- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01275755
Evaluation of the Efficacy and Safety of ADL5945 Once Daily for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain
A Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of ADL5945 Once Daily for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain
Morphine and related opioid analgesics are known to slow gastrointestinal (GI) motility and reduce intestinal secretion through their binding to μ opioid receptors (MORs) within the GI tract. The most common symptoms associated with the effects of opioids are constipation and nausea and/or vomiting. Moreover, constipation is a common and distressing side effect of long-term opioid therapy.
The primary objective of this study was to compare ADL5945 once daily, a MOR antagonist, with placebo in the treatment of opioid-induced constipation (OIC) in adults taking long-term opioid therapy for chronic noncancer pain.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Key Inclusion Criteria
- be a man or woman aged 18 to 75 years, inclusive, at the time of screening
- have a body weight ≥45 kilograms (kg) and a body mass index (BMI) ≤40 kilograms per square meter (kg/m^2)
- be taking a stable daily dose of opioids of ≥30-milligrams (mg) morphine-equivalent total -daily dose for chronic noncancer pain for ≥30 days before screening
- have opioid-induced constipation (OIC) by history. Additionally, based on the data collected during the 1-week screening period, participants must have <3 spontaneous bowel movements (SBMs) per week and have experienced ≥1 other bowel movement (BM) symptom (that is, straining to pass a stool, lumpy hard stools or small pellets, or sense of incomplete evacuation after passing a stool) for ≥25% of the total BMs
- be willing to discontinue use of all laxatives and stool softeners during the study period except as allowed by the protocol
Key Exclusion Criteria
- be pregnant, lactating, or planning to become pregnant during the study
- have aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen, or serum creatinine results ≥2 times the upper limit of normal
- have a recent history of myocardial infarction (MI) or unstable angina
- have an active malignancy of any type
- be taking opioids primarily for fibromyalgia
- be taking methadone as a maintenance medication (participants taking methadone for pain may be enrolled)
- be taking intrathecal opioids for the management of pain
- be taking tramadol, tapentadol, or any mixed agonist/antagonist opioid analgesics as the sole opioid for analgesia
- be taking any μ-opioid receptors (MOR) antagonist, including opioids in combination with naloxone, naltrexone, or methylnaltrexone bromide
- be taking medical marijuana
- have gastrointestinal (GI) or pelvic disorders known to affect bowel transit, produce GI obstruction, or contribute to bowel dysfunction
- have taken antispasmodics, antidiarrheals, or prokinetics within 7 days before the start of the screening week
- be taking nonopioid medications known to cause constipation
- be taking antidiarrheals and have an incidence or a history of intermittent diarrhea or loose stools
- be unwilling to abstain from grapefruit and grapefruit-containing products
- have a history of alcoholism or illicit drug dependence or abuse within 5 years before screening
- have positive results on a urine drug screen (excluding opioids) that indicate illicit drug use
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Each participant received 1 placebo capsule orally every day (QD) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
|
|
Experimental: ADL5945 0.25 mg
During the Run-in Placebo Period, each participant received 1 placebo capsule orally QD for 1 week.
Then during the Double-blind Treatment Period, each participant received one 0.25-milligrams (mg) ADL5945 capsule orally QD for 4 weeks.
Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally QD for 1 week.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment
Time Frame: Baseline, Weeks 1 through 4 of treatment
|
An SBM was defined as a bowel movement (BM) with no laxative use in the previous 24 hours.
Each weekly SBM average was calculated as follows: (7 × number of SBMs) / (number of days with nonmissing data).
The overall SBM rate for the 4-week double-blind treatment period was calculated as follows: (the average of the first week + the average of the second week + the average of the third week + the average of the fourth week) / 4.
|
Baseline, Weeks 1 through 4 of treatment
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2402-002
- 45CL243 (Other Identifier: Cubist Study Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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