Evaluation of the Efficacy and Safety of ADL5945 for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain
Condition: Opioid Induced Constipation
MeSH terms: Constipation; Opioid-Induced Constipation
Intervention: Placebo; ADL5945 0.1 mg; ADL5945 0.25 mg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: opioid therapy; constipation; chronic noncancer pain; mu opioid receptor antagonist; ADL5945

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.
    

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