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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01275755
Recruitment Status : Completed
First Posted : January 12, 2011
Results First Posted : June 8, 2015
Last Update Posted : November 15, 2018
Information provided by (Responsible Party):
Cubist Pharmaceuticals LLC

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.

Condition or disease Intervention/treatment Phase
Constipation Drug: Placebo Drug: ADL5945 0.25 mg Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Actual Study Start Date : January 19, 2011
Actual Primary Completion Date : July 15, 2011
Actual Study Completion Date : July 15, 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Constipation

Arm Intervention/treatment
Placebo Comparator: Placebo
Each participant received 1 placebo capsule orally every day (QD) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
Drug: Placebo
Experimental: ADL5945 0.25 mg
During the Run-in Placebo Period, each participant received 1 placebo capsule orally QD for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-milligrams (mg) ADL5945 capsule orally QD for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally QD for 1 week.
Drug: Placebo
Drug: ADL5945 0.25 mg

Primary Outcome Measures :
  1. Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment [ Time Frame: Baseline, Weeks 1 through 4 of treatment ]
    An SBM was defined as a bowel movement (BM) with no laxative use in the previous 24 hours. Each weekly SBM average was calculated as follows: (7 × number of SBMs) / (number of days with nonmissing data). The overall SBM rate for the 4-week double-blind treatment period was calculated as follows: (the average of the first week + the average of the second week + the average of the third week + the average of the fourth week) / 4.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 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
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Responsible Party: Cubist Pharmaceuticals LLC Identifier: NCT01275755    
Other Study ID Numbers: 2402-002
45CL243 ( Other Identifier: Cubist Study Number )
First Posted: January 12, 2011    Key Record Dates
Results First Posted: June 8, 2015
Last Update Posted: November 15, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:
Keywords provided by Cubist Pharmaceuticals LLC:
opioid therapy
chronic noncancer pain
mu opioid receptor antagonist
Opioid Induced Constipation
Additional relevant MeSH terms:
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Signs and Symptoms, Digestive