Symptoms and General Pathology

All Conditions

Substance Related Disorders

Behaviors and Mental Disorders

Rare Diseases

Constipation

Pain

Opioid-Induced Constipation

Signs and Symptoms, Digestive

Narcotic-Related Disorders

Substance-Related Disorders

Chemically-Induced Disorders

Mental Disorders

Psychotic Disorders

Chronic Graft Versus Host Disease

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Gastrointestinal Agents

Analgesics, Opioid

Linaclotide

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.

Linaclotide 145 micrograms

Linaclotide 290 micrograms

Placebo

Patricia D'Astoli, RN

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.

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

A Phase 2 Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial of Linaclotide Administered Orally for 8 Weeks to Adult Outpatients With Opioid-Induced Constipation Receiving Chronic Opioid Treatment for Non-Cancer Pain

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

The median time to the first SBM after the first dose of investigational product

A 6/8 Week SBM 3 + 1 responder was a participant who met the weekly SBM 3 + 1 responder criteria for at least 6 out of the 8 weeks of the Treatment Period. For each week in the Treatment Period, a weekly SBM 3 + 1 responder was a patient who had an SBM weekly rate ≥ 3 and an increase ≥ 1 in the SBM weekly rate from baseline for that week.

Stool Consistency was assessed using the 7-Point Bristol Stool Form Scale:

1. = separate hard lumps like nuts (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
7. = watery, no solid pieces (entirely liquid)

Straining was measured on a 5-point ordinal scale where a value of 1 is "not at all" and a value of 5 is "an extreme amount."

Abdominal bloating was collected daily via IVRS calls and measured using an 11-point numerical rating scale, where 0 represents no abdominal bloating and 10 represents very severe abdominal bloating.

Ironwood Pharmaceuticals, Inc.

Forest Laboratories

Linaclotide 145 Micrograms

Linaclotide 290 Micrograms

Total

Age, Continuous

Age, Customized

Sex/Gender, Customized

Race

Race/Ethnicity, Customized

Ethnicity

Weight

Height

Body Mass Index (BMI)

Number of spontaneous bowel movements (SBMs) per week

SBM Frequency Rate

Of the 254 participants who were randomized to treatment, 2 patients were randomized in error and did not receive investigational product. 252 of the randomized participants did receive investigational product and comprise the Safety and ITT populations.

Therapeutic Area Head

252 participants received at least one dose of study drug, comprising the ITT study population.

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

Time to First SBM After the First Dose of Investigational Product

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

Of the 252 participants in the ITT population, 200 participants had Stool Consistency data collected

Change From Baseline in 8-Week Stool Consistency

Of the 252 participants in the ITT population, 200 participants had 8-week straining data collected

Spots Global Cancer Trial Database for linaclotide 290 micrograms