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

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)

The purpose of this study is to confirm that the investigational medication, plecanatide, is safe and effective in treating chronic idiopathic constipation.

Study Overview

• Status: Completed
• Conditions: Chronic Idiopathic Constipation
• Intervention / Treatment: Drug: Plecanatide; Drug: Placebo; Drug: Bisacodyl

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
• Enrollment (Actual): 1394
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Synergy Research Site
  • Nova Scotia
    • Bridgewater, Nova Scotia, Canada, B4V 3N2
      • Synergy Research Site
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Synergy Research Site
    • Cambridge, Ontario, Canada, N1S 2M6
      • Synergy Research Site
    • London, Ontario, Canada, N5Y 5K7
      • Synergy Research Site
    • Oshawa, Ontario, Canada, L1H 1B9
      • Synergy Research Site
    • Sudbury, Ontario, Canada, P3E 1H5
      • Synergy Research Site
    • Toronto, Ontario, Canada, M9W 4L6
      • Synergy Research Site
    • Toronto, Ontario, Canada, M3H 5S4
      • Synergy Research Site
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Synergy Research Site
    • Pointe-Claire, Quebec, Canada, H9R 4S3
      • Synergy Research Site
    • St-Romuald, Quebec, Canada, G6W 5M6
      • Synergy Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
      • Synergy Research Site
    • Dothan, Alabama, United States, 36305
      • Synergy Research Site
    • Gulf Shores, Alabama, United States, 36542
      • Synergy Research Site
    • Huntsville, Alabama, United States, 35801
      • Synergy Research Site
    • Mobile, Alabama, United States, 36695
      • Synergy Research Site
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Synergy Research Site
    • Phoenix, Arizona, United States, 85018
      • Synergy Research Site
    • Phoenix, Arizona, United States, 85023
      • Synergy Research Site
    • Tempe, Arizona, United States, 85283
      • Synergy Research Site
    • Tucson, Arizona, United States, 85712
      • Synergy Research Site
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • Synergy Research Site
    • Little Rock, Arkansas, United States, 72211
      • Synergy Research Site
    • North Little Rock, Arkansas, United States, 72117
      • Synergy Research Site
  • California
    • Anaheim, California, United States, 92801
      • Synergy Research Site
    • Anaheim, California, United States, 92804
      • Synergy Research Site
    • Carlsbad, California, United States, 92008
      • Synergy Research Site
    • Cerritos, California, United States, 90703
      • Synergy Research Site
    • Chula Vista, California, United States, 91910
      • Synergy Research Site
    • El Cajon, California, United States, 92020
      • Synergy Research Site
    • Encinitas, California, United States, 92024
      • Synergy Research Site
    • Encino, California, United States, 91436
      • Synergy Research Site
    • Fountain Valley, California, United States, 92708
      • Synergy Research Site
    • Fresno, California, United States, 93726
      • Synergy Research Site
    • Hawaiian Gardens, California, United States, 90716
      • Synergy Research Site
    • Lancaster, California, United States, 93534
      • Synergy Research Site
    • Long Beach, California, United States, 90806
      • Synergy Research Site
    • Los Angeles, California, United States, 90045
      • Synergy Research Site
    • Los Angeles, California, United States, 90015
      • Synergy Research Site
    • Los Angeles, California, United States, 90067
      • Synergy Research Site
    • Mission Hills, California, United States, 91345
      • Synergy Research Site
    • Murrieta, California, United States, 92562
      • Synergy Research Site
    • North Hollywood, California, United States, 91606
      • Synergy Research Site
    • Oceanside, California, United States, 92054
      • Synergy Research Site
    • Oxnard, California, United States, 93030
      • Synergy Research Site
    • Pasadena, California, United States, 91105
      • Synergy Research Site
    • Poway, California, United States, 92064
      • Synergy Research Site
    • Sacramento, California, United States, 95816
      • Synergy Research Site
    • San Diego, California, United States, 92103
      • Synergy Research Site
    • San Diego, California, United States, 92108
      • Synergy Research Site
    • San Diego, California, United States, 92114
      • Synergy Research Site
    • San Diego, California, United States, 92101
      • Synergy Research Site
    • Thousand Oaks, California, United States, 91360
      • Synergy Research Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Synergy Research Site
    • Colorado Springs, Colorado, United States, 80909
      • Synergy Research Site
    • Denver, Colorado, United States, 80246
      • Synergy Research Site
    • Denver, Colorado, United States, 80218
      • Synergy Research Site
    • Denver, Colorado, United States, 80220
      • Synergy Research Site
    • Littleton, Colorado, United States, 80120
      • Synergy Research Site
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Synergy Research Site
    • Danbury, Connecticut, United States, 06810
      • Synergy Research Site
    • Waterbury, Connecticut, United States, 06708
      • Synergy Research Site
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Synergy Research Site
    • Clearwater, Florida, United States, 33759
      • Synergy Research Site
    • DeLand, Florida, United States, 32720
      • Synergy Research Site
    • Fort Lauderdale, Florida, United States, 33306
      • Synergy Research Site
    • Fort Lauderdale, Florida, United States, 33308
      • Synergy Research Site
    • Hialeah, Florida, United States, 33012
      • Synergy Research Site
    • Jupiter, Florida, United States, 33458
      • Synergy Research Site
    • Lakeland, Florida, United States, 33805
      • Synergy Research Site
    • Lynn Haven, Florida, United States, 32444
      • Synergy Research Site
    • Miami, Florida, United States, 33165
      • Synergy Research Site
    • Miami, Florida, United States, 33173
      • Synergy Research Site
    • Miami, Florida, United States, 33185
      • Synergy Research Site
    • Miami, Florida, United States, 33130
      • Synergy Research Site
    • Miami, Florida, United States, 33174
      • Synergy Research Site
    • Miami, Florida, United States, 33186
      • Synergy Research Site
    • Orlando, Florida, United States, 32806
      • Synergy Research Site
    • Orlando, Florida, United States, 32803
      • Synergy Research Site
    • Port Orange, Florida, United States, 32129
      • Synergy Research Site
    • Tampa, Florida, United States, 33606
      • Synergy Research Site
    • Tampa, Florida, United States, 33604
      • Synergy Research Site
    • Tampa, Florida, United States, 33617
      • Synergy Research Site
  • Georgia
    • Athens, Georgia, United States, 30606
      • Synergy Research Site
    • Augusta, Georgia, United States, 30912
      • Synergy Research Site
    • Decatur, Georgia, United States, 30033
      • Synergy Research Site
    • Decatur, Georgia, United States, 30032
      • Synergy Research Site
    • Johns Creek, Georgia, United States, 30097
      • Synergy Research Site
    • Oakwood, Georgia, United States, 30566
      • Synergy Research Site
    • Savannah, Georgia, United States, 31406
      • Synergy Research Site
    • Smyrna, Georgia, United States, 30082
      • Synergy Research Site
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Synergy Research Site
  • Iowa
    • Clive, Iowa, United States, 50325
      • Synergy Research Site
  • Kansas
    • Augusta, Kansas, United States, 67010
      • Synergy Research Site
    • Newton, Kansas, United States, 67114
      • Synergy Research Site
    • Shawnee Mission, Kansas, United States, 66218
      • Synergy Research Site
    • Wichita, Kansas, United States, 67205
      • Synergy Research Site
    • Wichita, Kansas, United States, 67207
      • Synergy Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Synergy Research Site
    • Lexington, Kentucky, United States, 40504
      • Synergy Research Site
  • Louisiana
    • Bastrop, Louisiana, United States, 71220
      • Synergy Research Site
    • Marrero, Louisiana, United States, 70072
      • Synergy Research Site
    • Metairie, Louisiana, United States, 70006
      • Synergy Research Site
    • New Orleans, Louisiana, United States, 70115
      • Synergy Research Site
    • New Orleans, Louisiana, United States, 70119
      • Synergy Research Site
    • Shreveport, Louisiana, United States, 71103
      • Synergy Research Site
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Synergy Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Synergy Research Site
    • Brockton, Massachusetts, United States, 02302
      • Synergy Research Site
    • New Bedford, Massachusetts, United States, 02740
      • Synergy Research Site
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Synergy Research Site
    • Flint, Michigan, United States, 48504
      • Synergy Research Site
    • Rochester, Michigan, United States, 48307
      • Synergy Research Site
    • Saginaw, Michigan, United States, 48604
      • Synergy Research Site
    • Southfield, Michigan, United States, 48034
      • Synergy Research Site
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • Synergy Research Site
    • Jackson, Mississippi, United States, 39202
      • Synergy Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Synergy Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Synergy Research Site
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Synergy Research Site
    • Las Vegas, Nevada, United States, 89119
      • Synergy Research Site
    • Las Vegas, Nevada, United States, 89121
      • Synergy Research Site
    • Reno, Nevada, United States, 89511
      • Synergy Research Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Synergy Research Site
  • New Jersey
    • Lodi, New Jersey, United States, 07644
      • Synergy Research Site
    • Ocean City, New Jersey, United States, 07712
      • Synergy Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Synergy Research Site
  • New York
    • Brooklyn, New York, United States, 11206
      • Synergy Research Site
    • Great Neck, New York, United States, 11023
      • Synergy Research Site
    • North Massapequa, New York, United States, 11758
      • Synergy Research Site
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Synergy Research Site
    • Chapel Hill, North Carolina, United States, 27599
      • Synergy Research Site
    • Charlotte, North Carolina, United States, 28210
      • Synergy Research Site
    • Charlotte, North Carolina, United States, 28277
      • Synergy Research Site
    • Greensboro, North Carolina, United States, 27403
      • Synergy Research Site
    • Kinston, North Carolina, United States, 28501
      • Synergy Research Site
    • Raleigh, North Carolina, United States, 27612
      • Synergy Research Site
    • Wilmington, North Carolina, United States, 28401
      • Synergy Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Synergy Research Site
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Synergy Research Site
  • Ohio
    • Beavercreek, Ohio, United States, 45432
      • Synergy Research Site
    • Centerville, Ohio, United States, 45459
      • Synergy Research Site
    • Cincinnati, Ohio, United States, 45246
      • Synergy Research Site
    • Hilliard, Ohio, United States, 43026
      • Synergy Research Site
    • Huber Heights, Ohio, United States, 45424
      • Synergy Research Site
    • Maumee, Ohio, United States, 43537
      • Synergy Research Site
    • Mentor, Ohio, United States, 44060
      • Synergy Research Site
    • Oakwood, Ohio, United States, 45419
      • Synergy Research Site
    • Stow, Ohio, United States, 44224
      • Synergy Research Site
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Synergy Research Site
    • Oklahoma City, Oklahoma, United States, 73102
      • Synergy Research Site
  • Pennsylvania
    • Limerick, Pennsylvania, United States, 19468
      • Synergy Research Site
    • Philadelphia, Pennsylvania, United States, 19152
      • Synergy Research Site
    • Smithfield, Pennsylvania, United States, 15478
      • Synergy Research Site
    • Yardley, Pennsylvania, United States, 19067
      • Synergy Research Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Synergy Research Site
    • Charleston, South Carolina, United States, 28406
      • Synergy Research Site
    • Columbia, South Carolina, United States, 29204
      • Synergy Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Synergy Research Site
    • Jackson, Tennessee, United States, 38305
      • Synergy Research Site
    • Nashville, Tennessee, United States, 37205
      • Synergy Research Site
    • New Tazewell, Tennessee, United States, 37825
      • Synergy Research Site
  • Texas
    • Austin, Texas, United States, 78745
      • Synergy Research Site
    • Dallas, Texas, United States, 75230
      • Synergy Research Site
    • Dallas, Texas, United States, 75234
      • Synergy Research Site
    • Houston, Texas, United States, 77062
      • Synergy Research Site
    • Houston, Texas, United States, 77043
      • Synergy Research Site
    • Houston, Texas, United States, 77070
      • Synergy Research Site
    • Houston, Texas, United States, 77090
      • Synergy Research Site
    • Killeen, Texas, United States, 76543
      • Synergy Research Site
    • Plano, Texas, United States, 75093
      • Synergy Research Site
    • San Angelo, Texas, United States, 76904
      • Synergy Research Site
    • San Antonio, Texas, United States, 78209
      • Synergy Research Site
    • San Antonio, Texas, United States, 78258
      • Synergy Research Site
    • Sugar Land, Texas, United States, 77479
      • Synergy Research Site
  • Utah
    • Logan, Utah, United States, 84341
      • Synergy Research Site
    • Saint George, Utah, United States, 84790
      • Synergy Research Site
    • Salt Lake City, Utah, United States, 84124
      • Synergy Research Site
  • Virginia
    • Christiansburg, Virginia, United States, 24073
      • Synergy Research Site
    • Henrico, Virginia, United States, 23233
      • Synergy Research Site
    • Lynchburg, Virginia, United States, 24502
      • Synergy Research Site
    • Norfolk, Virginia, United States, 23507
      • Synergy Research Site
    • Norfolk, Virginia, United States, 23502
      • Synergy Research Site
    • Richmond, Virginia, United States, 23294
      • Synergy Research Site
    • Virginia Beach, Virginia, United States, 23455
      • Synergy Research Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Synergy Research Site
    • Tacoma, Washington, United States, 98405
      • Synergy Research Site
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Synergy Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo tablets QD for 12 weeks	Drug: Placebo; Matching placebo tablets QD for 12 weeks; Other Names: Trulance placebo
Active Comparator: Plecanatide 3.0 mg; Plecanatide tablets 3.0 mg QD for 12 weeks	Drug: Plecanatide; Plecanatide tablets QD for 12 weeks; Other Names: Trulance
Active Comparator: Plecanatide 6.0 mg; Plecanatide tablets 6.0 mg QD for 12 weeks	Drug: Plecanatide; Plecanatide tablets QD for 12 weeks; Other Names: Trulance
Other: Bisacodyl; Rescue medication	Drug: Bisacodyl; Rescue medication; Other Names: Dulcolax

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Durable Overall CSBM Responders , Mean Replacement Approach	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.	12-week Treatment Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CSBMs (CSBMS/Week) Over 12-week Treatment Period, Mean Replacement Approach	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.	12-Week Treatment Period
Change From Baseline in SBM (SBMs/Week) Over 12-week Treatment Period, Mean Replacement Approach	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.	12-Week Treatment Period
Change From Baseline in Stool Consistency Score Over the 12-week Treatment Period, Mean Replacement Approach	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.; = separate hard lumps like nuts (difficult to pass); = sausage shaped but lumpy; = like a sausage but with cracks on its surface; = like a sausage or snake, smooth and soft; = soft blobs with clear-cut edges (passed easily); = fluffy pieces with ragged edges, a mushy stool; = watery, no solid pieces (entirely liquid)	12-Week Treatment Period
Change From Baseline in Straining Score Over 12-Week Treatment Period, Mean Replacement Approach	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.	12-Week Treatment Period

Collaborators and Investigators

• Sponsor: Bausch Health Americas, Inc.
• Investigators: Study Director: Mary Beth Layton, Synergy Pharmaceuticals Inc.

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: November 5, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (Estimate): November 13, 2013

Study Record Updates

• Last Update Posted (Actual): December 26, 2019
• Last Update Submitted That Met QC Criteria: December 16, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Constipation; CIC; Chronic Constipation; Synergy; Plecanatide
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Cathartics; Guanylyl Cyclase C Agonists; Enzyme Activators; Laxatives; Plecanatide; Bisacodyl
• Other Study ID Numbers: SP304203-00