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12-Week Study of Plecanatide for CIC (The CIC3 Study)

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ClinicalTrials.gov Identifier: NCT01982240
Recruitment Status : Completed
First Posted : November 13, 2013
Results First Posted : March 21, 2019
Last Update Posted : December 26, 2019
Sponsor:
Information provided by (Responsible Party):
Bausch Health Americas, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Idiopathic Constipation
Interventions Drug: Plecanatide
Drug: Placebo
Drug: Bisacodyl
Enrollment 1394
Recruitment Details  
Pre-assignment Details The data are correct and approved in the NDA. 1394 randomized subj.including 69 (index and non-index) duplicate subj. The index subj (21) were duplicate appeared the first time in the study and the same subject appeared in other studies or sites were non-index duplicate (48) who were excluded in the ITT population (1346).
Arm/Group Title Placebo Plecanatide 3.0 mg Plecanatide 6 mg
Hide Arm/Group Description

Matching placebo tablets QD for 12 weeks

Placebo: Matching placebo tablets QD for 12 weeks

Plecanatide tablets 3.0 mg QD for 12 weeks

Plecanatide: Plecanatide tablets QD for 12 weeks

 Plecanatide tablets 6.0 mg QD for 12 weeks
Period Title: Overall Study
Started 452 453 441
Completed 385 384 371
Not Completed 67 69 70
Arm/Group Title Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg Total
Hide Arm/Group Description Matching placebo tablets QD for 12 weeks Plecanatide tablets 3.0 mg QD for 12 weeks Plecanatide tablets 6.0 mg QD for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 452 453 441 1346
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 452 participants 453 participants 441 participants 1346 participants
46.4
(18 to 78)
45.0
(18 to 79)
45.1
(18 to 79)
45.5
(18 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 452 participants 453 participants 441 participants 1346 participants
Female
357
  79.0%
368
  81.2%
362
  82.1%
1087
  80.8%
Male
95
  21.0%
85
  18.8%
79
  17.9%
259
  19.2%
1.Primary Outcome
Title Number of Durable Overall CSBM Responders , Mean Replacement Approach
Hide Description A durable overall CSBM responder was defined as a weekly CSBM responder for at least 9 of the 12 treatment weeks, included at least 3 of the last 4 weeks. A CSBM weekly responder was defined as a patient who has ≥ 3 Complete Spontaneous Bowel Movements (CSBMs) per week and an increase from baseline of ≥1 CSBM for that week. A CSBM was a bowel movement that occurred in the absence of laxative use within 24 hours and was associated with the feeling of complete evacuation.
Time Frame 12-week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Intent-to-treat) population was used for analysis.
Arm/Group Title Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg
Hide Arm/Group Description:

Matching placebo tablets QD for 12 weeks

Placebo: Matching placebo tablets QD for 12 weeks

Plecanatide tablets 3.0 mg QD for 12 weeks

Plecanatide: Plecanatide tablets QD for 12 weeks
Plecanatide tablets 6.0 mg QD for 12 weeks
Overall Number of Participants Analyzed 452 453 441
Measure Type: Count of Participants
Unit of Measure: Participants
46
  10.2%
95
  21.0%
86
  19.5%
2.Secondary Outcome
Title Change From Baseline in CSBMs (CSBMS/Week) Over 12-week Treatment Period, Mean Replacement Approach
Hide Description A Complete Spontaneous Bowel Movement (CSBM) was a Bowel Movement (BM) that occurred in the absence of laxative use within 24 hours of the BM and the patient reported a feeling of complete evacuation. A weekly responder had 3 or more CSBMs and an increase of at least one CSBM from baseline in the same week.
Time Frame 12-Week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Intent-to-treat) population was used for analysis.
Arm/Group Title Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg
Hide Arm/Group Description:
Matching placebo tablets QD for 12 weeks
Plecanatide tablets 3.0 mg QD for 12 weeks
Plecanatide tablets 6.0 mg QD for 12 weeks
Overall Number of Participants Analyzed 452 453 441
Mean (Standard Deviation)
Unit of Measure: CSBMs per week
Baseline 0.39  (0.570) 0.32  (0.514) 0.32  (0.509)
Week 12 change from baseline 1.45  (2.310) 2.68  (3.891) 2.39  (3.296)
3.Secondary Outcome
Title Change From Baseline in SBM (SBMs/Week) Over 12-week Treatment Period, Mean Replacement Approach
Hide Description The change from baseline in the number of Spontaneous Bowel Movement (SBM) over the 12-week Treatment Period was assessed. Baseline was the mean number of SBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly SBM totals were derived from the daily diary entries reported during the Treatment Period in the BM and Symptom Diary.
Time Frame 12-Week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Intent-to-treat) population was used for analysis.
Arm/Group Title Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg
Hide Arm/Group Description:

Matching placebo tablets QD for 12 weeks

Placebo: Matching placebo tablets QD for 12 weeks

Plecanatide tablets 3.0 mg QD for 12 weeks

Plecanatide: Plecanatide tablets QD for 12 weeks
Plecanatide tablets 6.0 mg QD for 12 weeks
Overall Number of Participants Analyzed 452 453 441
Mean (Standard Deviation)
Unit of Measure: SBMs per week
Baseline 2.18  (2.032) 1.97  (1.772) 1.82  (1.824)
Week 12 change from baseline 1.37  (2.881) 3.30  (4.628) 3.24  (4.518)
4.Secondary Outcome
Title Change From Baseline in Stool Consistency Score Over the 12-week Treatment Period, Mean Replacement Approach
Hide Description

The stool consistency of each bowel movement (BM) was assessed by patients using the 7-point Bristol Stool Form Scale [BSFS] from 1 to 7.

  1. = separate hard lumps like nuts (difficult 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)
Time Frame 12-Week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Intent-to-treat) population was used for analysis.
Arm/Group Title Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg
Hide Arm/Group Description:

Matching placebo tablets QD for 12 weeks

Placebo: Matching placebo tablets QD for 12 weeks

Plecanatide tablets 3.0 mg QD for 12 weeks

Plecanatide: Plecanatide tablets QD for 12 weeks
Plecanatide tablets 6.0 mg QD for 12 weeks
Overall Number of Participants Analyzed 452 453 441
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 2.56  (1.114) 2.52  (1.046) 2.59  (1.171)
Week 12 change from baseline 0.83  (1.246) 1.56  (1.504) 1.47  (1.584)
5.Secondary Outcome
Title Change From Baseline in Straining Score Over 12-Week Treatment Period, Mean Replacement Approach
Hide Description 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 weekly average straining score was derived from the straining scores reported during the Treatment Period in the Daily Symptom Diary. The severity of straining during bowel movements was assessed on a 5-point Likert scale where 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.
Time Frame 12-Week Treatment Period
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Intent-to-treat) population was used for analysis.
Arm/Group Title Plecanatide 3.0 mg Placebo Plecanatide 6.0 mg
Hide Arm/Group Description:

Plecanatide tablets 3.0 mg QD for 12 weeks

Plecanatide: Plecanatide tablets QD for 12 weeks

Matching placebo tablets QD for 12 weeks

Placebo: Matching placebo tablets QD for 12 weeks
Plecanatide tablets 6.0 mg QD for 12 weeks
Overall Number of Participants Analyzed 453 452 441
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 2.31  (0.835) 2.30  (0.842) 2.28  (0.894)
Week 12 change from baseline -0.70  (0.967) -0.95  (1.027) -1.00  (1.155)
Time Frame [Not Specified]
Adverse Event Reporting Description The Intent-to-treat Safety (ITT-S) population (1389) was the enrolled population (1394) who received at least one dose of study drug.
 
Arm/Group Title Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg
Hide Arm/Group Description Matching placebo tablets QD for 12 weeks Plecanatide tablets 3.0 mg QD for 12 weeks Plecanatide tablets 3.0 mg QD for 12 weeks
All-Cause Mortality
Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/458 (0.87%)      6/474 (1.27%)      5/457 (1.09%)    
Gastrointestinal disorders       
Intestinal obstruction † 1  0/458 (0.00%)  0 1/474 (0.21%)  1 1/457 (0.22%)  1
Hepatobiliary disorders       
Cholelithiasis † 1  0/458 (0.00%)  0 1/474 (0.21%)  1 0/457 (0.00%)  0
Infections and infestations       
Diverticulitis † 1  1/458 (0.22%)  1 0/474 (0.00%)  0 0/457 (0.00%)  0
Mastitis † 1  1/458 (0.22%)  1 0/474 (0.00%)  0 0/457 (0.00%)  0
Pneumonia † 1  1/458 (0.22%)  1 0/474 (0.00%)  0 0/457 (0.00%)  0
Gastroenteritis † 1  0/458 (0.00%)  0 0/474 (0.00%)  0 1/457 (0.22%)  1
Staphylococcal infection † 1  0/458 (0.00%)  0 0/474 (0.00%)  0 1/457 (0.22%)  1
Injury, poisoning and procedural complications       
Ankle fracture † 1  0/458 (0.00%)  0 0/474 (0.00%)  0 1/457 (0.22%)  1
Investigations       
Aspartate aminotransferase increased † 1  0/458 (0.00%)  0 1/474 (0.21%)  1 0/457 (0.00%)  0
Nervous system disorders       
Cerebral infarction † 1  0/458 (0.00%)  0 1/474 (0.21%)  1 0/457 (0.00%)  0
Headache † 1  0/458 (0.00%)  0 0/474 (0.00%)  0 1/457 (0.22%)  1
Pregnancy, puerperium and perinatal conditions       
Pregnancy † 1  0/458 (0.00%)  0 2/474 (0.42%)  2 0/457 (0.00%)  0
Vascular disorders       
Peripheral arterial occlusive disease † 1  1/458 (0.22%)  1 0/474 (0.00%)  0 0/457 (0.00%)  0
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Placebo Plecanatide 3.0 mg Plecanatide 6.0 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/458 (1.75%)      38/474 (8.02%)      37/457 (8.10%)    
Gastrointestinal disorders       
Diarrhoea † 1  6/458 (1.31%)  6 28/474 (5.91%)  28 26/457 (5.69%)  28
Infections and infestations       
Sinusitis † 1  2/458 (0.44%)  2 10/474 (2.11%)  11 0/457 (0.00%)  0
Nasopharyngitis † 1  0/458 (0.00%)  0 0/474 (0.00%)  0 11/457 (2.41%)  12
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Patrick H. Griffin
Organization: Synergy Pharmaceuticals Inc.
Phone: 212-297-0020
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Bausch Health Americas, Inc.
ClinicalTrials.gov Identifier: NCT01982240    
Other Study ID Numbers: SP304203-00
First Submitted: November 5, 2013
First Posted: November 13, 2013
Results First Submitted: December 13, 2018
Results First Posted: March 21, 2019
Last Update Posted: December 26, 2019