Efficacy and Safety of Naldemedine in Treating Opioid-induced Constipation

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Naldemedine in the Treatment of Opioid-induced Constipation in Subjects With Non-malignant Chronic Pain Receiving Opioid Therapy

The purpose of this study is to evaluate the efficacy and safety of naldemedine in the treatment of opioid-induced constipation (OIC) in adults with non-malignant chronic pain who are not using laxatives.

Inclusion Criteria:

• Subjects aged 18 to 80 years inclusive at the time of informed consent
• Subjects must have non-malignant chronic pain treated with opioids and must have opioid-induced constipation (OIC)
• Subjects must be treated with a stable opioid regimen at a total daily dose on average of ≥ 30 mg equivalents of oral morphine sulfate
• Subjects must not be currently using laxatives or must be willing to discontinue laxative use at Screening and must be willing to use only the rescue laxatives provided throughout the study duration
• Subjects must meet opioid-induced constipation criteria based on the Bowel Movement and Constipation Assessment (BMCA) Diary

Exclusion Criteria:

• Evidence of significant structural abnormalities of the gastrointestinal (GI) tract
• Evidence of active medical diseases affecting bowel transit
• History or presence of pelvic disorders that may be a cause of constipation
• Surgery (except for minor procedures) within 60 days of Screening
• History of chronic constipation prior to starting analgesic medication or any potential non-opioid cause of bowel dysfunction that may be a major contributor to the constipation (e.g., mechanical GI obstruction)
• Subjects who have never taken laxatives for the treatment of OIC
• History of active treatment for cancer within the last 2 years (except for basal cell or squamous cell carcinoma of the skin that have been successfully resected) or tamoxifen [Nolvadex®] and raloxifene [Evista®] when being used for prevention of breast cancer
• Current use of any prohibited medication including opioid antagonists, partial agonists, or mixed agonists/antagonists