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

Forest Laboratories

Status and phase

Completed

Phase 2

Conditions

Opioid-Induced Constipation

Treatments

Drug: Placebo

Drug: Linaclotide 290 micrograms

Drug: Linaclotide 145 micrograms

Study type

Interventional

Funder types

Industry

Identifiers

NCT02270983

LIN-MD-40

Details and patient eligibility

About

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.

Enrollment

254 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

254 participants in 3 patient groups

Linaclotide 145 micrograms

Experimental group

Description:

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.

Treatment:

Drug: Linaclotide 145 micrograms

Linaclotide 290 micrograms

Experimental group

Description:

Treatment:

Drug: Linaclotide 290 micrograms

Placebo

Experimental group

Description:

Treatment:

Drug: Placebo