Trial Outcomes & Findings for Second Plecanatide Study In Irritable Bowel Syndrome With Constipation (IBS-C) (NCT NCT02493452)
NCT ID: NCT02493452
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 1 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
1135 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
|
379
|
377
|
379
|
|
Overall Study
COMPLETED
|
329
|
328
|
325
|
|
Overall Study
NOT COMPLETED
|
50
|
49
|
54
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Second Plecanatide Study In Irritable Bowel Syndrome With Constipation (IBS-C)
Baseline characteristics by cohort
| Measure |
Matching Placebo
n=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 Participants
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
Total
n=1135 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
44.8 years
STANDARD_DEVIATION 14.68 • n=5 Participants
|
44.0 years
STANDARD_DEVIATION 14.61 • n=7 Participants
|
43.1 years
STANDARD_DEVIATION 14.20 • n=5 Participants
|
44.0 years
STANDARD_DEVIATION 14.50 • n=4 Participants
|
|
Sex: Female, Male
Female
|
272 Participants
n=5 Participants
|
270 Participants
n=7 Participants
|
273 Participants
n=5 Participants
|
815 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
107 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
106 Participants
n=5 Participants
|
320 Participants
n=4 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 1 complete spontaneous bowel movement in the same week) for at least 6 of the 12 treatment weeks.
Outcome measures
| Measure |
Matching Placebo
n=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 Participants
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Number of Overall Responders - ITT Population
|
54 Participants
|
81 Participants
|
91 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 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=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 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
|
88 Participants
|
123 Participants
|
129 Participants
|
PRIMARY outcome
Timeframe: 12 WeeksA Stool Frequency Responder was 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=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 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
|
106 Participants
|
129 Participants
|
148 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=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 Participants
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Number of Sustained Efficacy Responders
|
53 Participants
|
78 Participants
|
90 Participants
|
SECONDARY outcome
Timeframe: Baseline and 12-WeekChange from baseline in stool consistency based upon the Bristol Stool Form Scale (BSFS). 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=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 Participants
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Change From Baseline in Stool Consistency
Baseline
|
1.99 score on a scale
Standard Deviation 1.029
|
1.91 score on a scale
Standard Deviation 0.902
|
1.86 score on a scale
Standard Deviation 0.912
|
|
Change From Baseline in Stool Consistency
Week 12 change from baseline
|
1.04 score on a scale
Standard Deviation 1.579
|
1.55 score on a scale
Standard Deviation 1.631
|
1.45 score on a scale
Standard Deviation 1.621
|
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=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 Participants
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Change From Baseline in Straining
Week 12 change from baseline
|
-1.66 score on a scale
Standard Deviation 2.149
|
-2.35 score on a scale
Standard Deviation 2.540
|
-2.35 score on a scale
Standard Deviation 2.556
|
|
Change From Baseline in Straining
Baseline
|
6.75 score on a scale
Standard Deviation 1.848
|
6.84 score on a scale
Standard Deviation 1.860
|
6.87 score on a scale
Standard Deviation 1.920
|
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=376 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=375 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 Participants
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Change From Baseline in CSBMs (CSBMs/Week)Complete Spontaneous Bowel Movement
Baseline
|
0.24 CSBMs per week
Standard Deviation 0.465
|
0.26 CSBMs per week
Standard Deviation 0.530
|
0.27 CSBMs per week
Standard Deviation 0.527
|
|
Change From Baseline in CSBMs (CSBMs/Week)Complete Spontaneous Bowel Movement
Week 12 change from baseline
|
0.80 CSBMs per week
Standard Deviation 1.779
|
1.23 CSBMs per week
Standard Deviation 2.303
|
1.63 CSBMs per week
Standard Deviation 3.042
|
SECONDARY outcome
Timeframe: Up to 24 hours after the first dose of study drugA responder was any patient with a SBM within 24 hours after the first dose of study drug.
Outcome measures
| Measure |
Matching Placebo
n=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 Participants
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Number of Patients With a SBM Within 24 Hours After First Dose of Study Medication
|
119 Participants
|
157 Participants
|
167 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 (None) to 10 (Worst Possible). Baseline was the mean of the non-missing abdominal pain scores recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The average daily abdominal pain score was the average of the non-missing worst daily abdominal pain scores (on a 0 to 10 scale) in the given week.
Outcome measures
| Measure |
Matching Placebo
n=379 Participants
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=377 Participants
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 Participants
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Change From Baseline in Abdominal Pain
Baseline
|
6.40 score on a scale
Standard Deviation 1.624
|
6.56 score on a scale
Standard Deviation 1.634
|
6.48 score on a scale
Standard Deviation 1.714
|
|
Change From Baseline in Abdominal Pain
Week 12 change from baseline
|
-1.42 score on a scale
Standard Deviation 2.116
|
-2.00 score on a scale
Standard Deviation 2.226
|
-1.87 score on a scale
Standard Deviation 2.297
|
Adverse Events
Matching Placebo
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
3.0 mg Plecanatide
Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths
6.0 mg Plecanatide
Serious events: 3 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Matching Placebo
n=376 participants at risk
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=375 participants at risk
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 participants at risk
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Infections and infestations
Viral infection
|
0.00%
0/376
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.27%
1/375 • Number of events 1
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.00%
0/379
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
|
Injury, poisoning and procedural complications
Cartilage injury
|
0.27%
1/376 • Number of events 1
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.00%
0/375
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.00%
0/379
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
|
Investigations
LFT abnormal
|
0.00%
0/376
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.00%
0/375
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.26%
1/379 • Number of events 1
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
0.00%
0/376
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.00%
0/375
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.26%
1/379 • Number of events 1
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/376
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.00%
0/375
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.26%
1/379 • Number of events 1
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/376
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.27%
1/375 • Number of events 1
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
0.00%
0/379
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
Other adverse events
| Measure |
Matching Placebo
n=376 participants at risk
Placebo Tablets dosed once daily for 12 weeks
|
3.0 mg Plecanatide
n=375 participants at risk
Plecanatide 3.0 mg Tablets dosed once daily for 12 weeks
|
6.0 mg Plecanatide
n=379 participants at risk
Plecanatide 6.0 mg Tablets dosed once daily for 12 weeks
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
1.3%
5/376 • Number of events 5
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
3.2%
12/375 • Number of events 17
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
3.7%
14/379 • Number of events 16
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
|
Nervous system disorders
Headache
|
2.1%
8/376 • Number of events 8
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
2.4%
9/375 • Number of events 10
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
2.1%
8/379 • Number of events 10
The safety population consisted of 1130 patients who had received at least one dose of the study drug. A total of 1135 patients were randomized and five randomized patients did not receive study drug after being randomized in the study.
|
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