Clinical trial NCT02122471: 12-Week Study of Plecanatide for CIC (The National CIC3 Study)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Idiopathic Constipation
Keywords: CIC
Constipation
Chronic Constipation
Synergy
Plecanatide
Lead sponsor: Bausch Health Americas, Inc.
Sponsor class: INDUSTRY
First posted: 2014-04-24
Enrollment: 1410
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

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 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

Primary outcomes:
measure: Number of Durable Overall CSBM Responders, Mean Replacement Approach
timeFrame: 12-Week Treatment Period
Secondary outcomes:
measure: Change From Baseline in CSBMs (CSBMs/Week) Over the 12-week Treatment Period , Mean Replacement Approach
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in SBMs (SBMs/Week) Over the 12-week Treatment Period, Mean Replacement Approach
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Average Weekly SBM Stool Consistency Over the 12-week Treatment Period, Mean Replacement Approach
timeFrame: Baseline and 12 weeks
measure: Change From Baseline in Average Weekly Straining Score Over the 12-week Treatment Period, Mean Replacement Approach
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Synergy Research Site
state: Alabama
city: Huntsville
country: United States
facility: Synergy Research Site
state: Alabama
city: Chandler
country: United States
facility: Synergy Research Site
state: Arizona
city: Goodyear
country: United States
facility: Synergy Research Site
state: Arizona
city: Tucson
country: United States
facility: Synergy Research Site
state: Arizona
city: Tucson
country: United States
facility: Synergy Research Site
state: Arizona
city: Tucson
country: United States
facility: Synergy Research Site
state: Arizona
city: Tucson
country: United States
facility: Synergy Research Site
state: Arizona
city: Tucson
country: United States
facility: Synergy Research Site
state: Arizona
city: Anaheim
country: United States
facility: Synergy Research Site
state: California
city: Artesia
country: United States
facility: Synergy Research Site
state: California
city: Carmichael
country: United States
facility: Synergy Research Site
state: California
city: Corona
country: United States
facility: Synergy Research Site
state: California
city: Encino
country: United States
facility: Synergy Research Site
state: California
city: Garden Grove
country: United States
facility: Synergy Research Site
state: California
city: Garden Grove
country: United States
facility: Synergy Research Site
state: California
city: Glendale
country: United States
facility: Synergy Research Site
state: California
city: La Mirada
country: United States
facility: Synergy Research Site
state: California
city: Laguna Hills
country: United States
facility: Synergy Research Site
state: California
city: Los Angeles
country: United States
facility: Synergy Research Site
state: California
city: Los Angeles
country: United States
facility: Synergy Research Site
state: California
city: Newport Beach
country: United States
facility: Synergy Research Site
state: California
city: Oceanside
country: United States
facility: Synergy Research Site
state: California
city: Orange
country: United States
facility: Synergy Research Site
state: California
city: Sacramento
country: United States
facility: Synergy Research Site
state: California
city: Sacramento
country: United States
facility: Synergy Research Site
state: California
city: San Bernardino
country: United States
facility: Synergy Research Site
state: California
city: San Diego
country: United States
facility: Synergy Research Site
state: California
city: Upland
country: United States
facility: Synergy Research Site
state: California
city: Ventura
country: United States
facility: Synergy Research Site
state: California
city: Denver
country: United States
facility: Synergy Research Site
state: Colorado
city: Littleton
country: United States
facility: Synergy Research Site
state: Colorado
city: Stamford
country: United States
facility: Synergy Research Site
state: Connecticut
city: Aventura
country: United States
facility: Synergy Research Site
state: Florida
city: Boynton Beach
country: United States
facility: Synergy Research Site
state: Florida
city: Bradenton
country: United States
facility: Synergy Research Site
state: Florida
city: Brandon
country: United States
facility: Synergy Research Site
state: Florida
city: Brooksville
country: United States
facility: Synergy Research Site
state: Florida
city: Clearwater
country: United States
facility: Synergy Research Site
state: Florida
city: DeLand
country: United States
facility: Synergy Research Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Synergy Research Site
state: Florida
city: Gainesville
country: United States
facility: Synergy Research Site
state: Florida
city: Hialeah
country: United States
facility: Synergy Research Site
state: Florida
city: Hialeah
country: United States
facility: Synergy Research Site
state: Florida
city: Hialeah
country: United States
facility: Synergy Research Site
state: Florida
city: Hialeah
country: United States
facility: Synergy Research Site
state: Florida
city: Hollywood
country: United States
facility: Synergy Research Site
state: Florida
city: Homestead
country: United States
facility: Synergy Research Site
state: Florida
city: Jacksonville
country: United States
facility: Synergy Research Site
state: Florida
city: Jacksonville
country: United States
facility: Synergy Research Site
state: Florida
city: Miami Lakes
country: United States
facility: Synergy Research Site
state: Florida
city: Miami Springs
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: Miami
country: United States
facility: Synergy Research Site
state: Florida
city: New Port Richey
country: United States
facility: Synergy Research Site
state: Florida
city: North Miami Beach
country: United States
facility: Synergy Research Site
state: Florida
city: Orlando
country: United States
facility: Synergy Research Site
state: Florida
city: Orlando
country: United States
facility: Synergy Research Site
state: Florida
city: Ormond Beach
country: United States
facility: Synergy Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Synergy Research Site
state: Florida
city: Pembroke Pines
country: United States
facility: Synergy Research Site
state: Florida
city: Plant City
country: United States
facility: Synergy Research Site
state: Florida
city: Plantation
country: United States
facility: Synergy Research Site
state: Florida
city: Saint Cloud
country: United States
facility: Synergy Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Synergy Research Site
state: Florida
city: Sarasota
country: United States
facility: Synergy Research Site
state: Florida
city: Seminole
country: United States
facility: Synergy Research Site
state: Florida
city: Tamarac
country: United States
facility: Synergy Research Site
state: Florida
city: Tampa
country: United States
facility: Synergy Research Site
state: Florida
city: Tampa
country: United States
facility: Synergy Research Site
state: Florida
city: West Palm Beach
country: United States
facility: Synergy Research Site
state: Florida
city: Atlanta
country: United States
facility: Synergy Research Site
state: Georgia
city: Savannah
country: United States
facility: Synergy Research Site
state: Georgia
city: Snellville
country: United States
facility: Synergy Research Site
state: Georgia
city: Blackfoot
country: United States
facility: Synergy Research Site
state: Idaho
city: Boise
country: United States
facility: Synergy Research Site
state: Idaho
city: Chicago
country: United States
facility: Synergy Research Site
state: Illinois
city: Oak Lawn
country: United States
facility: Synergy Research Site
state: Illinois
city: Schaumburg
country: United States
facility: Synergy Research Site
state: Illinois
city: Evansville
country: United States
facility: Synergy Research Site
state: Indiana
city: Madisonville
country: United States
facility: Synergy Research Site
state: Kentucky
city: Owensboro
country: United States
facility: Synergy Research Site
state: Kentucky
city: Monroe
country: United States
facility: Synergy Research Site
state: Louisiana
city: Shreveport
country: United States
facility: Synergy Research Site
state: Louisiana
city: Columbia
country: United States
facility: Synergy Research Site
state: Maryland
city: Watertown
country: United States
facility: Synergy Research Site
state: Massachusetts
city: Buckley
country: United States
facility: Synergy Research Site
state: Michigan
city: Saint Louis
country: United States
facility: Synergy Research Site
state: Missouri
city: Omaha
country: United States
facility: Synergy Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Synergy Research Site
state: Nevada
city: Las Vegas
country: United States
facility: Synergy Research Site
state: Nevada
city: Stateline
country: United States
facility: Synergy Research Site
state: Nevada
city: Newington
country: United States
facility: Synergy Research Site
state: New Hampshire
city: Blackwood
country: United States
facility: Synergy Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Synergy Research Site
state: New Mexico
city: Albuquerque
country: United States
facility: Synergy Research Site
state: New Mexico
city: Elmsford
country: United States
facility: Synergy Research Site
state: New York
city: New Hyde Park
country: United States
facility: Synergy Research Site
state: New York
city: New York
country: United States
facility: Synergy Research Site
state: New York
city: New York
country: United States
facility: Synergy Research Site
state: New York
city: Cary
country: United States
facility: Synergy Research Site
state: North Carolina
city: Concord
country: United States
facility: Synergy Research Site
state: North Carolina
city: Hickory
country: United States
facility: Synergy Research Site
state: North Carolina
city: Hickory
country: United States
facility: Synergy Research Site
state: North Carolina
city: High Point
country: United States
facility: Synergy Research Site
state: North Carolina
city: Raleigh
country: United States
facility: Synergy Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Synergy Research Site
state: Ohio
city: Cleveland
country: United States
facility: Synergy Research Site
state: Ohio
city: Columbus
country: United States
facility: Synergy Research Site
state: Ohio
city: Kettering
country: United States
facility: Synergy Research Site
state: Ohio
city: Middleburg Heights
country: United States
facility: Synergy Research Site
state: Ohio
city: Sylvania
country: United States
facility: Synergy Research Site
state: Ohio
city: Wadsworth
country: United States
facility: Synergy Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Synergy Research Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Synergy Research Site
state: Oklahoma
city: Jenkintown
country: United States
facility: Synergy Research Site
state: Pennsylvania
city: Levittown
country: United States
facility: Synergy Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Synergy Research Site
state: Pennsylvania
city: Upper Saint Clair
country: United States
facility: Synergy Research Site
state: Pennsylvania
city: Greer
country: United States
facility: Synergy Research Site
state: South Carolina
city: Moncks Corner
country: United States
facility: Synergy Research Site
state: South Carolina
city: Bristol
country: United States
facility: Synergy Research Site
state: Tennessee
city: Franklin
country: United States
facility: Synergy Research Site
state: Tennessee
city: Jefferson City
country: United States
facility: Synergy Research Site
state: Tennessee
city: Kingsport
country: United States
facility: Synergy Research Site
state: Tennessee
city: Knoxville
country: United States
facility: Synergy Research Site
state: Tennessee
city: Knoxville
country: United States
facility: Synergy Research Site
state: Tennessee
city: Memphis
country: United States
facility: Synergy Research Site
state: Tennessee
city: Nashville
country: United States
facility: Synergy Research Site
state: Tennessee
city: Arlington
country: United States
facility: Synergy Research Site
state: Texas
city: Austin
country: United States
facility: Synergy Research Site
state: Texas
city: Austin
country: United States
facility: Synergy Research Site
state: Texas
city: Austin
country: United States
facility: Synergy Research Site
state: Texas
city: Carrollton
country: United States
facility: Synergy Research Site
state: Texas
city: Carrollton
country: United States
facility: Synergy Research Site
state: Texas
city: Channelview
country: United States
facility: Synergy Research Site
state: Texas
city: Dallas
country: United States
facility: Synergy Research Site
state: Texas
city: Dallas
country: United States
facility: Synergy Research Site
state: Texas
city: Gonzales
country: United States
facility: Synergy Research Site
state: Texas
city: Houston
country: United States
facility: Synergy Research Site
state: Texas
city: Houston
country: United States
facility: Synergy Research Site
state: Texas
city: Houston
country: United States
facility: Synergy Research Site
state: Texas
city: Houston
country: United States
facility: Synergy Research Site
state: Texas
city: Pharr
country: United States
facility: Synergy Research Site
state: Texas
city: Plano
country: United States
facility: Synergy Research Site
state: Texas
city: Plano
country: United States
facility: Synergy Research Site
state: Texas
city: Plano
country: United States
facility: Synergy Research Site
state: Texas
city: Plano
country: United States
facility: Synergy Research Site
state: Texas
city: San Antonio
country: United States
facility: Synergy Research Site
state: Texas
city: San Antonio
country: United States
facility: Synergy Research Site
state: Texas
city: Draper
country: United States
facility: Synergy Research Site
state: Utah
city: Newport News
country: United States
facility: Synergy Research Site
state: Virginia
city: Sterling
country: United States
facility: Synergy Research Site
state: Virginia
city: Richland
country: United States
facility: Synergy Research Site
state: Washington
Study officials:
affiliation: Synergy Pharmaceuticals Inc.
name: Mary Beth Layton
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.