Clinical trial NCT01207427 (phase 2, status: completed)
Conditions: opioid induced constipation
ICD codes: K59.00, K59.09, K59.01, K59.02, K59.03, K59.04, K58.1
Drugs: placebo, adl5945 0.1 mg, adl5945 0.25 mg
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, COC1=CC(CNCCC2CCOCC2)=CC=C1OC1=CN=C(C=N1)C(N)=O, COC1=CC(CNCCC2CCOCC2)=CC=C1OC1=CN=C(C=N1)C(N)=O
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