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 (Responsible Party):
Cubist Pharmaceuticals Holdings LLC ( Cubist Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01207427
First received: September 21, 2010
Last updated: April 21, 2015
Last verified: April 2015

September 21, 2010
April 21, 2015
October 2010
August 2011   (final data collection date for primary outcome measure)
Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment [ Time Frame: Baseline, Weeks 1 through 4 of treatment ] [ Designated as safety issue: No ]
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.
Change from baseline in the weekly average of spontaneous bowel movements (SBMs) during treatment [ Time Frame: Weeks 1 through 5 of treatment ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01207427 on ClinicalTrials.gov Archive Site
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Evaluation of the Efficacy and Safety of ADL5945 for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Opioid Induced Constipation
  • Drug: Placebo
  • Drug: ADL5945 0.1 mg
  • Drug: ADL5945 0.25 mg
  • Placebo Comparator: Placebo
    Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
    Intervention: Drug: Placebo
  • Experimental: ADL5945 0.1 mg
    During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-milligrams (mg) ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
    Interventions:
    • Drug: Placebo
    • Drug: ADL5945 0.1 mg
  • Experimental: ADL5945 0.25 mg
    During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
    Interventions:
    • Drug: Placebo
    • Drug: ADL5945 0.25 mg
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
131
August 2011
August 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01207427
45CL242
No
Cubist Pharmaceuticals Holdings LLC ( Cubist Pharmaceuticals )
Cubist Pharmaceuticals
Not Provided
Study Director: Bruce Berger, MD Cubist Pharmaceuticals Holdings LLC
Cubist Pharmaceuticals Holdings LLC
April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP