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 - Full Text View

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 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.

Condition	Intervention	Phase
Constipation	Drug: Placebo 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 Once Daily for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain

Resource links provided by NLM:

MedlinePlus related topics: Constipation

U.S. FDA Resources

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:	80
Study Start Date:	January 2011
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 once daily
Experimental: ADL5945 0.25 mg	Drug: ADL5945 0.25 mg 0.25 mg once 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
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: NCT01275755

Locations

United States, Florida
Compass Research, LLC
Orlando, Florida, United States, 32806
United States, Louisiana
Louisiana Research Associates Inc
New Orleans, Louisiana, United States, 70114

Sponsors and Collaborators

Cubist Pharmaceuticals

More Information

No publications provided

Responsible Party:	Bruce Berger, Senior Medical Director, Adolor
ClinicalTrials.gov Identifier:	NCT01275755 History of Changes
Other Study ID Numbers:	45CL243
Study First Received:	January 11, 2011
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
Opioid Induced Constipation

Additional relevant MeSH terms:

Constipation
Signs and Symptoms, Digestive
Signs and Symptoms
Narcotic Antagonists
Analgesics, Opioid
Physiological Effects of Drugs
Pharmacologic Actions

Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Analgesics
Central Nervous System Depressants

ClinicalTrials.gov processed this record on May 16, 2013