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

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ClinicalTrials.gov Identifier: NCT02122471
Recruitment Status : Completed
First Posted : April 24, 2014
Results First Posted : March 14, 2019
Last Update Posted : May 28, 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
Enrollment 1410
Recruitment Details  
Pre-assignment Details The data are correct and approved in the NDA. 1410 randomized subj.including 95 (index and non-index) duplicate subj. The index subj (22) were duplicate appeared the first time in the study and the same subject appeared in other studies or sites were non-index duplicate (73) who were excluded in the ITT population (1337).
Arm/Group Title Placebo Plecanatide 3 mg Plecanatide 6 mg
Hide Arm/Group Description Matching placebo tablets QD for 12 weeks Plecanatide tablets 3 mg QD for 12 weeks Plecanatide tablets 6 mg QD for 12 weeks
Period Title: Overall Study
Started 445 443 449
Completed 406 392 405
Not Completed 39 51 44
Arm/Group Title Placebo Plecanatide 3 mg Plecanatide 6 mg Total
Hide Arm/Group Description Matching placebo tablets QD for 12 weeks Plecanatide tablets 3 mg QD for 12 weeks Plecanatide tablets 6 mg QD for 12 weeks Total of all reporting groups
Overall Number of Baseline Participants 445 443 449 1337
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 445 participants 443 participants 449 participants 1337 participants
44.6  (14.59) 45.5  (14.38) 45.3  (14.47) 45.1  (14.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 445 participants 443 participants 449 participants 1337 participants
Female
350
  78.7%
345
  77.9%
353
  78.6%
1048
  78.4%
Male
95
  21.3%
98
  22.1%
96
  21.4%
289
  21.6%
1.Primary Outcome
Title Number of Durable Overall CSBM Responders, Mean Replacement Approach
Hide Description The primary efficacy endpoint was measured by the number of durable overall CSBM responders over the 12-week Treatment Period. A durable overall CSBM responder was defined as a weekly CSBM responder for at least 9 of the 12 treatment weeks, including 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 modified ITT population (1310 subjects) for primary outcome was ITT population minus 27 subjects eliminated from two OAI sites. The ITT population (1337) as described in the Participate Flow consisted of the randomized subjects (1410) excluding 73 non-index subjects. "Index" subjects were duplicate subjects appeared once in the ITT population.
Arm/Group Title Placebo Plecanatide 3 mg Plecanatide 6 mg
Hide Arm/Group Description:
Matching placebo tablets QD for 12 weeks
Plecanatide tablets 3 mg QD for 12 weeks
Plecanatide tablets 6 mg QD for 12 weeks
Overall Number of Participants Analyzed 440 430 440
Measure Type: Count of Participants
Unit of Measure: Participants
57
  13.0%
88
  20.5%
88
  20.0%
2.Secondary Outcome
Title Change From Baseline in CSBMs (CSBMs/Week) Over the 12-week Treatment Period , Mean Replacement Approach
Hide Description The change from baseline in the number of Complete Spontaneous Bowel Movements (CSBMs) over the 12-week Treatment Period was analyzed. Baseline was the mean number of CSBMs recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. 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 Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 1288 patients included in ITT-E population for secondary outcome which consisted of the randomized subjects (1410) excluding 95 duplicate subjects as described in the Participate Flow and 27 subjects eliminated from two OAI sites.
Arm/Group Title Placebo Plecanatide 3 mg Plecanatide 6 mg
Hide Arm/Group Description:
Matching placebo tablets QD for 12 weeks
Plecanatide tablets 3 mg QD for 12 weeks
Plecanatide tablets 6 mg QD for 12 week
Overall Number of Participants Analyzed 432 422 434
Least Squares Mean (Standard Error)
Unit of Measure: CSBMs per week
Baseline 1.41  (0.138) 2.34  (0.139) 2.19  (0.138)
12 weeks 1.69  (0.159) 2.66  (0.162) 2.50  (0.159)
3.Secondary Outcome
Title Change From Baseline in SBMs (SBMs/Week) Over the 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 analyzed. 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.
Time Frame Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 1288 patients included in ITT-E population for secondary outcome which consisted of the randomized subjects (1410) excluding 95 duplicate subjects as described in the Participate Flow and 27 subjects eliminated from two OAI sites.
Arm/Group Title Placebo Plecanatide 3 mg Plecanatide 6 mg
Hide Arm/Group Description:
Matching placebo tablets QD for 12 weeks
Plecanatide tablets 3 mg QD for 12 weeks
Plecanatide tablets 6 mg QD for 12 weeks
Overall Number of Participants Analyzed 432 422 434
Mean (Standard Deviation)
Unit of Measure: SBMs per week
Baseline 1.55  (1.591) 1.79  (2.084) 1.63  (1.673)
12 weeks 1.81  (2.879) 3.25  (3.938) 3.10  (4.164)
4.Secondary Outcome
Title Change From Baseline in Average Weekly SBM Stool Consistency Over the 12-week Treatment Period, Mean Replacement Approach
Hide Description

The change from baseline in the stool consistency score (i.e. BSFS) over the 12-week Treatment Period was analyzed. Baseline was the mean BSFS score recorded during the 2-week baseline diary assessment period prior to the first dose of study drug. The weekly mean BSFS score per patient was derived from the BSFS entries reported during the Treatment Period in the Daily Symptom Diary.

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 Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 1288 patients included in ITT-E population for secondary outcome which consisted of the randomized subjects (1410) excluding 95 duplicate subjects as described in the Participate Flow and 27 subjects eliminated from two OAI sites.
Arm/Group Title Placebo Plecanatide 3 mg Plecanatide 6 mg
Hide Arm/Group Description:
Matching placebo tablets QD for 12 weeks
Plecanatide tablets 3 mg QD for 12 weeks
Plecanatide tablets 6 mg QD for 12 week
Overall Number of Participants Analyzed 432 422 434
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 2.35  (1.090) 2.16  (1.036) 2.27  (1.113)
12 weeks 1.02  (1.346) 1.71  (1.475) 1.59  (1.497)
5.Secondary Outcome
Title Change From Baseline in Average Weekly Straining Score Over the 12-week Treatment Period, Mean Replacement Approach
Hide Description The change from baseline in the straining score over the 12-week Treatment Period was analyzed. 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 Baseline and 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
A total of 1288 patients included in ITT-E population for secondary outcome which consisted of the randomized subjects (1410) excluding 95 duplicate subjects as described in the Participate Flow and 27 subjects eliminated from two OAI sites.
Arm/Group Title Placebo Plecanatide 3 mg Plecanatide 6 mg
Hide Arm/Group Description:
Matching placebo tablets QD for 12 weeks
Plecanatide tablets 3 mg QD for 12 weeks
Plecanatide tablets 6 mg QD for 12 weeks
Overall Number of Participants Analyzed 432 422 434
Mean (Standard Deviation)
Unit of Measure: score on a scale
Baseline 2.42  (0.855) 2.46  (0.859) 2.47  (0.888)
12 weeks -0.79  (1.132) -1.09  (1.092) -1.04  (1.084)
Time Frame [Not Specified]
Adverse Event Reporting Description The data are correct and approved in the NDA. The ITT-S population (1402) was more than the ITT population (1337) in the Participant Flow because all duplicate subjects (index and non-index) who received at lease one dose of study drug were included in the ITT-S population. A total of 1410 randomized subjects, of which eight subjects were not treated with the study drug after being enrolled and resulted in 1402 subjects.
 
Arm/Group Title Placebo Plecanatide 3 mg Plecanatide 6 mg
Hide Arm/Group Description Matching placebo tablets QD for 12 weeks Plecanatide tablets 3 mg QD for 12 weeks Plecanatide tablets 6 mg QD for 12 weeks
All-Cause Mortality
Placebo Plecanatide 3 mg Plecanatide 6 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Placebo Plecanatide 3 mg Plecanatide 6 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/466 (1.72%)      8/467 (1.71%)      4/469 (0.85%)    
Cardiac disorders       
Cardiac failure congestive † 1  0/466 (0.00%)  0 1/467 (0.21%)  1 0/469 (0.00%)  0
Ear and labyrinth disorders       
Vertigo positional † 1  0/466 (0.00%)  0 1/467 (0.21%)  1 0/469 (0.00%)  0
General disorders       
Non-cardiac chest pain † 1  1/466 (0.21%)  1 0/467 (0.00%)  0 0/469 (0.00%)  0
Hepatobiliary disorders       
Cholecystitis † 1  0/466 (0.00%)  0 1/467 (0.21%)  1 0/469 (0.00%)  0
Injury, poisoning and procedural complications       
Femoral neck fracture † 1  1/466 (0.21%)  1 0/467 (0.00%)  0 0/469 (0.00%)  0
Investigations       
Alanine aminotransferase increased † 1  1/466 (0.21%)  1 0/467 (0.00%)  0 0/469 (0.00%)  0
Aspartate aminotransferase increased † 1  0/466 (0.00%)  0 1/467 (0.21%)  1 0/469 (0.00%)  0
Liver function test abnormal † 1  0/466 (0.00%)  0 1/467 (0.21%)  1 1/469 (0.21%)  1
Musculoskeletal and connective tissue disorders       
Intervertebral disc protrusion † 1  1/466 (0.21%)  1 0/467 (0.00%)  0 0/469 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Renal cancer † 1  0/466 (0.00%)  0 1/467 (0.21%)  1 0/469 (0.00%)  0
Nervous system disorders       
Convulsion † 1  0/466 (0.00%)  0 0/467 (0.00%)  0 1/469 (0.21%)  1
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous † 1  1/466 (0.21%)  1 0/467 (0.00%)  0 0/469 (0.00%)  0
Pregnancy † 1  1/466 (0.21%)  2 1/467 (0.21%)  1 1/469 (0.21%)  1
Renal and urinary disorders       
Nephrolithiasis † 1  1/466 (0.21%)  1 0/467 (0.00%)  0 0/469 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease † 1  0/466 (0.00%)  0 1/467 (0.21%)  1 1/469 (0.21%)  1
Vascular disorders       
Arterial occlusive disease † 1  1/466 (0.21%)  1 0/467 (0.00%)  0 0/469 (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 mg Plecanatide 6 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/466 (3.22%)      25/467 (5.35%)      31/469 (6.61%)    
Gastrointestinal disorders       
Diarrhoea † 1  6/466 (1.29%)  6 15/467 (3.21%)  15 21/469 (4.48%)  25
Nervous system disorders       
Headache † 1  9/466 (1.93%)  10 10/467 (2.14%)  10 10/469 (2.13%)  10
†
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: NCT02122471    
Other Study ID Numbers: SP304203-03
First Submitted: April 22, 2014
First Posted: April 24, 2014
Results First Submitted: November 28, 2018
Results First Posted: March 14, 2019
Last Update Posted: May 28, 2019