8%)7 (1.1%)
  American Indian or Alaska Native2 (0.3%)7 (1.1%)
  Native Hawaiian or Other Pacific Islander2 (0.3%)1 (0.2%)
Ethnicity
  Hispanic or Latino47 (7.6)%42 (6.8%)
  Not Hispanic or Latino574 (92.4%)578 (93.2%)

Adapted from FDA Statistical review

How were the trials designed?

The benefit and side effects of SYMPROIC were evaluated in three clinical trials of patients with OIC.

In Trials 1 and 2 patients received treatment with either SYMPROIC or placebo once daily for 12 weeks. Neither the patients nor the health care providers knew which treatment was being given until after the trials were completed.

Based on the information from their electronic diaries, patients were evaluated for improvement in SBMs over 12 weeks of treatment and for side effects.

In Trial 3, patients were allowed to continue their old treatment for constipation. In addition, they also received new treatment with either SYMPROIC or placebo once daily for 52 weeks. Neither the patients nor the health care providers knew which new treatment was being given until after the trials were completed. Patients were evaluated primarily for side effects.

How were the trials designed?

There were three clinical trials used for SYMPROIC evaluation.

The safety and efficacy of SYMPROIC were primarily established in 2 randomized, double-blind, placebo-controlled trials of 12 weeks duration in which SYMPROIC was used without laxatives in patients with OIC and chronic non-cancer pain.

All patients were on stable dose of opiates for at least 4 weeks prior to enrollment.

The primary efficacy outcome measure was the proportion of participants who achieved at least 3 SBMs per week and an increase from baseline of at least 1 SBM per week for at least 9 out of the 12 study weeks and 3 out of the last 4 weeks for Trials 1 and 2.

Trial 3 was a 52-week randomized clinical trial where patients were allowed to continue using their laxative regimen throughout the trial duration. The primary purpose of the trial was safety evaluation.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

PRESCRIBING INFORMATION

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Page Last Updated: 04/05/2017
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