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

A National, 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 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: Placebo; Drug: Plecanatide

Detailed Description

This is a national, 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. 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): 1410
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Synergy Research Site
    • Huntsville, Alabama, United States, 35801
      • Synergy Research Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Synergy Research Site
    • Goodyear, Arizona, United States, 85395
      • Synergy Research Site
    • Tucson, Arizona, United States, 85704
      • Synergy Research Site
    • Tucson, Arizona, United States, 85710
      • Synergy Research Site
    • Tucson, Arizona, United States, 85712
      • Synergy Research Site
    • Tucson, Arizona, United States, 85715
      • Synergy Research Site
    • Tucson, Arizona, United States, 85745
      • Synergy Research Site
  • California
    • Anaheim, California, United States, 92801
      • Synergy Research Site
    • Artesia, California, United States, 90701
      • Synergy Research Site
    • Carmichael, California, United States, 95608
      • Synergy Research Site
    • Corona, California, United States, 92879
      • Synergy Research Site
    • Encino, California, United States, 91436
      • Synergy Research Site
    • Garden Grove, California, United States, 92843
      • Synergy Research Site
    • Garden Grove, California, United States, 92844
      • Synergy Research Site
    • Glendale, California, United States, 91204
      • Synergy Research Site
    • La Mirada, California, United States, 90638
      • Synergy Research Site
    • Laguna Hills, California, United States, 92653
      • Synergy Research Site
    • Los Angeles, California, United States, 90017
      • Synergy Research Site
    • Los Angeles, California, United States, 90036
      • Synergy Research Site
    • Newport Beach, California, United States, 92663
      • Synergy Research Site
    • Oceanside, California, United States, 92056
      • Synergy Research Site
    • Orange, California, United States, 92868
      • Synergy Research Site
    • Sacramento, California, United States, 95821
      • Synergy Research Site
    • Sacramento, California, United States, 95831
      • Synergy Research Site
    • San Bernardino, California, United States, 92408
      • Synergy Research Site
    • San Diego, California, United States, 92103
      • Synergy Research Site
    • Upland, California, United States, 91786
      • Synergy Research Site
    • Ventura, California, United States, 93003
      • Synergy Research Site
  • Colorado
    • Denver, Colorado, United States, 80209
      • Synergy Research Site
    • Littleton, Colorado, United States, 80128
      • Synergy Research Site
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Synergy Research Site
  • Florida
    • Aventura, Florida, United States, 33180
      • Synergy Research Site
    • Boynton Beach, Florida, United States, 33472
      • Synergy Research Site
    • Bradenton, Florida, United States, 34208
      • Synergy Research Site
    • Brandon, Florida, United States, 33511
      • Synergy Research Site
    • Brooksville, Florida, United States, 34601
      • Synergy Research Site
    • Clearwater, Florida, United States, 33756
      • Synergy Research Site
    • DeLand, Florida, United States, 32720
      • Synergy Research Site
    • Fort Lauderdale, Florida, United States, 33312
      • Synergy Research Site
    • Gainesville, Florida, United States, 32607
      • Synergy Research Site
    • Hialeah, Florida, United States, 33012
      • Synergy Research Site
    • Hialeah, Florida, United States, 33013
      • Synergy Research Site
    • Hialeah, Florida, United States, 33016
      • Synergy Research Site
    • Hialeah, Florida, United States, 33106
      • Synergy Research Site
    • Hollywood, Florida, United States, 33024
      • Synergy Research Site
    • Homestead, Florida, United States, 33030
      • Synergy Research Site
    • Jacksonville, Florida, United States, 32256
      • Synergy Research Site
    • Jacksonville, Florida, United States, 32277
      • Synergy Research Site
    • Miami, Florida, United States, 33014
      • Synergy Research Site
    • Miami, Florida, United States, 33015
      • Synergy Research Site
    • Miami, Florida, United States, 33032
      • Synergy Research Site
    • Miami, Florida, United States, 33122
      • Synergy Research Site
    • Miami, Florida, United States, 33125
      • Synergy Research Site
    • Miami, Florida, United States, 33126
      • Synergy Research Site
    • Miami, Florida, United States, 33142
      • Synergy Research Site
    • Miami, Florida, United States, 33144
      • Synergy Research Site
    • Miami, Florida, United States, 33155
      • Synergy Research Site
    • Miami, Florida, United States, 33157
      • Synergy Research Site
    • Miami, Florida, United States, 33165
      • Synergy Research Site
    • Miami, Florida, United States, 33173
      • Synergy Research Site
    • Miami, Florida, United States, 33175
      • Synergy Research Site
    • Miami, Florida, United States, 33176
      • Synergy Research Site
    • Miami, Florida, United States, 33185
      • Synergy Research Site
    • Miami Lakes, Florida, United States, 33016
      • Synergy Research Site
    • Miami Springs, Florida, United States, 33166
      • Synergy Research Site
    • New Port Richey, Florida, United States, 34653
      • Synergy Research Site
    • North Miami Beach, Florida, United States, 33162
      • Synergy Research Site
    • Orlando, Florida, United States, 32806
      • Synergy Research Site
    • Orlando, Florida, United States, 32807
      • Synergy Research Site
    • Ormond Beach, Florida, United States, 32174
      • Synergy Research Site
    • Pembroke Pines, Florida, United States, 33026
      • Synergy Research Site
    • Pembroke Pines, Florida, United States, 33028
      • Synergy Research Site
    • Plant City, Florida, United States, 33563
      • Synergy Research Site
    • Plantation, Florida, United States, 33324
      • Synergy Research Site
    • Saint Cloud, Florida, United States, 34769
      • Synergy Research Site
    • Saint Petersburg, Florida, United States, 33709
      • Synergy Research Site
    • Sarasota, Florida, United States, 34242
      • Synergy Research Site
    • Seminole, Florida, United States, 33777
      • Synergy Research Site
    • Tamarac, Florida, United States, 33319
      • Synergy Research Site
    • Tampa, Florida, United States, 33607
      • Synergy Research Site
    • Tampa, Florida, United States, 33614
      • Synergy Research Site
    • West Palm Beach, Florida, United States, 33409
      • Synergy Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Synergy Research Site
    • Savannah, Georgia, United States, 31406
      • Synergy Research Site
    • Snellville, Georgia, United States, 30078
      • Synergy Research Site
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Synergy Research Site
    • Boise, Idaho, United States, 83709
      • Synergy Research Site
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Synergy Research Site
    • Oak Lawn, Illinois, United States, 60453
      • Synergy Research Site
    • Schaumburg, Illinois, United States, 60194
      • Synergy Research Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Synergy Research Site
  • Kentucky
    • Madisonville, Kentucky, United States, 42431
      • Synergy Research Site
    • Owensboro, Kentucky, United States, 42303
      • Synergy Research Site
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Synergy Research Site
    • Shreveport, Louisiana, United States, 71105
      • Synergy Research Site
  • Maryland
    • Columbia, Maryland, United States, 21045
      • Synergy Research Site
  • Massachusetts
    • Watertown, Massachusetts, United States, 02472
      • Synergy Research Site
  • Michigan
    • Buckley, Michigan, United States, 49620
      • Synergy Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Synergy Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Synergy Research Site
  • Nevada
    • Las Vegas, Nevada, United States, 89103
      • Synergy Research Site
    • Las Vegas, Nevada, United States, 89106
      • Synergy Research Site
    • Stateline, Nevada, United States, 89449
      • Synergy Research Site
  • New Hampshire
    • Newington, New Hampshire, United States, 03801
      • Synergy Research Site
  • New Jersey
    • Blackwood, New Jersey, United States, 08012
      • Synergy Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Synergy Research Site
    • Albuquerque, New Mexico, United States, 87109
      • Synergy Research Site
  • New York
    • Elmsford, New York, United States, 10523
      • Synergy Research Site
    • New Hyde Park, New York, United States, 11040
      • Synergy Research Site
    • New York, New York, United States, 10016
      • Synergy Research Site
    • New York, New York, United States, 10018
      • Synergy Research Site
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Synergy Research Site
    • Concord, North Carolina, United States, 28025
      • Synergy Research Site
    • Hickory, North Carolina, United States, 28601
      • Synergy Research Site
    • Hickory, North Carolina, United States, 28602
      • Synergy Research Site
    • High Point, North Carolina, United States, 27262
      • Synergy Research Site
    • Raleigh, North Carolina, United States, 27609
      • Synergy Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45224
      • Synergy Research Site
    • Cleveland, Ohio, United States, 44122
      • Synergy Research Site
    • Columbus, Ohio, United States, 43214
      • Synergy Research Site
    • Kettering, Ohio, United States, 45429
      • Synergy Research Site
    • Middleburg Heights, Ohio, United States, 44130
      • Synergy Research Site
    • Sylvania, Ohio, United States, 43560
      • Synergy Research Site
    • Wadsworth, Ohio, United States, 44203
      • Synergy Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Synergy Research Site
    • Oklahoma City, Oklahoma, United States, 73104
      • Synergy Research Site
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • Synergy Research Site
    • Levittown, Pennsylvania, United States, 19056
      • Synergy Research Site
    • Pittsburgh, Pennsylvania, United States, 15206
      • Synergy Research Site
    • Upper Saint Clair, Pennsylvania, United States, 15241
      • Synergy Research Site
  • South Carolina
    • Greer, South Carolina, United States, 29651
      • Synergy Research Site
    • Moncks Corner, South Carolina, United States, 29461
      • Synergy Research Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • Synergy Research Site
    • Franklin, Tennessee, United States, 37064
      • Synergy Research Site
    • Jefferson City, Tennessee, United States, 37760
      • Synergy Research Site
    • Kingsport, Tennessee, United States, 37660
      • Synergy Research Site
    • Knoxville, Tennessee, United States, 37919
      • Synergy Research Site
    • Knoxville, Tennessee, United States, 37938
      • Synergy Research Site
    • Memphis, Tennessee, United States, 38119
      • Synergy Research Site
    • Nashville, Tennessee, United States, 37211
      • Synergy Research Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Synergy Research Site
    • Austin, Texas, United States, 78705
      • Synergy Research Site
    • Austin, Texas, United States, 78731
      • Synergy Research Site
    • Austin, Texas, United States, 78735
      • Synergy Research Site
    • Carrollton, Texas, United States, 75007
      • Synergy Research Site
    • Carrollton, Texas, United States, 75010
      • Synergy Research Site
    • Channelview, Texas, United States, 77530
      • Synergy Research Site
    • Dallas, Texas, United States, 75224
      • Synergy Research Site
    • Dallas, Texas, United States, 75231
      • Synergy Research Site
    • Gonzales, Texas, United States, 78629
      • Synergy Research Site
    • Houston, Texas, United States, 77015
      • Synergy Research Site
    • Houston, Texas, United States, 77025
      • Synergy Research Site
    • Houston, Texas, United States, 77054
      • Synergy Research Site
    • Houston, Texas, United States, 77062
      • Synergy Research Site
    • Pharr, Texas, United States, 78577
      • Synergy Research Site
    • Plano, Texas, United States, 75024
      • Synergy Research Site
    • Plano, Texas, United States, 75075
      • Synergy Research Site
    • Plano, Texas, United States, 75093
      • Synergy Research Site
    • Plano, Texas, United States, 75903
      • Synergy Research Site
    • San Antonio, Texas, United States, 78205
      • Synergy Research Site
    • San Antonio, Texas, United States, 78215
      • Synergy Research Site
  • Utah
    • Draper, Utah, United States, 84020
      • Synergy Research Site
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Synergy Research Site
    • Sterling, Virginia, United States, 20166
      • Synergy Research Site
  • Washington
    • Richland, Washington, United States, 99352
      • 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 American Gastroenterological Association (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 Bowel Movements (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 myocardial infarction (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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plecanatide 3.0 mg; Plecanatide tablets 3.0 mg QD for 12 weeks	Drug: Plecanatide
Placebo Comparator: Placebo; Matching placebo tablets QD for 12 weeks	Drug: Placebo
Experimental: Plecanatide 6.0 mg; Plecanatide tablets 6.0 mg QD for 12 weeks	Drug: Plecanatide

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CSBMs (CSBMs/Week) Over the 12-week Treatment Period , Mean Replacement Approach	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.	Baseline and 12 weeks
Change From Baseline in SBMs (SBMs/Week) Over the 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 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.	Baseline and 12 weeks
Change From Baseline in Average Weekly SBM Stool Consistency Over the 12-week Treatment Period, Mean Replacement Approach	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.; = 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)	Baseline and 12 weeks
Change From Baseline in Average Weekly Straining Score Over the 12-week Treatment Period, Mean Replacement Approach	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.	Baseline and 12 weeks

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.
• DeMicco M, Barrow L, Hickey B, Shailubhai K, Griffin P. Randomized clinical trial: efficacy and safety of plecanatide in the treatment of chronic idiopathic constipation. Therap Adv Gastroenterol. 2017 Nov;10(11):837-851. doi: 10.1177/1756283X17734697. Epub 2017 Oct 25.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: April 22, 2014
• First Submitted That Met QC Criteria: April 22, 2014
• First Posted (Estimate): April 24, 2014

Study Record Updates

• Last Update Posted (Actual): May 28, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: May 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; Guanylyl Cyclase C Agonists; Enzyme Activators; Plecanatide
• Other Study ID Numbers: SP304203-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No