Phase 2
N=254
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
Opioid-Induced Constipation
Bottom Line
View on ClinicalTrials.gov: NCT02270983 ↗Enrolled (actual)
254
Serious AEs
2.4%
Results posted
Apr 2019
Primary outcome: Primary: Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week) — 1.474; 2.799; 3.382 Number of SBMs per week — p=0.0035
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Linaclotide 145 micrograms (Drug); Linaclotide 290 micrograms (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Forest Laboratories
- Primary completion
- Aug 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week) |
1.474; 2.799; 3.382 | 0.0035 sig |
| SECONDARY Time to First SBM After the First Dose of Investigational Product |
47.1; 26.5; 28.7 | 0.1429 |
| SECONDARY Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria |
33.3; 40.2; 47.1 | 0.3332 |
| SECONDARY Change From Baseline in 8-Week Stool Consistency |
0.911; 1.662; 1.898 | 0.0007 sig |
| SECONDARY Change From Baseline in 8-Week Straining |
-0.753; -1.212; -1.422 | 0.0017 sig |
| SECONDARY Change From Baseline in 8-Week Abdominal Bloating |
-0.983; -0.950; -1.590 | 0.8720 |
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.
Eligibility Criteria
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): 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 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
Data sourced from ClinicalTrials.gov (NCT02270983). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.