Long Term Safety of Naldemedine

This is a Phase 3, multi-center, randomized double-blind, placebo controlled, parallel-group
study designed to evaluate the long term safety of naldemedine compared to placebo for the
treatment of opioid-induced constipation (OIC) in subjects with non-malignant chronic pain
receiving opioid therapy.

Inclusion Criteria

1. Subjects aged 18 to 80 years inclusive at the time of informed consent

2. Subjects must have non-malignant chronic pain treated and must have opioid induced
constipation (OIC)

3. Subjects must be treated with a stable opioid regimen at a total daily dose on
average of ≥ 30 mg equivalents of oral morphine sulfate

4. Subjects may or may not be on a routine laxative regimen at the time of Screening

Exclusion Criteria

1. Evidence of significant structural abnormalities of the gastrointestinal (GI) tract

2. Evidence of active medical diseases affecting bowel transit

3. History of pelvic disorders that may be a cause of constipation

4. Surgery (except for minor procedures) within 60 days of Screening

5. 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)

6. Subjects who have never taken laxatives for the treatment of OIC

7. Current use of any prohibited medication including opioid antagonists, partial or
mixed agonists/antagonists