Clinical trial NCT01696643: Safety Study of CB-5945 for the Treatment of Opioid-Induced Constipation
Official title: Phase 3 Study to Evaluate the Long-Term Safety and Tolerability of CB-5945 for the Treatment of Opioid-Induced Constipation in Adults Taking Opioid Therapy for Chronic Non-Cancer Pain
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Opioid-Induced Constipation
Keywords: Opioid
Constipation
Chronic
Pain
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2012-10-01
Enrollment: 1407
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the long-term safety and tolerability of CB-5945 for the treatment of opioid-induced constipation (OIC) in adults taking opioid therapy for chronic non-cancer pain.

Detailed description: This is a multicenter, double-blind, placebo-controlled, parallel-group study in participants with OIC taking opioid therapy for chronic non-cancer pain. Approximately 1,400 participants (approximately 700 participants per treatment group) with OIC will be randomized at approximately 225 study centers to receive either 0.25 milligrams (mg) CB-5945 twice daily (BID) or a matching placebo BID for the 52-week double-blind treatment period, followed by a 4-week follow-up period. All randomized participants will be evaluated for safety, tolerability, and quality of life from the first dose of study drug through Week 56.

Eligibility criteria: 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 (for example, lubiprostone) during the study period (from Screening until the last study assessment).
* Is able and willing to refrain from facilitating defecation via manual maneuvers (for example, digital evacuation or support of the pelvic floor) during the study period (from Screening to the last study assessment)

Exclusion Criteria:

* Has gastrointestinal (GI) or pelvic disorders known to affect bowel transit (for example, obstruction) or contribute to bowel dysfunction
* Has evidence of intestinal obstruction
* Has a history of rectal bleeding not due to hemorrhoids or fissures
* 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 (for example, dicyclomine), antidiarrheals (for example, loperamide), prokinetics (for example, metoclopramide), or locally acting chloride channel activators (for example, lubiprostone)
* Is taking non-opioid medications known to cause constipation (for example, iron sulfate therapy or tricyclic antidepressants)

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline through Week 56
Secondary outcomes:
measure: Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52
timeFrame: Baseline, Weeks 49-52
measure: Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52
timeFrame: Baseline, Week 52
measure: Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52
timeFrame: Baseline, Week 52
measure: Plasma Trough Concentrations of CB-5945
timeFrame: Weeks 4, 12, 24, 36, and 52
Other outcomes:
measure: Number of Participants With Adjudicated Cardiovascular, Gastrointestinal, or Central Opioid Withdrawal Events
timeFrame: Baseline through Week 56
Locations:
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Medical Monitor
role: STUDY_DIRECTOR
References: