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

Opioid-Induced Constipation Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of CB-5945 for the Treatment of Opioid-Induced Constipation in Adults Taking Opioid Therapy for Chronic Non-Cancer Pain

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01901328
• Other study ID #: 2402-004
• Secondary ID: 5945-OIC-12-03
• Status: Terminated
• Phase: Phase 3
• Start date: April 7, 2013
• Est. completion date: February 13, 2014

Study information

• Verified date: October 2018
• Source: Cubist Pharmaceuticals LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 49
• Est. completion date: February 13, 2014
• Est. primary completion date: February 13, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Constipation
• Opioid-Induced Constipation

Intervention

Drug:
• CB-5945

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Cubist Pharmaceuticals LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adjudicated Cardiovascular, Gastrointestinal and Central Opioid Withdrawal Events	Cardiovascular (CV) events of interested included myocardial infarction, unstable angina, cardiovascular accident, congestive heart failure, serious arrhythmia, resuscitated cardiac arrest, and death.; Gastrointestinal (GI) events of interest included emergency department visits for SAEs of gastroenteritis, hepatitis, pancreatitis, nausea, vomiting, diarrhea, and abdominal pain or cramping.; Central opioid withdrawal events of interest included opioid withdrawal syndrome.	Baseline through 16 weeks
Primary	Overall Spontaneous Bowel Movement (SBM) Responder Rates at 12-weeks	A Spontaneous Bowel Movement (SBM) Weekly Responder (calculated for each week of the 12-week double-blind treatment period) is a participant who has = 3 SBMs for the week and an increase from baseline of =1 SBM for the specified week, based on at least 4 Available Data Days (ADDs) during the week. For the definition of the primary efficacy endpoint, Overall SBM Responder is a participant who is a Weekly SBM Responder for 9 of the 12 weeks of the double-blind treatment period, including 3 of the last 4 weeks (Weeks 9, 10, 11 and 12).	12 weeks
Secondary	Change From Baseline of Chronic Opioid-Related Gastrointestinal Symptom Scale (CORGISS) Scores at 12 Weeks	The CORGISS is designed to assess GI symptoms related to opioid use in patients with chronic non-cancer pain. The CORGISS asks participants to rate the severity of GI symptoms over the previous 24 hours, with answers ranging from 0 ("did not experience") to 4 ("very severe").	Baseline, 12 weeks
Secondary	Overall Complete Spontaneous Bowel Movement (CSBM) Responder Rates at 12 Weeks	A CSBM Weekly Responder is a subject who has = 3 CSBMs for the specified week and an increase from baseline of =1 CSBM for the week. An Overall CSBM Responder is a subject who is a Weekly CSBM Responder for 9 of the 12 weeks of the double-blind treatment period, including 3 of the last 4 weeks (Weeks 9, 10, 11 and 12).	12 weeks