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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

Primary Purpose

Opioid Induced Constipation

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Placebo
ADL5945 0.1 mg
ADL5945 0.25 mg
Sponsored by
Cubist Pharmaceuticals LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Induced Constipation focused on measuring opioid therapy, constipation, chronic noncancer pain, mu opioid receptor antagonist, ADL5945

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Placebo Comparator

    Experimental

    Experimental

    Arm Label

    Placebo

    ADL5945 0.1 mg

    ADL5945 0.25 mg

    Arm Description

    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).

    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.

    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.

    Outcomes

    Primary Outcome Measures

    Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During 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.

    Secondary Outcome Measures

    Full Information

    First Posted
    September 21, 2010
    Last Updated
    August 27, 2018
    Sponsor
    Cubist Pharmaceuticals LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01207427
    Brief Title
    Evaluation of the Efficacy and Safety of ADL5945 for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    October 14, 2010 (Actual)
    Primary Completion Date
    April 18, 2011 (Actual)
    Study Completion Date
    June 28, 2011 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Cubist Pharmaceuticals LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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, a MOR antagonist, with placebo in the treatment of opioid-induced constipation (OIC) in adults taking long-term opioid therapy for chronic noncancer pain.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Opioid Induced Constipation
    Keywords
    opioid therapy, constipation, chronic noncancer pain, mu opioid receptor antagonist, ADL5945

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    131 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    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).
    Arm Title
    ADL5945 0.1 mg
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    ADL5945 0.25 mg
    Arm Type
    Experimental
    Arm Description
    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.
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Type
    Drug
    Intervention Name(s)
    ADL5945 0.1 mg
    Intervention Type
    Drug
    Intervention Name(s)
    ADL5945 0.25 mg
    Primary Outcome Measure Information:
    Title
    Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment
    Description
    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.
    Time Frame
    Baseline, Weeks 1 through 4 of treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Bruce Berger, MD
    Organizational Affiliation
    Cubist Pharmaceuticals LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php

    Learn more about this trial

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

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