Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered to Patients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain

NCT ID: NCT02270983

Last Updated: 2019-04-08

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

254 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2015-10-31

Brief Summary

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The purpose of this study was to evaluate the safety and efficacy of linaclotide for the treatment of opioid-induced constipation (OIC), in adults receiving stable opioid treatment for chronic non-cancer pain that has been present for a minimum of 3 months.

This study included up to a 4-week Screening Period, and a 2 to 3-week Pretreatment Period. Patients meeting the entry criteria were randomized to 1 of 2 doses of linaclotide or placebo once per day for 8 weeks. This 8-week study assessed the effects of linaclotide on bowel movement frequency, as well as other bowel symptoms of OIC.

Detailed Description

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Conditions

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Opioid-Induced Constipation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Linaclotide 145 micrograms

Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.

Group Type EXPERIMENTAL

Linaclotide 145 micrograms

Intervention Type DRUG

Linaclotide 290 micrograms

Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.

Group Type EXPERIMENTAL

Linaclotide 290 micrograms

Intervention Type DRUG

Placebo

Oral capsule, taken once daily each morning at least 30 minutes before breakfast, with the exception of the first Treatment Period dose which will be taken at the study center after at least a 2-hour fast.

Group Type EXPERIMENTAL

Placebo

Intervention Type DRUG

Matching placebo

Interventions

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Linaclotide 145 micrograms

Intervention Type DRUG

Linaclotide 290 micrograms

Intervention Type DRUG

Placebo

Matching placebo

Intervention Type DRUG

Other Intervention Names

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Linzess Linzess

Eligibility Criteria

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Inclusion Criteria

* Patient has chronic non-cancer pain that has been present for a minimum of 3 months
* Patient has been receiving a stable oral dose of a full-opioid agonist for at least 4 days per week during the 8 consecutive weeks
* Patient meets protocol criteria for Opioid-Induced Constipation (OIC): \< 3 spontaneous bowel movements (SBMs) per week and reports one of the following symptoms for at least 4 weeks:

1. Straining during \> 25% of BMs
2. Lumpy or hard stools during \> 25% of BMs
3. Sensation of incomplete evacuation during \> 25% of BMs
* Patient meets the colonoscopy requirements defined by the American Gastroenterological Association guidelines
* Patient has successfully completed protocol procedures (with no clinically significant findings)
* Patient is compliant with Interactive Voice Response System (IVRS) for daily diary reporting
* Patient has a total of \< 6 SBMs in IVRS during the 14 days before and up to the time of Randomization
* Patient has adequate relief and well-controlled pain with current dose of opioid

Exclusion Criteria

* Patient has been using opioids for abdominal pain
* Patient has symptoms of or been diagnosed with chronic constipation or chronic idiopathic constipation prior to initiation of opioid treatment
* Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS) prior to initiation of opioid treatment
* Patient has a history of loose or watery stools for \> 25% of BMs during the 3 months before the Screening in the absence of laxatives, suppositories, or enemas
* 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 would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ironwood Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role collaborator

Forest Laboratories

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patricia D'Astoli, RN

Role: STUDY_DIRECTOR

Forest Laboratories, LLC, an Allergan Affiliate

Locations

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Forest Investigative Site 002

Anniston, Alabama, United States

Site Status

Forest Investigative Site 001

Foley, Alabama, United States

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Forest Investigative Site 007

Phoenix, Arizona, United States

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Forest Investigative Site 008

Tucson, Arizona, United States

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Forest Investigative Site 003

North Little Rock, Arkansas, United States

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Forest Investigative Site 018

Anaheim, California, United States

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Forest Investigative Site 014

Fountain Valley, California, United States

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Forest Investigative Site 019

Fresno, California, United States

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Forest Investigative Site 017

Garden Grove, California, United States

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Forest Investigative Site 010

Gold River, California, United States

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Forest Investigative Site 009

Lincoln, California, United States

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Forest Investigative Site 012

North Hollywood, California, United States

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Forest Investigative Site 011

Orange, California, United States

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Forest Investigative Site 016

Sacramento, California, United States

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Forest Investigative Site 013

San Diego, California, United States

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Forest Investigative Site 015

Santa Ana, California, United States

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Forest Investigative Site 020

Colorado Springs, Colorado, United States

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Forest Investigative Site 021

Bristol, Connecticut, United States

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Forest Investigative Site 035

Boynton Beach, Florida, United States

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Forest Investigative Site 038

Bradenton, Florida, United States

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Forest Investigative Site 024

DeLand, Florida, United States

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Forest Investigative Site 027

Gainesville, Florida, United States

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Forest Investigative Site 023

Jacksonville, Florida, United States

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Forest Investigative Site 036

Jupiter, Florida, United States

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Forest Investigative Site 037

Lauderdale Lakes, Florida, United States

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Forest Investigative Site 028

Miami, Florida, United States

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Forest Investigative Site 040

Orlando, Florida, United States

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Forest Investigative Site 022

Oviedo, Florida, United States

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Forest Investigative Site 034

Port Orange, Florida, United States

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Forest Investigative Site 029

Seminole, Florida, United States

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Forest Investigative Site 031

Tampa, Florida, United States

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Forest Investigative Site 033

Tampa, Florida, United States

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Forest Investigative Site 030

Tampa, Florida, United States

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Forest Investigative Site 039

West Palm Beach, Florida, United States

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Forest Investigative Site 032

Weston, Florida, United States

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Forest Investigative Site 041

Marietta, Georgia, United States

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Forest Investigative Site 042

Woodstock, Georgia, United States

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Forest Investigative Site 043

Chicago, Illinois, United States

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Forest Investigative Site 044

Evansville, Indiana, United States

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Forest Investigative Site 045

Madisonville, Kentucky, United States

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Forest Investigative Site 046

Metairie, Louisiana, United States

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Forest Investigative Site 048

Hagerstown, Maryland, United States

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Forest Investigative Site 047

Watertown, Massachusetts, United States

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Forest Investigative Site 050

Chesterfield, Michigan, United States

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Forest Investigative Site 049

Flint, Michigan, United States

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Forest Investigative Site 058

Omaha, Nebraska, United States

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Forest Investigative Site 057

Omaha, Nebraska, United States

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Forest Investigative Site 059

Williamsville, New York, United States

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Forest Investigative Site 082

Asheboro, North Carolina, United States

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Forest Investigative Site 054

Chapel Hill, North Carolina, United States

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Forest Investigative Site 088

Davidson, North Carolina, United States

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Forest Investigative Site 051

Flat Rock, North Carolina, United States

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Forest Investigative Site 052

Greensboro, North Carolina, United States

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Forest Investigative Site 055

Greensboro, North Carolina, United States

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Forest Investigative Site 053

Winston-Salem, North Carolina, United States

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Forest Investigative Site 056

Fargo, North Dakota, United States

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Forest Investigative Site 062

Cincinnati, Ohio, United States

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Forest Investigative Site 061

Columbus, Ohio, United States

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Forest Investigative Site 060

Mentor, Ohio, United States

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Forest Investigative Site 087

Wadsworth, Ohio, United States

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Forest Investigative Site 064

Oklahoma City, Oklahoma, United States

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Forest Investigative Site 063

Oklahoma City, Oklahoma, United States

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Forest Investigative Site 065

Tulsa, Oklahoma, United States

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Forest Investigative Site 066

Medford, Oregon, United States

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Forest Investigative Site 067

Levittown, Pennsylvania, United States

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Forest Investigative Site 080

Philadelphia, Pennsylvania, United States

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Forest Investigative Site 068

Cumberland, Rhode Island, United States

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Forest Investigative Site 070

Charleston, South Carolina, United States

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Forest Investigative Site 083

Richardson, Texas, United States

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Forest Investigative Site 074

San Antonio, Texas, United States

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Forest Investigative Site 073

San Antonio, Texas, United States

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Forest Investigative Site 071

San Antonio, Texas, United States

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Forest Investigative Site 075

Logan, Utah, United States

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Forest Investigative Site 084

Ogden, Utah, United States

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Forest Investigative Site 076

West Jordan, Utah, United States

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Forest Investigative Site 078

Christiansburg, Virginia, United States

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Forest Investigative Site 079

Bellevue, Washington, United States

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Countries

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United States

References

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Brenner DM, Argoff CE, Fox SM, Bochenek W, D'Astoli P, Blakesley RE, Reasner DS, O'Dea CR, Cash BD. Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study. Pain. 2020 May;161(5):1027-1036. doi: 10.1097/j.pain.0000000000001754.

Reference Type DERIVED
PMID: 32310620 (View on PubMed)

Other Identifiers

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LIN-MD-40

Identifier Type: -

Identifier Source: org_study_id

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