Drug Trials Snapshots: TRULANCE
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 TRULANCE Prescribing Information for complete information.
TRULANCE (plecanatide)
(troo’ lans)
Synergy Pharmaceuticals, Inc.
Approval date: January 19, 2017
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
TRULANCE is used to treat a type of constipation called chronic idiopathic constipation (CIC) in adults.
“Idiopathic” means that the cause of the constipation is unknown.
How is this drug used?
TRULANCE is a tablet taken one time each day.
What are the benefits of this drug?
More patients who received TRULANCE experienced an increase in the number of complete spontaneous bowel movements (CSBMs) to at least 3 bowel movements per week than those who received placebo.
What are the benefits of this drug (results of trials used to assess efficacy)?
Patients who entered the trial had a history of chronic constipation which included having less than 3 bowel movements per week. 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 a least 3 CSBMs in a given week and an increase of at least 1 CSBM from baseline in the same week for at least 9 weeks out of the 12 week treatment period and at least 3 of the last 4 weeks of the study.
The table below summarizes efficacy results for the clinical trials based on the primary efficacy endpoint.
Table 2. Efficacy Responder Rates in the Two Placebo Controlled Trials of CIC: at least 9 of 12 weeks and at least 3 of the last 4 weeks (ITT Population)
| Trial 1 | |||
|---|---|---|---|
| TRULANCE N = 453 | Placebo N = 452 | Treatment Difference# [95% CI*] | |
| Responder^ | 21% | 10% | 11% [6.1%, 15.4%] |
| Trial 2 | |||
| TRULANCE N = 430 | Placebo N = 440 | Treatment Difference# [95% CI*] | |
| Responder^ | 21% | 13% | 8% [2.6%, 12.4%] |
* CI = confidence interval
^ primary endpoint defined as a patient who had a least 3 CSBMs in a given week and an increase of at least 1 CSBM from baseline in the same week for at least 9 weeks out of the 12 week treatment period and at least 3 of the last 4 weeks of the study
# p-value >
TRULANCE Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: TRULANCE worked similarly in men and women.
- Race: TRULANCE worked similarly in White and Black or African American patients. The number of patients in other races was limited; therefore, differences in response among all races could not be determined.
- Age: The number of patients above 65 years of age was limited; therefore, differences in response between patients above and below 65 years of age could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Tables below summarize efficacy results by subgroup for each trial based on ITT population.
Table 3. Results for the Primary Efficacy Endpoint by Sex, Age and Race, for Trial 1 (ITT population)
| Subgroup | TRULANCE (N=453) x/n (%) | Placebo (N=452) x/n (%) |
|---|---|---|
| Sex | ||
| Men | 15/85 (18) | 7/95 (7) |
| Women | 77/368 (21) | 38/357 (11) |
| Age Group (years) | ||
| 18-64 | 80/409 (20) | 39/405 (10) |
| ≥65 | 12/44 (27) | 6/47 (13) |
| Race | ||
| White | 62/302 (21) | 34/323 (11) |
| Black or African American | 27/129 (21) | 7/108 (7) |
| Asian | 2/13 (15) | 3/13/ (23) |
| American Indian or Alaska Native | 1/2 (50) | 0/0 |
| Native Hawaiian or Other Pacific Islander | 0/2 | 0/0 |
| Other | 0/5 | 1/8 (13) |
| Ethnicity | ||
| Hispanic or Latino | 32/112 (29) | 21/131 (16) |
| Not Hispanic or Latino | 60/341 (18) | 24/321 (8) |
Clinical trial data
Table 4. Results for the Primary Efficacy Endpoints by Sex, Age and Race, for Trial 2 (ITT population)
| Subgroup | TRULANCE (N=430) x/n (%) | Placebo (N=440) x/n (%) |
|---|---|---|
| Sex | ||
| Men | 17/95 (18) | 17/92 (19) |
| Women | 67/335 (20) | 40/348 (12) |
| Age Group (years) | ||
| 18-64 | 77/388 (20) | 52/386 (14) |
| ≥65 | 7/42 (17) | 5/54 (9) |
| Race | ||
| White | 62/329 (19) | 45/327 (14) |
| Black or African American | 19/88 (22) | 10/91 (11) |
| Asian | 1/7 (14) | 0/14 |
| American Indian or Alaska Native | 0/0 | 0/0 |
| Native Hawaiian or Other Pacific Islander | 0/0 | 1/3 (33) |
| Other | 2/6 (33) | 1/5 (20) |
| Ethnicity | ||
| Hispanic or Latino | 45/238 (19) | 40/251 (16) |
| Not Hispanic or Latino | 39/192 (20) | 17/189 (9) |
Clinical trial data
What are the possible side effects?
The most common side effect of TRULANCE is diarrhea and it can sometimes be severe.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes adverse reactions that occurred in clinical trials. Presented is the safety population that includes all patients who received at least one dose of the treatment.
Table 5: Most Common Adverse Reactions* in Two Placebo Controlled Trials of TRULANCE in Patients with CIC
| Adverse Reaction | TRULANCE (N = 863) % | Placebo (N = 870) % |
|---|---|---|
| Diarrhea | 5 | 1 |
* reported in at least 2% of TRULANCE-treated patients and at an incidence greater than placebo
TRULANCE 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: The risk of side effects was similar in White and Black or African American patients. The number of patients in other races was limited; therefore, differences in side effects among all races could not be determined.
- Age: The number of patients above 65 years of age was limited; therefore, differences in side effects between patients above and below 65 years of age could not be determined.
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 - (safety population)
| Subgroup | TRULANCE (N=863) x/n (%) | Placebo (N=870) x/n (%) |
|---|---|---|
| Sex | ||
| Men | 14/177 (8) | 8/181 (4) |
| Women | 82/686 (12) | 39/689 (6) |
| Age Group (years) | ||
| 18-64 | 85/777 (11) | 41/772 (5) |
| ≥65 | 11/86 (13) | 6/98 (6) |
| Race | ||
| White | 70/621 (11) | 34/634 (5) |
| Black or African American | 24/208 (12) | 9/193 (5) |
| Asian | 2/20 (10) | 3/27 (11) |
| American Indian or Alaska Native | 0/2 | 0/0 |
| Native Hawaiian or Other Pacific Islander | 0/2 | 0/3 |
| Other | 0/10 | 1/13 (8) |
| Ethnicity | ||
| Hispanic or Latino | 20/338 (6) | 14/365 (4) |
| Not Hispanic or Latino | 76/525 (15) | 33/505 (7) |
Clinical trial report
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved TRULANCE based on evidence from two clinical trials of 1733 patients with CIC. The trials were conducted in the USA and Canada.
The figure below summarizes how many men and women were in the clinical trials.
Figure 1. Baseline Demographics by Sex
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
Clinical trial data
Table 1. Baseline Demographics by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 1255 | 72 |
| Black or African American | 401 | 23 |
| Asian | 47 | 3 |
| America Indian or Alaska Native | 2 | less than 1 |
| Native Hawaiian or Other Pacific Islander | 5 | less than 1 |
| Other | 23 | 1 |
Clinical trial data
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trials.
Figure 3. Baseline Demographics by Age
Clinical trial data
Who participated in the trials?
The table below summarizes demographics of patients in the clinical trials.
Table 7. Baseline Demographics for Safety Population
Clinical trial data
How were the trials designed?
The benefit and side effects of TRULANCE were evaluated in two clinical trials of 1733 patients with CIC. In both trials patients received treatment with either TRULANCE 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 CSBMs over various periods of time.
How were the trials designed?
The efficacy and safety of TRULANCE for the management of symptoms of CIC was established in two 12-week, double blind, placebo-controlled, randomized, multicenter clinical trials in adult patients. Patients had to have specific constipation symptoms for at least 3 months prior to the screening visit, with symptom onset for at least 6 months prior to diagnosis.
A responder was defined as a patient who had a least 3 CSBMs in a given week and an increase of at least 1 CSBM from baseline in the same week for at least 9 weeks out of the 12 week treatment period and at least 3 of the last 4 weeks of the trial.
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.