Evaluation of the Efficacy and Safety of ADL5945 for the Treatment of Opioid-induced Constipation in Adults Taking Opioid Therapy for Chronic Noncancer Pain

Phase 2

Completed

Conditions: Opioid Induced Constipation

Interventions: Drug: Placebo
Drug: ADL5945 0.1 mg
Drug: ADL5945 0.25 mg

Registration Number: NCT01207427

Lead Sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Brief Summary: Morphine and related opioid analgesics are known to slow gastrointestinal (GI) motility and reduce intestinal secretion through their binding to μ opioid receptors (MORs) within the GI tract. The most common symptoms associated with the effects of opioids are constipation and nausea and/or vomiting. Moreover, constipation is a common and distressing side effect of long-term opioid therapy.

The primary objective of this study was to compare ADL5945, a MOR antagonist, with placebo in the treatment of opioid-induced constipation (OIC) in adults taking long-term opioid therapy for chronic noncancer pain.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 131

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ADL5945 0.1 mg	Placebo	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-milligrams (mg) ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
ADL5945 0.1 mg	ADL5945 0.1 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.1-milligrams (mg) ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
Placebo	Placebo	Each participant received 1 placebo capsule orally twice daily (BID) during the Run-in Placebo Period (1 week), the Double-blind Treatment Period (4 weeks), and the Run-out Placebo Period (1 week).
ADL5945 0.25 mg	Placebo	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.
ADL5945 0.25 mg	ADL5945 0.25 mg	During the Run-in Placebo Period, each participant received 1 placebo capsule orally BID for 1 week. Then during the Double-blind Treatment Period, each participant received one 0.25-mg ADL5945 capsule orally BID for 4 weeks. Then during the Run-out Placebo Period, each participant received 1 placebo capsule orally BID for 1 week.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Weekly Average of Spontaneous Bowel Movements (SBMs) During Treatment	Baseline, Weeks 1 through 4 of treatment	An SBM was defined as a bowel movement (BM) with no laxative use in the previous 24 hours. Each weekly SBM average was calculated as follows: (7 × number of SBMs) / (number of days with nonmissing data). The overall SBM rate for the 4-week double-blind treatment period was calculated as follows: (the average of the first week + the average of the second week + the average of the third week + the average of the fourth week) / 4.

Secondary Outcome Measures