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

• 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: Bausch Health Americas, Inc.
• Information provided by (Responsible Party): Bausch Health Americas, Inc.

Tracking Information

• First Submitted Date: November 5, 2013
• First Posted Date: November 13, 2013
• Results First Submitted Date: December 13, 2018
• Results First Posted Date: March 21, 2019
• Last Update Posted Date: December 26, 2019
• Study Start Date: November 2013
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2019)

Number of Durable Overall CSBM Responders , Mean Replacement Approach [ Time Frame: 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, 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.

Original Primary Outcome Measures (submitted: November 5, 2013)

Proportion of patients who are overall responders [ Time Frame: 12-week Treatment Period ]

The study's primary efficacy endpoint is the proportion of patients who are overall responders for the 12-week Treatment Period. An overall responder is defined as a weekly responder for at least 9 of the 12 treatment weeks, including at least 3 of the last 4 weeks. A weekly responder is defined as a patient who has ≥ 3 CSBMs per week and an increase from baseline of ≥1 CSBM for that week. A CSBM is a bowel movement that occurs in the absence of laxative use within 24 hours and is associated with the feeling of complete evacuation.

Current Secondary Outcome Measures (submitted: February 28, 2019)

• Change From Baseline in CSBMs (CSBMS/Week) Over 12-week Treatment Period, Mean Replacement Approach [ Time Frame: 12-Week Treatment Period ]
  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.
• Change From Baseline in SBM (SBMs/Week) Over 12-week Treatment Period, Mean Replacement Approach [ Time Frame: 12-Week Treatment Period ]
  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.
• Change From Baseline in Stool Consistency Score Over the 12-week Treatment Period, Mean Replacement Approach [ Time Frame: 12-Week Treatment Period ]
  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)
• Change From Baseline in Straining Score Over 12-Week Treatment Period, Mean Replacement Approach [ Time Frame: 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 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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 12-Week Study of Plecanatide for CIC (The CIC3 Study)
• Official Title: A Randomized, 12-Week, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of Plecanatide (3.0 and 6.0 mg) in Patients With Chronic Idiopathic Constipation (The CIC3 Study)
• Brief Summary: The purpose of this study is to confirm that the investigational medication, plecanatide, is safe and effective in treating chronic idiopathic constipation.

Detailed Description

This is a randomized, 12-week, double-blind, placebo-controlled, study in approximately 1350 adult male and female patients with CIC comparing 2 doses of plecanatide to placebo. The study will be conducted at approximately 180 clinical study sites in the United States (US) and Canada. The primary objective of the study is to evaluate the efficacy and safety of 3.0 and 6.0 mg of plecanatide administered once daily (QD) for 12 weeks in a population of patients with CIC. The study population will include only patients without other causes of constipation or other chronic conditions that could interfere with study assessments. Patients may not take laxatives (with the exception of the study-provided rescue medication, bisacodyl 5mg tablets), or a number of prohibited drugs that are known to cause constipation or diarrhea, during study participation.

There are 6 scheduled study visits, including the screening and follow-up visits. The planned duration of participation in this study will be 112 days and up to 155 days, with washout and all visit windows considered.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Idiopathic Constipation

Intervention

• Drug: Plecanatide
  Plecanatide tablets QD for 12 weeks
  Other Name: Trulance
• Drug: Placebo
  Matching placebo tablets QD for 12 weeks
  Other Name: Trulance placebo
• Drug: Bisacodyl
  Rescue medication
  Other Name: Dulcolax

Study Arms

• Active Comparator: Plecanatide 3.0 mg
  Plecanatide tablets 3.0 mg QD for 12 weeks
  Intervention: Drug: Plecanatide
• Active Comparator: Plecanatide 6.0 mg
  Plecanatide tablets 6.0 mg QD for 12 weeks
  Intervention: Drug: Plecanatide
• Placebo Comparator: Placebo
  Matching placebo tablets QD for 12 weeks
  Intervention: Drug: Placebo
• Bisacodyl
  Rescue medication
  Intervention: Drug: Bisacodyl

Publications *

• Moshiree B, Schoenfeld P, Franklin H, Rezaie A. The Effect of Acid Suppression Therapy on the Safety and Efficacy of Plecanatide: Analysis of Randomized Phase III Trials. Clin Ther. 2022 Jan;44(1):98-110.e1. doi: 10.1016/j.clinthera.2021.11.009. Epub 2022 Jan 25.
• Menees SB, Franklin H, Chey WD. Evaluation of Plecanatide for the Treatment of Chronic Idiopathic Constipation and Irritable Bowel Syndrome With Constipation in Patients 65 Years or Older. Clin Ther. 2020 Jul;42(7):1406-1414.e4. doi: 10.1016/j.clinthera.2020.05.012. Epub 2020 Jul 10.
• Miner PB Jr, Koltun WD, Wiener GJ, De La Portilla M, Prieto B, Shailubhai K, Layton MB, Barrow L, Magnus L, Griffin PH. A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation. Am J Gastroenterol. 2017 Apr;112(4):613-621. doi: 10.1038/ajg.2016.611. Epub 2017 Feb 7.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 26, 2016): 1394
• Original Estimated Enrollment (submitted: November 5, 2013): 1350
• Actual Study Completion Date: June 2015
• Actual Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Male or female aged 18-80, inclusive
• Meets modified Rome III criteria for functional chronic idiopathic constipation for at least 3 months with symptom onset for at least 6 months
• Completed a colonoscopy in accordance with AGA colon cancer screening guidelines (5 years), with no clinically significant findings
• Willing to maintain a stable diet during the study

Exclusion Criteria:

• Loose stool (mushy) or watery (Bristol score 6 or 7) stool in the absence of any laxative or prohibited medicine for > 25% of BMs during the 3 months prior to screening visit OR during the 14 day pre-treatment assessment
• Active peptic ulcer disease, diabetes or hypertension not adequately treated or not stable
• History of cathartic colon, laxative, enema abuse, or ischemic colitis
• Fecal impaction within 3 months of screening
• Patient has had /has any: diseases or conditions associated with constipation (GI or CNS), structural abnormality of the GI tract or gastric bypass surgery, pelvic floor dysfunction, pseudo-obstruction, active infectious gastritis, diverticulitis, anal fissures or any disease or condition that can affect GI motility or defecation or can be associated with abdominal pain
• Unexplained and clinically significant "alarm symptoms" including lower GI bleeding, iron-deficiency anemia, weight loss or systemic signs of infection or colitis
• Major surgery, stroke or MI within 60 days of screening
• Participated in a previous plecanatide clinical trial

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT01982240
• Other Study ID Numbers: SP304203-00
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bausch Health Americas, Inc.
• Original Responsible Party: Synergy Pharmaceuticals Inc.
• Current Study Sponsor: Bausch Health Americas, Inc.
• Original Study Sponsor: Synergy Pharmaceuticals Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Mary Beth Layton; Synergy Pharmaceuticals Inc.

• PRS Account: Bausch Health Americas, Inc.
• Verification Date: December 2019