Evaluation of the Efficacy and Safety of ADL5945 for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain

• Status: Completed
• Trial end date: 2011-06-28
• Target enrollment: 0
• Participant gender: All

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, a MOR antagonist, with placebo in the treatment of opioid-induced constipation (OIC) in adults taking long-term opioid therapy for chronic noncancer pain.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cubist Pharmaceuticals LLC
• Treatments: Analgesics, Opioid

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 for pain

• 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