The Efficacy and Safety Study of CB-5945 for the Treatment of Opioid-Induced Constipation

This is a multicenter, double-blind, placebo-controlled, parallel-group study in
participants with OIC taking opioid therapy for chronic non-cancer pain. Approximately 600
participants (300 participants per treatment group) with OIC will be randomized at
approximately 75 study centers to receive either oral 0.25 mg CB-5945 BID or oral matching
placebo BID for the 12-week double-blind treatment period, followed by a 4-week follow-up
period. All randomized participants will be evaluated for clinical response for duration of
their study participation. All participants will be followed for safety for 4 weeks after
last dose of the study medication, regardless of when they discontinue study medication. The
clinical study report for this study includes pooled results for studies 5945-OIC-12-02
(NCT01901302) 5945-OIC-12-03 (NCT01901328), and 5945-OIC-12-04 (NCT01901341).

Key Inclusion Criteria:

- Is taking a stable daily dose of opioids of ≥ 30 mg morphine equivalent total daily
dose (METDD) for chronic non-cancer pain

- Has constipation that is caused by the chronic use of opioids

- Is willing to use only the study provided laxative(s) and to discontinue use of all
other laxatives, enemas, stool softeners, and other medications to treat constipation
(e.g., lubiprostone) from Screening until the last study assessment

Key Exclusion Criteria:

- Has gastrointestinal (GI) or pelvic disorders known to affect bowel transit (for
example [e.g.], obstruction) or contribute to bowel dysfunction

- Has evidence of intestinal obstruction

- Has a history of rectal bleeding not due to hemorrhoids or fissures within 6 months
of screening

- Has an active malignancy of any type (participants with a history of successfully
treated malignancy >5 years before the scheduled administration of study medication
and participants with treated basal or squamous cell cancer may be enrolled)

- Is taking antispasmodics (e.g., dicyclomine), antidiarrheals (e.g., loperamide),
prokinetics (e.g., metoclopramide), or locally acting chloride channel activators
(e.g., lubiprostone)

- Is taking non-opioid medications known to cause constipation (e.g., iron sulfate
therapy, tricyclic antidepressants)