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

Conditions: Constipation

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.


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 * 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

Keywords: opioid therapy constipation chronic noncancer pain mu opioid receptor antagonist adl5945 opioid induced constipation