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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Constipation
Keywords: opioid therapy
constipation
chronic noncancer pain
mu opioid receptor antagonist
ADL5945
Opioid Induced Constipation
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2011-01-12
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment
timeFrame: Baseline, Weeks 1 through 4 of treatment
Secondary outcomes:
Other outcomes:
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