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.
Sponsor:
Information provided by:
Cubist Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01207427
First received: September 21, 2010
Last updated: August 15, 2011
Last verified: August 2011
  Purpose

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 ]

Estimated 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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01207427

Locations
United States, California
Lotus Clinical Research, Inc
Pasadena, California, United States, 91105
Sponsors and Collaborators
Cubist Pharmaceuticals
Investigators
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: August 15, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals:
opioid therapy
constipation
chronic noncancer pain
mu opioid receptor antagonist
ADL5945

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants

ClinicalTrials.gov processed this record on April 21, 2014