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

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