Dose-range-finding, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Chronic Constipation

A Randomized, Multicenter, Double-blind, Placebo-controlled, Dose-range-finding, Parallel-group, Phase 2 Trial of Oral Linaclotide Acetate Administered to Patients With Chronic Constipation

The primary purpose of this study is to evaluate the efficacy and safety of administration of linaclotide acetate in patients with chronic constipation.

Study Overview

• Status: Completed
• Conditions: Chronic Constipation
• Intervention / Treatment: Drug: Matching placebo; Drug: linaclotide acetate

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Microbia Investigational Site
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Microbia Investigational Site
  • Arkansas
    • Sherwood, Arkansas, United States, 72120
      • Microbia Investigational Site
  • California
    • Anaheim, California, United States
      • Microbia Investigational Site
    • Sacramento, California, United States
      • Microbia Investigational Site
    • San Diego, California, United States
      • Microbia Investigational Site
  • Colorado
    • Boulder, Colorado, United States
      • Microbia Investigational Site
  • Connecticut
    • Bristol, Connecticut, United States, 06011
      • Microbia Investigational Site
  • Florida
    • Boynton Beach, Florida, United States
      • Microbia Investigational Site
    • Port Orange, Florida, United States
      • Microbia Investigational Site
    • Tampa, Florida, United States
      • Microbia Investigational Site
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Microbia Investigational Site
  • Illinois
    • Peoria, Illinois, United States, 61602
      • Microbia Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Microbia Investigational Site
  • Iowa
    • Clive, Iowa, United States
      • Microbia Investigational Site
    • Davenport, Iowa, United States
      • Microbia Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States
      • Microbia Investigational Site
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Microbia Investigational Site
  • Maryland
    • Silver Spring, Maryland, United States, 20901
      • Microbia Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States
      • Microbia Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States
      • Microbia Investigational Site
    • Traverse City, Michigan, United States, 49684
      • Microbia Investigational Site
  • Mississippi
    • Olive Branch, Mississippi, United States
      • Microbia Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States
      • Microbia Investigational Site
  • New York
    • Great Neck, New York, United States
      • Microbia Investigational Site
    • Pittsford, New York, United States
      • Microbia Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Microbia Investigational Site
    • Chapel Hill, North Carolina, United States, 9199668328
      • Microbia Investigational Site
    • Charlotte, North Carolina, United States, 28075
      • Microbia Investigational Site
    • Fayetteville, North Carolina, United States
      • Microbia Investigational Site
    • Greensboro, North Carolina, United States
      • Microbia Investigational Site
    • Raleigh, North Carolina, United States, 27612
      • Microbia Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Microbia Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Microbia Investigational Site
    • Dayton, Ohio, United States, 45440
      • Microbia Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Microbia Investigational Site
    • Oklahoma City, Oklahoma, United States, 73112
      • Microbia Investigational Site
    • Oklahoma City, Oklahoma, United States, 73116
      • Microbia Investigational Site
    • Tulsa, Oklahoma, United States, 74104
      • Microbia Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
      • Microbia Investigational Site
    • Sellersville, Pennsylvania, United States
      • Microbia Investigational Site
  • South Carolina
    • Anderson, South Carolina, United States
      • Microbia Investigational Site
    • Columbia, South Carolina, United States
      • Microbia Investigational Site
    • Simpsonville, South Carolina, United States
      • Microbia Investigational Site
    • Summerville, South Carolina, United States, 29485
      • Microbia Investigational Site
  • Tennessee
    • Bristol, Tennessee, United States
      • Microbia Investigational Site
    • Chattanooga, Tennessee, United States
      • Microbia Investigational Site
    • Germantown, Tennessee, United States
      • Microbia Investigational Site
    • Jackson, Tennessee, United States, 38301
      • Microbia Investigational Site
  • Texas
    • Austin, Texas, United States, 78745
      • Microbia Investigational Site
    • Corsicana, Texas, United States, 75110
      • Microbia Investigational Site
    • El Paso, Texas, United States
      • Microbia Investigational Site
    • San Antonio, Texas, United States
      • Microbia Investigational Site
  • Utah
    • Ogden, Utah, United States
      • Microbia Investigational Site
  • Virginia
    • Chesapeake, Virginia, United States, 23320
      • Microbia Investigational Site
    • Lynchburg, Virginia, United States, 24502
      • Microbia Investigational Site
  • Washington
    • Olympia, Washington, United States
      • Microbia Investigational Site
    • Spokane, Washington, United States
      • Microbia Investigational Site
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Microbia Investigational Site
    • Madison, Wisconsin, United States
      • Microbia Investigational 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:

• Patient is 18 years of age or older
• Patient meets colonoscopy requirements according to the American Gastroenterological Association
• Patient meets criteria for chronic constipation including weekly bowel movement frequency requirements and reports one or more symptoms of constipation according to protocol requirements
• Patient has successfully completed study requirements with no clinically-significant findings: physical exam, ECG, clinical laboratory tests
• Patient is fluent in English

Exclusion Criteria:

• Patient reports loose or watery stools
• Patient meets criteria for IBS including protocol-defined abdominal discomfort or pain
• Patient may not take prohibited medications per protocol
• Medical diagnoses, medical conditions, or family history that would not make the patient a good candidate for the study or limit the patient's ability to complete the clinical study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Matching Placebo	Drug: Matching placebo; oral, once daily
Active Comparator: 72 ug linaclotide acetate	Drug: linaclotide acetate; oral, once daily.
Active Comparator: 145 ug linaclotide acetate	Drug: linaclotide acetate; oral, once daily.
Active Comparator: 290 ug linaclotide acetate	Drug: linaclotide acetate; oral, once daily.
Active Comparator: 579 ug linaclotide acetate	Drug: linaclotide acetate; oral, once daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Pretreatment in Weekly Normalized Spontaneous Bowel Movement (SBM) Frequency	Change in SBM frequency during Weeks 1 through 4 of the treatment period from the weekly SBM rate obtained during the pretreatment period.	Change from Baseline to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SBM 75% Responder for the Treatment Period (Based on the Normalized Rate)	A patient was an SBM 75% Responder if the patient was an SBM Responder for ≥3 of the 4 treatment period weeks. For each week of the treatment and postreatment periods, a patient was considered an SBM Responder if for that week the patient 1) completed ≥4 days of IVRS questions,2) had an SBM rate of ≥ 3 for the week, and 3) had an increase in SBM rate of ≥ 1 from their baseline weekly SBM rate.	Change from Baseline to Week 4
CSBM 75% Responder for the Treatment Period (Based on the Normalized Rate)	A patient was a complete spontaneous bowel movement (CSBM) 75% Responder if the patient was a CSBM Responder for ≥3 of the 4 treatment period weeks. For each week of the treatment and postreatment periods, a patient was considered a CSBM Responder if for that week the patient 1) completed ≥4 days of IVRS questions,2) had a CSBM rate of ≥ 3 for the week, and 3) had an increase in CSBM rate of ≥ 1 from their baseline weekly CSBM rate.	Change from Baseline to Week 4
Change From Baseline in the Weekly Normalized CSBM Rate for the Treatment Period	CSBMs measured daily during the treatment period. During each daily phone call into the IVRS, patients were asked: How many bowel movements did you have today or yesterday after your last call?	Change from Baseline to Week 4
Change From Baseline in Stool Consistency (BSFS) Score for the Treatment Period	Stool consistency analyses were performed using the 7-point BSFS, whereby a score of 1 = difficult to pass; 2 = sausage shaped but lumpy; 3 = like a sausage but with cracks on surface; 4 = like a sausage or snake, smooth and soft; 5 = soft blobs with clear-cut edges (passed easily); 6 = fluffy pieces with ragged edges, a mushy stool; and 7 = entirely liquid.	Change from Baseline to Week 4
Change From Baseline in Straining Score for the Treatment Period	Straining was assessed using a 5-point ordinal scale, whereby a score of 1 = not at all, 2 = a little bit, 3 = a moderate amount, 4 = a great deal, and 5 = an extreme amount.	Change from Baseline to Week 4

Collaborators and Investigators

• Sponsor: Ironwood Pharmaceuticals, Inc.
• Investigators: Study Director: Microbia Medical Affairs, Microbia, Inc.

Publications and helpful links

General Publications

• Lembo AJ, Kurtz CB, Macdougall JE, Lavins BJ, Currie MG, Fitch DA, Jeglinski BI, Johnston JM. Efficacy of linaclotide for patients with chronic constipation. Gastroenterology. 2010 Mar;138(3):886-95.e1. doi: 10.1053/j.gastro.2009.12.050. Epub 2010 Jan 4.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: November 18, 2006
• First Submitted That Met QC Criteria: November 20, 2006
• First Posted (Estimate): November 22, 2006

Study Record Updates

• Last Update Posted (Estimate): March 5, 2013
• Last Update Submitted That Met QC Criteria: January 29, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Constipation; Chronic Constipation; linaclotide; MD-1100; linaclotide acetate; Microbia
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Guanylyl Cyclase C Agonists; Enzyme Activators; Linaclotide
• Other Study ID Numbers: MCP-103-201