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

NCT02270983 | Completed Phase 2 Results

• 1 other identifier: LIN-MD-40
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 77

Brief Summary

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.

Conditions

Opioid-Induced Constipation

Keywords

Opioid-Induced Constipation; Linaclotide; Linzess

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week)

  Change from baseline in 8-Week SBM frequency rate (SBMs/week) during the Treatment Period.

  Baseline (Week 0) to Week 8

Secondary Outcomes (5)

• Time to First SBM After the First Dose of Investigational Product

  Baseline (Day 0) up to 8 weeks

• Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria

  8-week treatment period

• Change From Baseline in 8-Week Stool Consistency

  Baseline (Week 0) to Week 8

• Change From Baseline in 8-Week Straining

  Baseline (Week 0) to Week 8

• Change From Baseline in 8-Week Abdominal Bloating

  Baseline (Week 0) to Week 8

Study Arms (3)

Linaclotide 145 micrograms

EXPERIMENTAL

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.

Drug: Linaclotide 145 micrograms

Linaclotide 290 micrograms

EXPERIMENTAL

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.

Drug: Linaclotide 290 micrograms

Placebo

EXPERIMENTAL

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.

Drug: Placebo

Interventions

Linaclotide 145 micrograms DRUG

Also known as: Linzess

Linaclotide 145 micrograms

Linaclotide 290 micrograms DRUG

Also known as: Linzess

Linaclotide 290 micrograms

Placebo DRUG

Matching placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• 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:
• Straining during \> 25% of BMs
• Lumpy or hard stools during \> 25% of BMs
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (77)

Forest Investigative Site 002

Anniston, Alabama, 36207, United States

Location

Forest Investigative Site 001

Foley, Alabama, 36535, United States

Location

Forest Investigative Site 007

Phoenix, Arizona, 85029, United States

Location

Forest Investigative Site 008

Tucson, Arizona, 85710, United States

Location

Forest Investigative Site 003

North Little Rock, Arkansas, 72217, United States

Location

Forest Investigative Site 018

Anaheim, California, 92801, United States

Location

Forest Investigative Site 014

Fountain Valley, California, 92708, United States

Location

Forest Investigative Site 019

Fresno, California, 93702, United States

Location

Forest Investigative Site 017

Garden Grove, California, 92843, United States

Location

Forest Investigative Site 010

Gold River, California, 95670, United States

Location

Forest Investigative Site 009

Lincoln, California, 95648, United States

Location

Forest Investigative Site 012

North Hollywood, California, 91606, United States

Location

Forest Investigative Site 011

Orange, California, 92868, United States

Location

Forest Investigative Site 016

Sacramento, California, 95821, United States

Location

Forest Investigative Site 013

San Diego, California, 92108, United States

Location

Forest Investigative Site 015

Santa Ana, California, 92701, United States

Location

Forest Investigative Site 020

Colorado Springs, Colorado, 80904, United States

Location

Forest Investigative Site 021

Bristol, Connecticut, 06010, United States

Location

Forest Investigative Site 035

Boynton Beach, Florida, 33426, United States

Location

Forest Investigative Site 038

Bradenton, Florida, 34208, United States

Location

Forest Investigative Site 024

DeLand, Florida, 32720, United States

Location

Forest Investigative Site 027

Gainesville, Florida, 32607, United States

Location

Forest Investigative Site 023

Jacksonville, Florida, 32257, United States

Location

Forest Investigative Site 036

Jupiter, Florida, 33458, United States

Location

Forest Investigative Site 037

Lauderdale Lakes, Florida, 33319, United States

Location

Forest Investigative Site 028

Miami, Florida, 33185, United States

Location

Forest Investigative Site 040

Orlando, Florida, 32801, United States

Location

Forest Investigative Site 022

Oviedo, Florida, 32765, United States

Location

Forest Investigative Site 034

Port Orange, Florida, 32129, United States

Location

Forest Investigative Site 029

Seminole, Florida, 33777, United States

Location

Forest Investigative Site 031

Tampa, Florida, 33603, United States

Location

Forest Investigative Site 033

Tampa, Florida, 33606, United States

Location

Forest Investigative Site 030

Tampa, Florida, 33613, United States

Location

Forest Investigative Site 039

West Palm Beach, Florida, 33409, United States

Location

Forest Investigative Site 032

Weston, Florida, 33331, United States

Location

Forest Investigative Site 041

Marietta, Georgia, 30060, United States

Location

Forest Investigative Site 042

Woodstock, Georgia, 30189, United States

Location

Forest Investigative Site 043

Chicago, Illinois, 60616, United States

Location

Forest Investigative Site 044

Evansville, Indiana, 47714, United States

Location

Forest Investigative Site 045

Madisonville, Kentucky, 42431, United States

Location

Forest Investigative Site 046

Metairie, Louisiana, 70006, United States

Location

Forest Investigative Site 048

Hagerstown, Maryland, 21742, United States

Location

Forest Investigative Site 047

Watertown, Massachusetts, 02472, United States

Location

Forest Investigative Site 050

Chesterfield, Michigan, 48047, United States

Location

Forest Investigative Site 049

Flint, Michigan, 48504, United States

Location

Forest Investigative Site 058

Omaha, Nebraska, 68114, United States

Location

Forest Investigative Site 057

Omaha, Nebraska, 68134, United States

Location

Forest Investigative Site 059

Williamsville, New York, 14221, United States

Location

Forest Investigative Site 082

Asheboro, North Carolina, 27203, United States

Location

Forest Investigative Site 054

Chapel Hill, North Carolina, 27514, United States

Location

Forest Investigative Site 088

Davidson, North Carolina, 28036, United States

Location

Forest Investigative Site 051

Flat Rock, North Carolina, 28731, United States

Location

Forest Investigative Site 052

Greensboro, North Carolina, 27403, United States

Location

Forest Investigative Site 055

Greensboro, North Carolina, 27410, United States

Location

Forest Investigative Site 053

Winston-Salem, North Carolina, 27103, United States

Location

Forest Investigative Site 056

Fargo, North Dakota, 58103, United States

Location

Forest Investigative Site 062

Cincinnati, Ohio, 45219, United States

Location

Forest Investigative Site 061

Columbus, Ohio, 43213, United States

Location

Forest Investigative Site 060

Mentor, Ohio, 44060, United States

Location

Forest Investigative Site 087

Wadsworth, Ohio, 44281, United States

Location

Forest Investigative Site 064

Oklahoma City, Oklahoma, 73103, United States

Location

Forest Investigative Site 063

Oklahoma City, Oklahoma, 73120, United States

Location

Forest Investigative Site 065

Tulsa, Oklahoma, 74104, United States

Location

Forest Investigative Site 066

Medford, Oregon, 97504, United States

Location

Forest Investigative Site 067

Levittown, Pennsylvania, 19056, United States

Location

Forest Investigative Site 080

Philadelphia, Pennsylvania, 19140, United States

Location

Forest Investigative Site 068

Cumberland, Rhode Island, 02864, United States

Location

Forest Investigative Site 070

Charleston, South Carolina, 29406, United States

Location

Forest Investigative Site 083

Richardson, Texas, 75080, United States

Location

Forest Investigative Site 074

San Antonio, Texas, 78209, United States

Location

Forest Investigative Site 073

San Antonio, Texas, 78215, United States

Location

Forest Investigative Site 071

San Antonio, Texas, 78229, United States

Location

Forest Investigative Site 075

Logan, Utah, 84341, United States

Location

Forest Investigative Site 084

Ogden, Utah, 84341, United States

Location

Forest Investigative Site 076

West Jordan, Utah, 84088, United States

Location

Forest Investigative Site 078

Christiansburg, Virginia, 24073, United States

Location

Forest Investigative Site 079

Bellevue, Washington, 98007, United States

Location

Related Publications (1)

• 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.

  PMID: 32310620 DERIVED

MeSH Terms

Conditions

Opioid-Induced Constipation

Interventions

linaclotide

Condition Hierarchy (Ancestors)

Constipation; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Forest Research Institute, Inc., an affiliate of Allergan

IR-CTRegistration@allergan.com

862-261-7000

Study Officials

• Patricia D'Astoli, RN

  Forest Laboratories, LLC, an Allergan Affiliate

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• 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 16, 2014
• First Posted: October 22, 2014
• Study Start: October 31, 2014
• Primary Completion: August 31, 2015
• Study Completion: October 31, 2015
• Last Updated: April 8, 2019
• Results First Posted: April 8, 2019

Record last verified: 2019-04

Locations

US (77)