A Phase 3, International, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Efficacy and Safety Trial of Linaclotide Administered Orally for 12 Weeks to Patients With Irritable Bowel Syndrome With Constipation (IBS-C) (D5630C00001)

This clinical trial is an international, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial comparing one dose of linaclotide to placebo. Approximately 800 patients with a diagnosis of IBS-C (modified Rome III criteria) will be randomized at up to 60 trial centers in China, Australia, and New Zealand.

The trial will consist of up to 21 days of screening, 14 to 21 days of pre-treatment, 12 weeks of double-blind treatment, and 2 weeks of follow-up. At the end of the Pre-treatment Period, patients meeting the entry criteria for this trial will be randomized to one of two double-blind treatment groups: 290 ug linaclotide, or placebo (1:1).

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Constipation (IBS-C)
• Intervention / Treatment: Drug: Placebo; Drug: Linaclotide

• Study Type: Interventional
• Enrollment (Actual): 1722
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • Research Site
  • Brisbane, Australia
    • Research Site
  • Five Dock, Australia
    • Research Site
  • Malvern, Australia
    • Research Site
  • Maroubra, Australia
    • Research Site
  • Melbourne, Australia
    • Research Site
  • Parkville, Australia
    • Research Site
• Canada
  • Ontario
    • Vaughan, Ontario, Canada
      • Research Site
• China
  • Beijing, China
    • Research Site
  • Changsha, China
    • Research Site
  • Chengdu, China
    • Research Site
  • Chongqing, China
    • Research Site
  • Guangzhou, China
    • Research Site
  • Hangzhou, China
    • Research Site
  • Harerbin, China
    • Research Site
  • Hefei, China
    • Research Site
  • Jinan, China
    • Research Site
  • Nanchang, China
    • Research Site
  • Qingdao, China
    • Research Site
  • Shanghai, China
    • Research Site
  • Shenyang, China
    • Research Site
  • Shijiazhuang, China
    • Research Site
  • Wuhan, China
    • Research Site
  • Xi An, China
    • Research Site
  • Xiamen, China
    • Research Site
• New Zealand
  • Auckland, New Zealand
    • Research Site
  • Christchurch, New Zealand
    • Research Site
  • Dunedin, New Zealand
    • Research Site
  • Tauranga, New Zealand
    • Research Site
  • Wellington, New Zealand
    • Research Site
• United States
  • Alabama
    • Huntsville, Alabama, United States
      • Research Site
  • Arkansas
    • North Little Rock, Arkansas, United States
      • Research Site
    • Phoenix, Arkansas, United States
      • Research Site
  • California
    • Artesia, California, United States
      • Research Site
    • Chula Vista, California, United States
      • Research Site
    • Encino, California, United States
      • Research Site
    • North Hollywood, California, United States
      • Research Site
    • Orange, California, United States
      • Research Site
    • Riverside, California, United States
      • Research Site
    • San Diego, California, United States
      • Research Site
  • Florida
    • Boynton Beach, Florida, United States
      • Research Site
    • Brandon, Florida, United States
      • Research Site
    • Brooksville, Florida, United States
      • Research Site
    • Doral, Florida, United States
      • Research Site
    • Gainesville, Florida, United States
      • Research Site
    • Hialeah, Florida, United States
      • Research Site
    • Kissimmee, Florida, United States
      • Research Site
    • Lauderdale Lakes, Florida, United States
      • Research Site
    • Miami, Florida, United States
      • Research Site
    • Miami Lakes, Florida, United States
      • Research Site
  • Illinois
    • Addison, Illinois, United States
      • Research Site
  • Indiana
    • Evansville, Indiana, United States
      • Research Site
  • Louisiana
    • Crowley, Louisiana, United States
      • Research Site
    • Monroe, Louisiana, United States
      • Research Site
    • Shreveport, Louisiana, United States
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • Research Site
  • Michigan
    • Chesterfield, Michigan, United States
      • Research Site
    • Wyoming, Michigan, United States
      • Research Site
  • Missouri
    • St. Louis, Missouri, United States
      • Research Site
  • Montana
    • Billings, Montana, United States
      • Research Site
  • Nevada
    • Las Vegas, Nevada, United States
      • Research Site
  • New York
    • Brooklyn, New York, United States
      • Research Site
    • Great Neck, New York, United States
      • Research Site
    • New York, New York, United States
      • Research Site
  • North Carolina
    • Raleigh, North Carolina, United States
      • Research Site
    • Salisbury, North Carolina, United States
      • Research Site
    • Winston-Salem, North Carolina, United States
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Research Site
    • Dayton, Ohio, United States
      • Research Site
    • Franklin, Ohio, United States
      • Research Site
    • Mentor, Ohio, United States
      • Research Site
  • South Carolina
    • Greer, South Carolina, United States
      • Research Site
  • Tennessee
    • Chattanooga, Tennessee, United States
      • Research Site
    • Kingsport, Tennessee, United States
      • Research Site
    • Knoxville, Tennessee, United States
      • Research Site
    • Smyrna, Tennessee, United States
      • Research Site
  • Texas
    • Houston, Texas, United States
      • Research Site
    • San Antonio, Texas, United States
      • Research Site
    • Webster, Texas, United States
      • Research Site
  • Utah
    • Ogden, Utah, United States
      • Research Site
  • Virginia
    • Lynchburg, Virginia, United States
      • Research Site
  • West Virginia
    • Morgantown, West Virginia, United States
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patient has signed an Informed Consent Form(ICF).
2. Patient Must not be pregnant or breastfeeding and agree to use birth control
3. Patient meets the colonoscopy requirements defined by the American Gastroenterological Association guidelines and no clinically-significant laboratory or physical examination findings;
4. Patient meets protocol-defined criteria for Irritable Bowel Syndrome with Constipation(IBS-C), including stool frequency, straining, stool consistency, abdominal pain, and abdominal discomfort criteria
5. Patient meets protocol-defined eDiary completion Compliance and agrees to refrain from making any new, major life-style changes that may affect IBS-C symptoms

Exclusion Criteria:

1. Recent history of mushy or watery stools
2. Various medical conditions, medical histories, or family medical histories that would not make the patient a good candidate for the study
3. Patient currently has both unexplained and clinically significant alarm symptoms or systemic signs of infection or colitis.
4. Surgery to the gastrointestinal tract
5. Usage of prohibited medications

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment arm	Drug: Linaclotide; Linaclotide 290 ug Capsules, Oral, once daily
Placebo Comparator: controlled arm	Drug: Placebo; matching Placebo Capsules, Oral, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-week Abdominal Pain/Abdominal Discomfort Weekly Responder	A 12-week Abdominal Pain/Abdominal Discomfort Responder is a patient who meets the Abdominal Pain/Abdominal Discomfort Weekly Responder criteria (i.e., an improvement of ≥30% from baseline in either the mean abdominal pain score or mean abdominal discomfort score for that week, with neither score worsening from baseline for that week) for at least 6 out of the 12 weeks of the Treatment Period. Abdominal pain at its worst (in the last 24 hours) was assessed daily by patients on an 11-point numerical rating scale (NRS) where 0 represents no abdominal pain and 10 represents very severe abdominal pain. Abdominal discomfort (in the last 24 hours) was assessed daily by patients on an 11-point NRS where 0 represents no abdominal discomfort and 10 represents very severe abdominal discomfort.	Baseline and Weeks 1-12 during the Treatment Period
12-week Irritable Bowel Syndrome (IBS) Degree of Relief Responder	A 12-week IBS Degree of Relief Responder is a patient who meets the IBS Degree of Relief Weekly Responder criteria (i.e., response to the degree of relief of IBS symptoms question for that week was "Considerably relieved" or "Completely relieved") for at least 6 out of the 12 weeks of the Treatment Period. Degree of relief of IBS symptoms (in the last 7 days) was assessed weekly by patients on a 7-point balanced ordinal scale where 1 = Completely relieved, 4 = Unchanged, and 7 = As bad as I can imagine.	Baseline and Weeks 1-12 during the Treatment Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 12-week Complete Spontaneous Bowel Movement Frequency Rate	The change from baseline in 12-week CSBM frequency (i.e., average weekly CSBM frequency over the 12 weeks of the Treatment Period). A spontaneous bowel movement (SBM) is defined as a bowel movement without laxative use in the preceding 24 hours. A CSBM is defined as an SBM that is associated with a sense of complete evacuation.	Baseline and 12-week Treatment Period
Change From Baseline in 12-week Spontaneous Bowel Movement Frequency Rate	The change from baseline in 12-week SBM frequency (i.e., average weekly SBM frequency over the 12 weeks of the Treatment Period). SBM is defined as a bowel movement without laxative use in the preceding 24 hours.	Baseline and 12-week Treatment Period
Change From Baseline in 12-week Stool Consistency	The change from baseline in 12-week stool consistency (i.e., the average of the non-missing Bristol Stool Form Scale [BSFS] score from the SBMs occurring during the 12-week Treatment Period). Consistency of each bowel movement was assessed daily by patients using the 7-point BSFS (1=Separate hard lumps like nuts [difficult to pass] to 7=Watery, no solid pieces [entirely liquid]).	Baseline and 12-week Treatment Period
Change From Baseline in 12-week Severity of Straining	The change from baseline in 12-week severity of straining (i.e., the average of the non-missing straining scores from the SBMs occurring during the 12-week Treatment Period). Severity of straining was assessed daily by patients on a 5-point ordinal scale (1=Not at all to 5=An extreme amount).	Baseline and 12-week Treatment Period
Change From Baseline in 12-week Abdominal Bloating	The change from baseline in 12-week abdominal bloating (i.e., the average of the non-missing daily abdominal bloating scores reported during the 12-week Treatment Period). Abdominal bloating (in the last 24 hours) was assessed daily by patients on an 11-point NRS where 0 represents no abdominal bloating and 10 represents very severe abdominal bloating.	Baseline and 12-week Treatment Period
Change From Baseline in 12-week Abdominal Pain	The change from baseline in 12-week abdominal pain (i.e., the average of the non-missing daily abdominal pain scores reported during the 12-week Treatment Period). Abdominal pain at its worst (in the last 24 hours) was assessed daily by patients on an 11-point NRS where 0 represents no abdominal pain and 10 represents very severe abdominal pain.	Baseline and 12-week Treatment Period
Change From Baseline in 12-week Abdominal Discomfort	The change from baseline in 12-week abdominal discomfort (i.e., the average of the non-missing daily abdominal discomfort scores reported during the 12-week Treatment Period). Abdominal discomfort (in the last 24 hours) was assessed daily by patients on an 11-point NRS where 0 represents no abdominal discomfort and 10 represents very severe abdominal discomfort.	Baseline and 12-week Treatment Period

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Ironwood Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Shutian Zhang, Beijing Friendship Hospital; Principal Investigator: Yunsheng Yang, Chinese PLA General Hospital; Principal Investigator: Zhaoshen Li, Changhai Hospital Affiliated to Second Military Mecical University of Chinese PLA; Principal Investigator: Weifen Xie, Changzheng Hospital Affiliated to Second Military Mecical University of Chinese PLA; Principal Investigator: Yaozong Yuan, Ruijin Hospital Affiliated to Medical College of Shanghai Jiaotong University; Principal Investigator: Youqing Xu, Beijing TianTan Hospital; Principal Investigator: Dongfeng Chen, The Third Affiliated Hospital of Third Military Mecical University of Chinese PLA; Principal Investigator: Minhu Chen, The First Affiliated Hospital, Zhongshan (Sun Yat-sen) University; Principal Investigator: Yanqing Li, Qilu Hospital of Shandong University; Principal Investigator: Xiaozhong Guo, General Hospital of Shenyang Military Region of Chinese PLA; Principal Investigator: Youlin Yang, First Affiliated Hospital of Harbin Medical University; Principal Investigator: Rongquan Wang, The First Affiliated Hospital of Third Military Mecical University of Chinese PLA; Principal Investigator: Xiaohua Hou, Union Hospital of Tongji Medical College of Huazhong University of Science & Technology; Principal Investigator: Liangping Li, Sichuang Provincial People's Hospital; Principal Investigator: Chengwei Tang, West China Hospital; Principal Investigator: Jianlin Ren, Zhongshan Hospital Affiliated to Xiamen University; Principal Investigator: Xizhong Shen, Shanghai Zhongshan Hospital; Principal Investigator: Yulan Liu, Peking University People's Hospital; Principal Investigator: Dongmei Qian, Beijing Tongren Hospital Affiliated to Capital Medical University; Principal Investigator: Huahong Wang, Peking University First Hospital

Publications and helpful links

General Publications

• Peng LH, Fang JY, Dai N, Shen XZ, Yang YL, Sun J, Yang YS. Efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation: Chinese sub-cohort analysis of a phase III, randomized, double-blind, placebo-controlled trial. J Dig Dis. 2022 Feb;23(2):99-110. doi: 10.1111/1751-2980.13081.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: June 12, 2013
• First Submitted That Met QC Criteria: June 17, 2013
• First Posted (Estimate): June 19, 2013

Study Record Updates

• Last Update Posted (Estimate): September 27, 2016
• Last Update Submitted That Met QC Criteria: August 4, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Constipation; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; Linaclotide
• Other Study ID Numbers: ICP-103-307