Study to Evaluate the Safety and Efficacy of Naldemedine (S-297995) for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain

A Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety and Efficacy of S-297995 for the Treatment of Opioid-Induced Bowel Dysfunction in Subjects With Chronic Pain

The primary objective of the study is to evaluate the safety of single doses of oral naldemedine in adults physically dependent on opioids.

A single dose of naldemedine or matching placebo will be administered orally to each cohort of 12 participants (9 treatments, 3 placebos) in the morning of Day 15 under fasted conditions. The first cohort will receive a 0.1 mg dose. Cohorts will continue to be enrolled at the next higher dose level until the highest dose level (3 mg) has been achieved or until the study is discontinued due to adverse events or Clinical Opioid Withdrawal Score of >8. A 0.03 mg dose will also be tested. A 0.01 mg dose will be tested if 4 or more subjects experience 1 or more bowel movements within the 24 hour period post dose in the 0.03 mg dosing cohort.

Inclusion Criteria:

• Understand and sign an informed consent form
• Males will agree to use an approved double-barrier method of contraception from Day 1 until 1 month after study completion
• Subject tests negative on urine drug test unless the subject has a prescription for the drug(s) that test positive

Exclusion Criteria:

• Subjects under opioid therapy for cancer-related pain or for the management of drug addiction
• Fecal incontinence, irritable bowel syndrome, inflammatory bowel disease, or other active medical disorders associated with diarrhea, intermittent loose stools, or constipation
• Subjects who have participated in any other investigational drug study within 30 days prior to Day 1
• Prior exposure to S-297995