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 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02270983
• Other study ID #: LIN-MD-40
• Status: Completed
• Phase: Phase 2
• Start date: October 31, 2014
• Est. completion date: October 31, 2015

Study information

• Verified date: April 2019
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 254
• Est. completion date: October 31, 2015
• Est. primary completion date: August 31, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Constipation
• Opioid-Induced Constipation

Intervention

Drug:
• Linaclotide 145 micrograms

• Linaclotide 290 micrograms

• Placebo
Matching placebo

Locations

Country	Name	City	State
United States	Forest Investigative Site 018	Anaheim	California
United States	Forest Investigative Site 002	Anniston	Alabama
United States	Forest Investigative Site 082	Asheboro	North Carolina
United States	Forest Investigative Site 079	Bellevue	Washington
United States	Forest Investigative Site 035	Boynton Beach	Florida
United States	Forest Investigative Site 038	Bradenton	Florida
United States	Forest Investigative Site 021	Bristol	Connecticut
United States	Forest Investigative Site 054	Chapel Hill	North Carolina
United States	Forest Investigative Site 070	Charleston	South Carolina
United States	Forest Investigative Site 050	Chesterfield	Michigan
United States	Forest Investigative Site 043	Chicago	Illinois
United States	Forest Investigative Site 078	Christiansburg	Virginia
United States	Forest Investigative Site 062	Cincinnati	Ohio
United States	Forest Investigative Site 020	Colorado Springs	Colorado
United States	Forest Investigative Site 061	Columbus	Ohio
United States	Forest Investigative Site 068	Cumberland	Rhode Island
United States	Forest Investigative Site 088	Davidson	North Carolina
United States	Forest Investigative Site 024	DeLand	Florida
United States	Forest Investigative Site 044	Evansville	Indiana
United States	Forest Investigative Site 056	Fargo	North Dakota
United States	Forest Investigative Site 051	Flat Rock	North Carolina
United States	Forest Investigative Site 049	Flint	Michigan
United States	Forest Investigative Site 001	Foley	Alabama
United States	Forest Investigative Site 014	Fountain Valley	California
United States	Forest Investigative Site 019	Fresno	California
United States	Forest Investigative Site 027	Gainesville	Florida
United States	Forest Investigative Site 017	Garden Grove	California
United States	Forest Investigative Site 010	Gold River	California
United States	Forest Investigative Site 052	Greensboro	North Carolina
United States	Forest Investigative Site 055	Greensboro	North Carolina
United States	Forest Investigative Site 048	Hagerstown	Maryland
United States	Forest Investigative Site 023	Jacksonville	Florida
United States	Forest Investigative Site 036	Jupiter	Florida
United States	Forest Investigative Site 037	Lauderdale Lakes	Florida
United States	Forest Investigative Site 067	Levittown	Pennsylvania
United States	Forest Investigative Site 009	Lincoln	California
United States	Forest Investigative Site 075	Logan	Utah
United States	Forest Investigative Site 045	Madisonville	Kentucky
United States	Forest Investigative Site 041	Marietta	Georgia
United States	Forest Investigative Site 066	Medford	Oregon
United States	Forest Investigative Site 060	Mentor	Ohio
United States	Forest Investigative Site 046	Metairie	Louisiana
United States	Forest Investigative Site 028	Miami	Florida
United States	Forest Investigative Site 012	North Hollywood	California
United States	Forest Investigative Site 003	North Little Rock	Arkansas
United States	Forest Investigative Site 084	Ogden	Utah
United States	Forest Investigative Site 063	Oklahoma City	Oklahoma
United States	Forest Investigative Site 064	Oklahoma City	Oklahoma
United States	Forest Investigative Site 057	Omaha	Nebraska
United States	Forest Investigative Site 058	Omaha	Nebraska
United States	Forest Investigative Site 011	Orange	California
United States	Forest Investigative Site 040	Orlando	Florida
United States	Forest Investigative Site 022	Oviedo	Florida
United States	Forest Investigative Site 080	Philadelphia	Pennsylvania
United States	Forest Investigative Site 007	Phoenix	Arizona
United States	Forest Investigative Site 034	Port Orange	Florida
United States	Forest Investigative Site 083	Richardson	Texas
United States	Forest Investigative Site 016	Sacramento	California
United States	Forest Investigative Site 071	San Antonio	Texas
United States	Forest Investigative Site 073	San Antonio	Texas
United States	Forest Investigative Site 074	San Antonio	Texas
United States	Forest Investigative Site 013	San Diego	California
United States	Forest Investigative Site 015	Santa Ana	California
United States	Forest Investigative Site 029	Seminole	Florida
United States	Forest Investigative Site 030	Tampa	Florida
United States	Forest Investigative Site 031	Tampa	Florida
United States	Forest Investigative Site 033	Tampa	Florida
United States	Forest Investigative Site 008	Tucson	Arizona
United States	Forest Investigative Site 065	Tulsa	Oklahoma
United States	Forest Investigative Site 087	Wadsworth	Ohio
United States	Forest Investigative Site 047	Watertown	Massachusetts
United States	Forest Investigative Site 076	West Jordan	Utah
United States	Forest Investigative Site 039	West Palm Beach	Florida
United States	Forest Investigative Site 032	Weston	Florida
United States	Forest Investigative Site 059	Williamsville	New York
United States	Forest Investigative Site 053	Winston-Salem	North Carolina
United States	Forest Investigative Site 042	Woodstock	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Forest Laboratories	Ironwood Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Time to First SBM After the First Dose of Investigational Product	The median time to the first SBM after the first dose of investigational product	Baseline (Day 0) up to 8 weeks
Secondary	Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria	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.	8-week treatment period
Secondary	Change From Baseline in 8-Week Stool Consistency	Stool Consistency was assessed using the 7-Point Bristol Stool Form Scale: = separate hard lumps like nuts (difficult to pass); = sausage shaped but lumpy; = like a sausage but with cracks on surface; = like a sausage or snake, smooth and soft; = soft blobs with clear-cut edges (passed easily); = fluffy pieces with ragged edges, a mushy; = watery, no solid pieces (entirely liquid)	Baseline (Week 0) to Week 8
Secondary	Change From Baseline in 8-Week Straining	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."	Baseline (Week 0) to Week 8
Secondary	Change From Baseline in 8-Week Abdominal Bloating	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.	Baseline (Week 0) to Week 8