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

This study has been completed.
Information provided by:
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
First received: September 21, 2010
Last updated: March 5, 2015
Last verified: March 2015

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.

Condition Intervention Phase
Opioid Induced Constipation
Drug: Placebo
Drug: ADL5945 0.1 mg
Drug: ADL5945 0.25 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of ADL5945 for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain

Resource links provided by NLM:

Further study details as provided by Cubist Pharmaceuticals:

Primary Outcome Measures:
  • Change from baseline in the weekly average of spontaneous bowel movements (SBMs) during treatment [ Time Frame: Weeks 1 through 4 of treatment ] [ Designated as safety issue: No ]

Enrollment: 120
Study Start Date: October 2010
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
twice daily
Experimental: ADL5945 0.1 mg Drug: ADL5945 0.1 mg
twice daily
Experimental: ADL5945 0.25 mg Drug: ADL5945 0.25 mg
twice daily


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Key Inclusion Criteria

  • be a man or woman aged 18 to 75 years, inclusive, at the time of screening
  • have a body weight ≥ 45 kg and a body mass index (BMI) ≤ 40 kg/m2
  • be taking a stable daily dose of opioids of ≥ 30-mg morphine-equivalent total daily dose for chronic noncancer pain for ≥ 30 days before screening
  • have OIC by history and based on the data collected during the 1-week screening period: subjects must have < 3 SBMs per week and have experienced ≥ 1 other BM symptom (ie, 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 (subjects 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 MOR antagonist, including opioids in combination with naloxone, naltrexone, or methylnaltrexone bromide
  • be taking medical marijuana for pain
  • have 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, 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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01207427

United States, California
Lotus Clinical Research, Inc
Pasadena, California, United States, 91105
Sponsors and Collaborators
Cubist Pharmaceuticals
Study Director: Bruce Berger, MD Cubist Pharmaceuticals
  More Information

No publications provided

Responsible Party: Bruce Berger, Senior Medical Director, Adolor Corporation
ClinicalTrials.gov Identifier: NCT01207427     History of Changes
Other Study ID Numbers: 45CL242
Study First Received: September 21, 2010
Last Updated: March 5, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals:
opioid therapy
chronic noncancer pain
mu opioid receptor antagonist

Additional relevant MeSH terms:
Signs and Symptoms
Signs and Symptoms, Digestive

ClinicalTrials.gov processed this record on April 23, 2015