Phase III, Randomized, Double-Blind, Placebo-Controlled, Trial of Linaclotide Administered to Patients With Chronic Constipation

NCT00765882 | Completed Phase 3 Results

• 1 other identifier: LIN-MD-01
• Study Type: interventional
• Target: 633
• Locations: 2 countries
• Sites: 108

Brief Summary

The objective of this trial is to determine the efficacy and safety of linaclotide administered to patients with chronic constipation (CC). The primary efficacy parameter is the percentage of patients in each treatment group that meet the protocol definition for Complete Spontaneous Bowel Movement (CSBM) Overall Responder

Conditions

Chronic Constipation

Keywords

Constipation; Chronic Constipation; Linaclotide

Outcome Measures

Primary Outcomes (1)

• Complete Spontaneous Bowel Movement (CSBM) Overall Responder

  A 12-week CSBM overall responders was defined as a patient who for at least 9 of the 12 weeks of the treatment period had a CSBM weekly frequency rate that was 3 or greater and increased by 1 or more from baseline. A CSBM was defined as a spontaneous bowel movement (SBM) that was associated with a sense of complete evacuation. An SBM was defined as a bowel movement (BM) that occurred in the absence of laxative, enema, or suppository use on either the calendar day of the BM or the calendar day before the BM.

  Change from Baseline to Week 12

Secondary Outcomes (7)

• 12-week Complete Spontaneous Bowel Movement (CSBM) Frequency Rate

  Change from Baseline to Week 12

• 12-Week Spontaneous Bowel Movement (SBM) Frequency Rate

  Change from Baseline to Week 12

• 12-Week Stool Consistency

  Change from Baseline to Week 12

• 12-Week Severity of Straining

  Change from Baseline to Week 12

• 12-Week Abdominal Discomfort

  Change from Baseline to Week 12

Study Arms (3)

1

EXPERIMENTAL

Linaclotide 290 micrograms

Drug: Linaclotide 290 micrograms

2

EXPERIMENTAL

Linaclotide 145 micrograms

Drug: Linaclotide 145 micrograms

3

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

Linaclotide 290 micrograms DRUG

Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

1

Linaclotide 145 micrograms DRUG

Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

2

Placebo DRUG

Oral, once daily each morning at least 30 minutes before breakfast for the duration of the study

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has completed a colonoscopy according to the AGA criteria, with no clinically significant findings
• Patient has successfully completed protocol procedures (with no clinically significant findings): physical exam, 12-lead ECG, or clinical laboratory tests
• Patient meets protocol criteria for CC: reports \< 3 bowel movements per week and reports straining, lumpy or hard stools, and/or sensation of incomplete evacuation during \> 25% of BMs
• Patient demonstrates continued chronic constipation through Pretreatment Period
• Patient is compliant with IVRS

You may not qualify if:

• Patient has history of loose or watery stools
• Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS)
• Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility
• Patient has any protocol-excluded or clinically significant medical or surgical history that could confound the study assessments

Sponsors & Collaborators

• Forest Laboratories: lead
• Ironwood Pharmaceuticals, Inc.: collaborator

Study Sites (108)

Forest Investigative Site

Birmingham, Alabama, 35205, United States

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Forest Investigative Site

Birmingham, Alabama, 35215, United States

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Forest Investigative Site

Huntsville, Alabama, 35801, United States

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Forest Investigative Site

Chandler, Arizona, 85225, United States

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Forest Investigative Site

Mesa, Arizona, 85210, United States

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Forest Investigative Site

Peoria, Arizona, 85381, United States

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Forest Investigative Site

Phoenix, Arizona, 85012, United States

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Forest Investigative Site

Scottsdale, Arizona, 85251, United States

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Forest Investigative Site

Tucson, Arizona, 85741, United States

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Forest Investigative Site

Burbank, California, 91505, United States

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Forest Investigative Site

Encinitas, California, 92024, United States

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Forest Investigative Site

Foothill Ranch, California, 92610, United States

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Forest Investigative Site

Los Angeles, California, 90036, United States

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Forest Investigative Site

Orange, California, 92869, United States

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Forest Investigative Site

Westlake Village, California, 91361, United States

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Forest Investigative Site

Boulder, Colorado, 80304, United States

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Forest Investigative Site

Colorado Springs, Colorado, 80909, United States

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Forest Investigative Sites

Denver, Colorado, 80205, United States

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Forest Investigative Site

Longmont, Colorado, 80501, United States

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Forest Investigative Site

Wheat Ridge, Colorado, 80033, United States

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Forest Investigative Site

Waterbury, Connecticut, 06708, United States

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Forest Investigative Site

Boca Raton, Florida, 33486, United States

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Forest Investigative Site

Bradenton, Florida, 34203, United States

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Forest Investigative Site

Brooksville, Florida, 34601, United States

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Forest Investigative Site

Fort Myers, Florida, 33916, United States

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Forest Investigative Site

Jupiter, Florida, 33458, United States

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Forest Investigative Site

Kissimmee, Florida, 34741, United States

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Forest Investigative Site

Miami, Florida, 33143, United States

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Forest Investigative Site

Ocala, Florida, 34471, United States

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Forest Investigative Site

Orlando, Florida, 32806, United States

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Forest Investigative Site

Panama City, Florida, 32405, United States

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Forest Investigative Site

Pembroke Pines, Florida, 33024, United States

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Forest Investigative Site

St. Petersburg, Florida, 33709, United States

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Forest Investigative Site

Tampa, Florida, 33606, United States

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Forest Investigative Site

Trinity, Florida, 34655, United States

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Forest Investigative Site

Zephyrhills, Florida, 33542, United States

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Forest Investigative Site

Atlanta, Georgia, 30342, United States

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Forest Investigative Site

Marietta, Georgia, 30060, United States

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Forest Investigative Site

Marietta, Georgia, 30067, United States

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Forest Investigative Site

Stockbridge, Georgia, 30281, United States

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Forest Investigative Site

Woodstock, Georgia, 30189, United States

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Forest Investigative Site

Idaho Falls, Idaho, 83404, United States

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Forest Investigative Site

Rockford, Illinois, 61107, United States

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Forest Investigative Site

Elkhart, Indiana, 46514, United States

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Forest Investigative Site

Evansville, Indiana, 47714, United States

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Forest Investigative Site

Indianapolis, Indiana, 46237, United States

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Forest Investigative Site

Indianapolis, Indiana, 46254, United States

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Forest Investigative Site

Iowa City, Iowa, 52242, United States

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Forest Investigative Site

Arkansas City, Kansas, 67005, United States

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Forest Investigative Site

Newton, Kansas, 67114, United States

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Forest Investigative Site

Wichita, Kansas, 67205, United States

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Forest Investigative Site

Wichita, Kansas, 67207, United States

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Forest Investigative Site

Lexington, Kentucky, 40509, United States

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Forest Investigative Site

Madisonville, Kentucky, 42431, United States

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Forest Investigative Site

Chevy Chase, Maryland, 20815, United States

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Forest Investigative Site

Hagerstown, Maryland, 21742, United States

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Forest Investigative Site

Lutherville, Maryland, 21093, United States

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Forest Investigative Site

Boston, Massachusetts, 02135, United States

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Forest Investigative Site

Chaska, Minnesota, 55318, United States

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Forest Investigative Site

St Louis, Missouri, 63110, United States

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Forest Investigative Site

St Louis, Missouri, 63128, United States

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Forest Investigative Site

Vineland, New Jersey, 08360, United States

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Forest Investigative Site

Albuquerque, New Mexico, 87106, United States

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Forest Investigative Site

Brooklyn, New York, 11214, United States

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Forest Investigative Site

Great Neck, New York, 11021, United States

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Forest Investigative Site

Great Neck, New York, 11023, United States

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Forest Investigative Site

Fayetteville, North Carolina, 28304, United States

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Forest Investigative Site

Greensboro, North Carolina, 27403, United States

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Forest Investigative Site

Hickory, North Carolina, 28601, United States

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Forest Investigative Site

Raleigh, North Carolina, 27612, United States

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Forest Investigative Site

Wilmington, North Carolina, 28401, United States

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Forest Investigative Site

Winston-Salem, North Carolina, 27103, United States

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Forest Investigative Site

Bismarck, North Dakota, 58501, United States

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Forest Investigative Site

Akron, Ohio, 44302, United States

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Forest Investigative Site

Cincinnati, Ohio, 45219, United States

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Forest Investigative Site

Cleveland, Ohio, 44122, United States

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Forest Investigative Site

Oklahoma City, Oklahoma, 73104, United States

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Forest Investigative Site

Tulsa, Oklahoma, 74135, United States

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Forest Investigative Site

Bensalem, Pennsylvania, 19020, United States

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Forest Investigative Site

Pittsburgh, Pennsylvania, 15206, United States

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Forest Investigative Site

Greenville, South Carolina, 29615, United States

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Forest Investigative Site

Greer, South Carolina, 29651, United States

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Forest Investigative Site

Nashville, Tennessee, 37205, United States

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Forest Investigative Site

Austin, Texas, 78705, United States

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Forest Investigative Site

Dallas, Texas, 75234, United States

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Forest Investigative Site

Houston, Texas, 77090, United States

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Forest Investigative Site

Lake Jackson, Texas, 77566, United States

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Forest Investigative Site

San Antonio, Texas, 78209, United States

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Forest Investigative Site

San Antonio, Texas, 78229, United States

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Forest Investigative Site

Salt Lake City, Utah, 84102, United States

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Forest Investigative Site

Charlottesville, Virginia, 22911, United States

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Forest Investigative Site

Christianburg, Virginia, 24073, United States

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Forest Investigative Site

Newport News, Virginia, 23606, United States

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Forest Investigative Site

Norfolk, Virginia, 23502, United States

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Forest Investigative Site

Norfolk, Virginia, 23507, United States

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Forest Investigative Site

Richmond, Virginia, 23294, United States

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Forest Investigative Site

Bellevue, Washington, 98402, United States

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Forest Investigative Site

Lakewood, Washington, 98499, United States

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Forest Investigative Site

Wenatchee, Washington, 98801, United States

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Forest Investigative Site

Milwaukee, Wisconsin, 53209, United States

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Forest Investigative Site

Vancouver, British Columbia, V67 2K5, Canada

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Forest Investigative Site

Greater Sudbury, Ontario, P3E 1H5, Canada

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Forest Investigative Site

Hamilton, Ontario, L8N 4A6, Canada

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Forest Investigative Site

Newmarket, Ontario, L3Y 7V1, Canada

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Forest Investigative Site

Ottawa, Ontario, K2c 3R2, Canada

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Forest Investigative Site 1

Sarnia, Ontario, N7T 4X3, Canada

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Forest Investigative Site 2

Sarnia, Ontario, N7T 4X3, Canada

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Forest Investigative Site

Toronto, Ontario, MCN 2V7, Canada

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Related Publications (2)

• Chang L, Lembo AJ, Lavins BJ, Shiff SJ, Hao X, Chickering JG, Jia XD, Currie MG, Kurtz CB, Johnston JM. The impact of abdominal pain on global measures in patients with chronic idiopathic constipation, before and after treatment with linaclotide: a pooled analysis of two randomised, double-blind, placebo-controlled, phase 3 trials. Aliment Pharmacol Ther. 2014 Dec;40(11-12):1302-12. doi: 10.1111/apt.12985. Epub 2014 Oct 13.

  PMID: 25312449 DERIVED

• Lembo AJ, Schneier HA, Shiff SJ, Kurtz CB, MacDougall JE, Jia XD, Shao JZ, Lavins BJ, Currie MG, Fitch DA, Jeglinski BI, Eng P, Fox SM, Johnston JM. Two randomized trials of linaclotide for chronic constipation. N Engl J Med. 2011 Aug 11;365(6):527-36. doi: 10.1056/NEJMoa1010863.

  PMID: 21830967 DERIVED

MeSH Terms

Conditions

Constipation

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Paul F.C. Eng, PhD. Director, Clinical Development
• Organization: Forest Research Institute

Paul.Eng@frx.com

201-427-8071

Study Officials

• Paul F.C. Eng, PhD

  Forest Laboratories

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2008
• First Posted: October 3, 2008
• Study Start: September 1, 2008
• Primary Completion: July 1, 2009
• Study Completion: August 1, 2009
• Last Updated: January 30, 2013
• Results First Posted: January 30, 2013

Record last verified: 2012-12

Locations

US (100); CA (8)