Trial Outcomes & Findings for The Plecanatide Irritable Bowel Syndrome With Constipation Study (IBS-C) (NCT NCT02387359)
NCT ID: NCT02387359
Last Updated: 2019-06-14
Results Overview
An Overall Responder was a patient who was a Weekly Responder (i.e., decrease of 30% from baseline for abdominal pain intensity and an increase of at least one complete spontaneous bowel movement in the same week) for at least 6 of the 12 treatment weeks.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1054 participants
Primary outcome timeframe
12 Weeks
Results posted on
2019-06-14
Participant Flow
Participant milestones
| Measure |
Matching Placebo
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Overall Study
STARTED
|
354
|
351
|
349
|
|
Overall Study
COMPLETED
|
295
|
309
|
293
|
|
Overall Study
NOT COMPLETED
|
59
|
42
|
56
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The Plecanatide Irritable Bowel Syndrome With Constipation Study (IBS-C)
Baseline characteristics by cohort
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
Total
n=1054 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
43.0 years
STANDARD_DEVIATION 13.71 • n=93 Participants
|
43.0 years
STANDARD_DEVIATION 13.76 • n=4 Participants
|
43.2 years
STANDARD_DEVIATION 13.34 • n=27 Participants
|
43.1 years
STANDARD_DEVIATION 13.60 • n=483 Participants
|
|
Sex: Female, Male
Female
|
272 Participants
n=93 Participants
|
267 Participants
n=4 Participants
|
266 Participants
n=27 Participants
|
805 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
82 Participants
n=93 Participants
|
84 Participants
n=4 Participants
|
83 Participants
n=27 Participants
|
249 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: 12 WeeksAn Overall Responder was a patient who was a Weekly Responder (i.e., decrease of 30% from baseline for abdominal pain intensity and an increase of at least one complete spontaneous bowel movement in the same week) for at least 6 of the 12 treatment weeks.
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Number of Overall Responders - ITT Population
|
63 Participants
|
106 Participants
|
103 Participants
|
PRIMARY outcome
Timeframe: 12 WeeksAn Abdominal Pain Intensity Responder was a patient who had a decrease of 30% from baseline for abdominal pain intensity. Baseline was the mean of non-missing abdominal pain scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug.
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Number of Abdominal Pain Responders for at Least 6 of 12 Treatment Weeks
|
112 Participants
|
145 Participants
|
156 Participants
|
PRIMARY outcome
Timeframe: 12 weeksA Stool Frequency Responder is defined as a patient who experienced an increase of at least one CSBM (complete spontaneous bowel movement) per week from baseline. Baseline was the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug.
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Number of Stool Frequency Responder for at Least 6 of the 12 Treatment Weeks
|
124 Participants
|
169 Participants
|
157 Participants
|
SECONDARY outcome
Timeframe: 12 weeksA Sustained Efficacy Responder was a patient who was an Overall Responder who also was a Weekly Responder, i.e., decreased of 30% from baseline for abdominal pain intensity and increased of at least one CSBM (complete spontaneous bowel movement) in the same week for at least 2 of the 4 weeks in month 3 of the Treatment Period.
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Number of Sustained Efficacy Responders
|
61 Participants
|
99 Participants
|
96 Participants
|
SECONDARY outcome
Timeframe: Baseline and 12-WeekChange from baseline in stool consistency based upon the Bristol Stool Form Scale (BSFS) Rating 1 to 7. Baseline was the mean BSFS score recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. BSFS Rating 1 to 7: 1. Separate hard lumps, like nuts (hard to pass) 2. Sausage-shaped but lumpy 3. Like a sausage but with cracks on its surface 4. Like a sausage or snake, smooth and soft 5. Soft blobs with clear-cut edges (passed easily) 6. Fluffy pieces with ragged edges, a mushy stool 7. Watery, no solid pieces, entirely liquid
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Change From Baseline in Stool Consistency
Baseline
|
2.06 score on a scale
Standard Deviation 1.012
|
2.02 score on a scale
Standard Deviation 0.918
|
1.98 score on a scale
Standard Deviation 0.913
|
|
Change From Baseline in Stool Consistency
Week 12 change from baseline
|
1.06 score on a scale
Standard Deviation 1.357
|
1.59 score on a scale
Standard Deviation 1.592
|
1.86 score on a scale
Standard Deviation 1.593
|
SECONDARY outcome
Timeframe: Baseline and 12-weekChange from baseline in Straining Score over the 12-week treatment period. Baseline was the mean of non-missing straining scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The severity of straining during a bowel movement was measured using an 11-point scale (0-10 rating; 0 = no straining; 10 = worst straining).
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Change From Baseline in Straining
Baseline
|
6.39 score on a scale
Standard Deviation 1.991
|
6.47 score on a scale
Standard Deviation 1.828
|
6.50 score on a scale
Standard Deviation 1.822
|
|
Change From Baseline in Straining
Week 12 change from baseline
|
-1.87 score on a scale
Standard Deviation 2.464
|
-2.69 score on a scale
Standard Deviation 2.422
|
-2.88 score on a scale
Standard Deviation 2.464
|
SECONDARY outcome
Timeframe: Baseline and 12-WeekChange from baseline over the 12-week Treatment Period in CSBM (Complete Spontaneous Bowel Movement) Frequency Rate (CSBMs/Week). Baseline was the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug.
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Change From Baseline in CSBM Frequency Rate
Baseline
|
0.23 CSBMs per week
Standard Deviation 0.440
|
0.22 CSBMs per week
Standard Deviation 0.465
|
0.28 CSBMs per week
Standard Deviation 0.527
|
|
Change From Baseline in CSBM Frequency Rate
Week 12 change from baseline
|
0.86 CSBMs per week
Standard Deviation 1.904
|
1.46 CSBMs per week
Standard Deviation 2.565
|
1.41 CSBMs per week
Standard Deviation 2.586
|
SECONDARY outcome
Timeframe: Up to 24 hours after first dose of study drugNumber of patients with a SBM (spontaneous bowel movement) within 24 hours after the first dose of study drug
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Number of Patients With a SBM Within 24 Hours After the First Dose
|
118 Participants
|
168 Participants
|
175 Participants
|
SECONDARY outcome
Timeframe: Baseline and 12-WeekChange from baseline in abdominal pain as measured with an 11-point (0-10) Numerical Rating Scale from 0 (No) to 10 (Worst Possible). Baseline is the mean of non-missing abdominal pain scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug.
Outcome measures
| Measure |
Matching Placebo
n=354 Participants
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 Participants
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=349 Participants
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Change From Baseline in Abdominal Pain
Baseline
|
6.10 score on a scale
Standard Deviation 1.793
|
5.94 score on a scale
Standard Deviation 1.704
|
5.95 score on a scale
Standard Deviation 1.760
|
|
Change From Baseline in Abdominal Pain
Week 12 change from baseline
|
-1.79 score on a scale
Standard Deviation 2.196
|
-2.11 score on a scale
Standard Deviation 2.215
|
-2.46 score on a scale
Standard Deviation 2.370
|
Adverse Events
Matching Placebo
Serious events: 5 serious events
Other events: 16 other events
Deaths: 0 deaths
3.0 mg Plecanatide
Serious events: 4 serious events
Other events: 37 other events
Deaths: 0 deaths
6.0 mg Plecanatide
Serious events: 2 serious events
Other events: 28 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Matching Placebo
n=354 participants at risk
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 participants at risk
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=347 participants at risk
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Investigations
Transaminases increased
|
0.00%
0/354
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.28%
1/351 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.29%
1/347 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Investigations
Alanine aminotransferase increased
|
0.28%
1/354 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/351
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Investigations
Hepatic enzyme increase
|
0.28%
1/354 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/351
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Psychiatric disorders
Affective disorder
|
0.00%
0/354
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/351
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.29%
1/347 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Psychiatric disorders
Biplar I disorder
|
0.28%
1/354 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/351
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Psychiatric disorders
Psychotic disorder
|
0.28%
1/354 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/351
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Psychiatric disorders
Suicidal ideation
|
0.28%
1/354 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/351
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.00%
0/354
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.28%
1/351 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
General disorders
Drowning
|
0.00%
0/354
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.28%
1/351 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/354
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.28%
1/351 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Infections and infestations
Hepatitis C
|
0.00%
0/354
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/351
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.29%
1/347 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.28%
1/354 • Number of events 1
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/351
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.00%
0/347
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
Other adverse events
| Measure |
Matching Placebo
n=354 participants at risk
Placebo tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=351 participants at risk
Plecanatide 3.0 mg tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=347 participants at risk
Plecanatide 6.0 mg tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
2.0%
7/354 • Number of events 7
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
2.0%
7/351 • Number of events 7
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
1.2%
4/347 • Number of events 4
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Infections and infestations
Urinary tract infection
|
1.1%
4/354 • Number of events 4
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
1.1%
4/351 • Number of events 4
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
2.0%
7/347 • Number of events 7
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Gastrointestinal disorders
Diarrhea
|
0.56%
2/354 • Number of events 2
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
5.4%
19/351 • Number of events 20
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
4.3%
15/347 • Number of events 16
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
|
Gastrointestinal disorders
Nausea
|
0.85%
3/354 • Number of events 3
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
2.0%
7/351 • Number of events 7
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
0.58%
2/347 • Number of events 2
A total of 1054 patients were randomized, of which two patients did not receive the study drug (6 mg) and resulted in a total of 1052 patients in the Safety population.
|
Additional Information
VP Regulatory Affairs & Clinical QA
Synergy Pharmaceuticals Inc.
Phone: 646-675-7283
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place