Clinical trial NCT02270983: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Opioid-Induced Constipation
Keywords: Opioid-Induced Constipation
Linaclotide
Linzess
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
Collaborators: name: Ironwood Pharmaceuticals, Inc.
First posted: 2014-10-22
Enrollment: 254
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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): \< 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

Primary outcomes:
measure: Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week)
timeFrame: Baseline (Week 0) to Week 8
Secondary outcomes:
measure: Time to First SBM After the First Dose of Investigational Product
timeFrame: Baseline (Day 0) up to 8 weeks
measure: Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria
timeFrame: 8-week treatment period
measure: Change From Baseline in 8-Week Stool Consistency
timeFrame: Baseline (Week 0) to Week 8
measure: Change From Baseline in 8-Week Straining
timeFrame: Baseline (Week 0) to Week 8
measure: Change From Baseline in 8-Week Abdominal Bloating
timeFrame: Baseline (Week 0) to Week 8
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Forest Investigative Site 002
state: Alabama
city: Foley
country: United States
facility: Forest Investigative Site 001
state: Alabama
city: Phoenix
country: United States
facility: Forest Investigative Site 007
state: Arizona
city: Tucson
country: United States
facility: Forest Investigative Site 008
state: Arizona
city: North Little Rock
country: United States
facility: Forest Investigative Site 003
state: Arkansas
city: Anaheim
country: United States
facility: Forest Investigative Site 018
state: California
city: Fountain Valley
country: United States
facility: Forest Investigative Site 014
state: California
city: Fresno
country: United States
facility: Forest Investigative Site 019
state: California
city: Garden Grove
country: United States
facility: Forest Investigative Site 017
state: California
city: Gold River
country: United States
facility: Forest Investigative Site 010
state: California
city: Lincoln
country: United States
facility: Forest Investigative Site 009
state: California
city: North Hollywood
country: United States
facility: Forest Investigative Site 012
state: California
city: Orange
country: United States
facility: Forest Investigative Site 011
state: California
city: Sacramento
country: United States
facility: Forest Investigative Site 016
state: California
city: San Diego
country: United States
facility: Forest Investigative Site 013
state: California
city: Santa Ana
country: United States
facility: Forest Investigative Site 015
state: California
city: Colorado Springs
country: United States
facility: Forest Investigative Site 020
state: Colorado
city: Bristol
country: United States
facility: Forest Investigative Site 021
state: Connecticut
city: Boynton Beach
country: United States
facility: Forest Investigative Site 035
state: Florida
city: Bradenton
country: United States
facility: Forest Investigative Site 038
state: Florida
city: DeLand
country: United States
facility: Forest Investigative Site 024
state: Florida
city: Gainesville
country: United States
facility: Forest Investigative Site 027
state: Florida
city: Jacksonville
country: United States
facility: Forest Investigative Site 023
state: Florida
city: Jupiter
country: United States
facility: Forest Investigative Site 036
state: Florida
city: Lauderdale Lakes
country: United States
facility: Forest Investigative Site 037
state: Florida
city: Miami
country: United States
facility: Forest Investigative Site 028
state: Florida
city: Orlando
country: United States
facility: Forest Investigative Site 040
state: Florida
city: Oviedo
country: United States
facility: Forest Investigative Site 022
state: Florida
city: Port Orange
country: United States
facility: Forest Investigative Site 034
state: Florida
city: Seminole
country: United States
facility: Forest Investigative Site 029
state: Florida
city: Tampa
country: United States
facility: Forest Investigative Site 031
state: Florida
city: Tampa
country: United States
facility: Forest Investigative Site 033
state: Florida
city: Tampa
country: United States
facility: Forest Investigative Site 030
state: Florida
city: West Palm Beach
country: United States
facility: Forest Investigative Site 039
state: Florida
city: Weston
country: United States
facility: Forest Investigative Site 032
state: Florida
city: Marietta
country: United States
facility: Forest Investigative Site 041
state: Georgia
city: Woodstock
country: United States
facility: Forest Investigative Site 042
state: Georgia
city: Chicago
country: United States
facility: Forest Investigative Site 043
state: Illinois
city: Evansville
country: United States
facility: Forest Investigative Site 044
state: Indiana
city: Madisonville
country: United States
facility: Forest Investigative Site 045
state: Kentucky
city: Metairie
country: United States
facility: Forest Investigative Site 046
state: Louisiana
city: Hagerstown
country: United States
facility: Forest Investigative Site 048
state: Maryland
city: Watertown
country: United States
facility: Forest Investigative Site 047
state: Massachusetts
city: Chesterfield
country: United States
facility: Forest Investigative Site 050
state: Michigan
city: Flint
country: United States
facility: Forest Investigative Site 049
state: Michigan
city: Omaha
country: United States
facility: Forest Investigative Site 058
state: Nebraska
city: Omaha
country: United States
facility: Forest Investigative Site 057
state: Nebraska
city: Williamsville
country: United States
facility: Forest Investigative Site 059
state: New York
city: Asheboro
country: United States
facility: Forest Investigative Site 082
state: North Carolina
city: Chapel Hill
country: United States
facility: Forest Investigative Site 054
state: North Carolina
city: Davidson
country: United States
facility: Forest Investigative Site 088
state: North Carolina
city: Flat Rock
country: United States
facility: Forest Investigative Site 051
state: North Carolina
city: Greensboro
country: United States
facility: Forest Investigative Site 052
state: North Carolina
city: Greensboro
country: United States
facility: Forest Investigative Site 055
state: North Carolina
city: Winston-Salem
country: United States
facility: Forest Investigative Site 053
state: North Carolina
city: Fargo
country: United States
facility: Forest Investigative Site 056
state: North Dakota
city: Cincinnati
country: United States
facility: Forest Investigative Site 062
state: Ohio
city: Columbus
country: United States
facility: Forest Investigative Site 061
state: Ohio
city: Mentor
country: United States
facility: Forest Investigative Site 060
state: Ohio
city: Wadsworth
country: United States
facility: Forest Investigative Site 087
state: Ohio
city: Oklahoma City
country: United States
facility: Forest Investigative Site 064
state: Oklahoma
city: Oklahoma City
country: United States
facility: Forest Investigative Site 063
state: Oklahoma
city: Tulsa
country: United States
facility: Forest Investigative Site 065
state: Oklahoma
city: Medford
country: United States
facility: Forest Investigative Site 066
state: Oregon
city: Levittown
country: United States
facility: Forest Investigative Site 067
state: Pennsylvania
city: Philadelphia
country: United States
facility: Forest Investigative Site 080
state: Pennsylvania
city: Cumberland
country: United States
facility: Forest Investigative Site 068
state: Rhode Island
city: Charleston
country: United States
facility: Forest Investigative Site 070
state: South Carolina
city: Richardson
country: United States
facility: Forest Investigative Site 083
state: Texas
city: San Antonio
country: United States
facility: Forest Investigative Site 074
state: Texas
city: San Antonio
country: United States
facility: Forest Investigative Site 073
state: Texas
city: San Antonio
country: United States
facility: Forest Investigative Site 071
state: Texas
city: Logan
country: United States
facility: Forest Investigative Site 075
state: Utah
city: Ogden
country: United States
facility: Forest Investigative Site 084
state: Utah
city: West Jordan
country: United States
facility: Forest Investigative Site 076
state: Utah
city: Christiansburg
country: United States
facility: Forest Investigative Site 078
state: Virginia
city: Bellevue
country: United States
facility: Forest Investigative Site 079
state: Washington
Study officials:
affiliation: Forest Laboratories, LLC, an Allergan Affiliate
name: Patricia D'Astoli, RN
role: STUDY_DIRECTOR
References:
citation: 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.