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
- Conditions
- Opioid-Induced Constipation
- Interventions
- Registration Number
- NCT02270983
- Lead Sponsor
- Forest Laboratories
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 254
-
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:
- Straining during > 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 < 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Linaclotide 290 micrograms Linaclotide 290 micrograms 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. Placebo Placebo 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 145 micrograms 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.
- Primary Outcome Measures
Name Time Method Change From Baseline in 8-Week SBM Frequency Rate (SBMs/Week) Baseline (Week 0) to Week 8 Change from baseline in 8-Week SBM frequency rate (SBMs/week) during the Treatment Period.
- Secondary Outcome Measures
Name Time Method Time to First SBM After the First Dose of Investigational Product Baseline (Day 0) up to 8 weeks The median time to the first SBM after the first dose of investigational product
Percentage of Participants Meeting 6/8 Week Spontaneous Bowel Movement (SBM) 3 + 1 Responder Criteria 8-week treatment period 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.
Change From Baseline in 8-Week Stool Consistency Baseline (Week 0) to Week 8 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)Change From Baseline in 8-Week Straining Baseline (Week 0) to Week 8 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."
Change From Baseline in 8-Week Abdominal Bloating Baseline (Week 0) to Week 8 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.
Trial Locations
- Locations (77)
Forest Investigative Site 062
🇺🇸Cincinnati, Ohio, United States
Forest Investigative Site 080
🇺🇸Philadelphia, Pennsylvania, United States
Forest Investigative Site 074
🇺🇸San Antonio, Texas, United States
Forest Investigative Site 073
🇺🇸San Antonio, Texas, United States
Forest Investigative Site 071
🇺🇸San Antonio, Texas, United States
Forest Investigative Site 064
🇺🇸Oklahoma City, Oklahoma, United States
Forest Investigative Site 063
🇺🇸Oklahoma City, Oklahoma, United States
Forest Investigative Site 018
🇺🇸Anaheim, California, United States
Forest Investigative Site 043
🇺🇸Chicago, Illinois, United States
Forest Investigative Site 033
🇺🇸Tampa, Florida, United States
Forest Investigative Site 035
🇺🇸Boynton Beach, Florida, United States
Forest Investigative Site 024
🇺🇸DeLand, Florida, United States
Forest Investigative Site 013
🇺🇸San Diego, California, United States
Forest Investigative Site 003
🇺🇸North Little Rock, Arkansas, United States
Forest Investigative Site 038
🇺🇸Bradenton, Florida, United States
Forest Investigative Site 061
🇺🇸Columbus, Ohio, United States
Forest Investigative Site 007
🇺🇸Phoenix, Arizona, United States
Forest Investigative Site 009
🇺🇸Lincoln, California, United States
Forest Investigative Site 023
🇺🇸Jacksonville, Florida, United States
Forest Investigative Site 055
🇺🇸Greensboro, North Carolina, United States
Forest Investigative Site 037
🇺🇸Lauderdale Lakes, Florida, United States
Forest Investigative Site 050
🇺🇸Chesterfield, Michigan, United States
Forest Investigative Site 019
🇺🇸Fresno, California, United States
Forest Investigative Site 028
🇺🇸Miami, Florida, United States
Forest Investigative Site 008
🇺🇸Tucson, Arizona, United States
Forest Investigative Site 017
🇺🇸Garden Grove, California, United States
Forest Investigative Site 036
🇺🇸Jupiter, Florida, United States
Forest Investigative Site 020
🇺🇸Colorado Springs, Colorado, United States
Forest Investigative Site 032
🇺🇸Weston, Florida, United States
Forest Investigative Site 016
🇺🇸Sacramento, California, United States
Forest Investigative Site 014
🇺🇸Fountain Valley, California, United States
Forest Investigative Site 027
🇺🇸Gainesville, Florida, United States
Forest Investigative Site 010
🇺🇸Gold River, California, United States
Forest Investigative Site 011
🇺🇸Orange, California, United States
Forest Investigative Site 047
🇺🇸Watertown, Massachusetts, United States
Forest Investigative Site 082
🇺🇸Asheboro, North Carolina, United States
Forest Investigative Site 060
🇺🇸Mentor, Ohio, United States
Forest Investigative Site 022
🇺🇸Oviedo, Florida, United States
Forest Investigative Site 045
🇺🇸Madisonville, Kentucky, United States
Forest Investigative Site 029
🇺🇸Seminole, Florida, United States
Forest Investigative Site 048
🇺🇸Hagerstown, Maryland, United States
Forest Investigative Site 049
🇺🇸Flint, Michigan, United States
Forest Investigative Site 059
🇺🇸Williamsville, New York, United States
Forest Investigative Site 054
🇺🇸Chapel Hill, North Carolina, United States
Forest Investigative Site 053
🇺🇸Winston-Salem, North Carolina, United States
Forest Investigative Site 068
🇺🇸Cumberland, Rhode Island, United States
Forest Investigative Site 079
🇺🇸Bellevue, Washington, United States
Forest Investigative Site 002
🇺🇸Anniston, Alabama, United States
Forest Investigative Site 012
🇺🇸North Hollywood, California, United States
Forest Investigative Site 040
🇺🇸Orlando, Florida, United States
Forest Investigative Site 042
🇺🇸Woodstock, Georgia, United States
Forest Investigative Site 041
🇺🇸Marietta, Georgia, United States
Forest Investigative Site 058
🇺🇸Omaha, Nebraska, United States
Forest Investigative Site 044
🇺🇸Evansville, Indiana, United States
Forest Investigative Site 057
🇺🇸Omaha, Nebraska, United States
Forest Investigative Site 088
🇺🇸Davidson, North Carolina, United States
Forest Investigative Site 051
🇺🇸Flat Rock, North Carolina, United States
Forest Investigative Site 070
🇺🇸Charleston, South Carolina, United States
Forest Investigative Site 078
🇺🇸Christiansburg, Virginia, United States
Forest Investigative Site 084
🇺🇸Ogden, Utah, United States
Forest Investigative Site 076
🇺🇸West Jordan, Utah, United States
Forest Investigative Site 031
🇺🇸Tampa, Florida, United States
Forest Investigative Site 065
🇺🇸Tulsa, Oklahoma, United States
Forest Investigative Site 030
🇺🇸Tampa, Florida, United States
Forest Investigative Site 039
🇺🇸West Palm Beach, Florida, United States
Forest Investigative Site 001
🇺🇸Foley, Alabama, United States
Forest Investigative Site 083
🇺🇸Richardson, Texas, United States
Forest Investigative Site 015
🇺🇸Santa Ana, California, United States
Forest Investigative Site 021
🇺🇸Bristol, Connecticut, United States
Forest Investigative Site 034
🇺🇸Port Orange, Florida, United States
Forest Investigative Site 056
🇺🇸Fargo, North Dakota, United States
Forest Investigative Site 052
🇺🇸Greensboro, North Carolina, United States
Forest Investigative Site 066
🇺🇸Medford, Oregon, United States
Forest Investigative Site 087
🇺🇸Wadsworth, Ohio, United States
Forest Investigative Site 067
🇺🇸Levittown, Pennsylvania, United States
Forest Investigative Site 075
🇺🇸Logan, Utah, United States
Forest Investigative Site 046
🇺🇸Metairie, Louisiana, United States