Symptoms and General Pathology

All Conditions

Substance Related Disorders

Behaviors and Mental Disorders

Rare Diseases

Constipation

Pain

Opioid-Induced Constipation

Signs and Symptoms, Digestive

Narcotic-Related Disorders

Substance-Related Disorders

Chemically-Induced Disorders

Mental Disorders

Psychotic Disorders

Chronic Graft Versus Host Disease

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Analgesics, Opioid

0.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks

Placebo, administered orally, BID for 52 weeks

CB-5945

Placebo

Medical Monitor

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.

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.

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

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

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Cardiovascular (CV) events of interested included mycardial infarction, unstable angina, CV accident, congestive heart failure, serious arrhythmia, resuscitated cardiac arrest, and death.

Gastrointestinal (GI) events of interest included emergency department visits for the serious adverse events of gastroenteritis, hepatitis, pancreatitis, nausea, vomiting, diarrhea, and abdominal pain or cramping.

Central opioid withdrawal (OW) events of interest included opioid withdrawal syndrome. The adverse events that indicated central OW included, but were not limited to, hyperhidrosis, tremor, dysphoria, and myalgia.

The number of participants with at least 1 confirmed CV, GI, or Central OW event is presented.

A TEAE was defined as any adverse event (AE) that occurred from the time of first dose of the study drug through the last study evaluation or pre-existing AEs that were aggravated in severity or frequency during the dosing period. The percentages of participants with at least 1 TEAE, with at least 1 drug-related TEAE (drug-related included "possibly related" or "related" as deemed by the Investigator; it also included events if causality was missing), and who discontinued from treatment due to a TEAE are presented. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Throughout the study, participants were asked to record changes in maintenance opioid consumption and use of opioid analgesics for breakthrough or exacerbation of pain in a paper diary. Opioid consumption (including rescue opioids) of each participant was converted to an oral morphine-equivalent total daily dose (METDD). Opioid consumption (in milligrams of METDD) was summarized in 4-week intervals. The change from baseline to Weeks 49-52 is summarized.

The PAC-QOL questionnaire contains a total of 28 items, each rated within 4 subscales: physical discomfort, psychosocial discomfort, worries and concerns, and satisfaction. Each item was rated on a 5-point Likert scale with the following score definitions, depending on the question: 0 = not at all (or none of the time), 1 = a little bit (or a little of the time), 2 = moderately (or some of the time), 3 = quite a bit (or most of the time), and 4 = extremely (or all of the time). The total score is the mean of all non-missing items. The range of the total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). Negative change from baseline values indicate improvement in constipation quality of life. Each participant completed the PAC-QOL at Baseline and Week 52 using a 2-week recall period.

The PCSA asked participants to rate the severity of their overall constipation during the 24 hours prior to the assessment, using a scale of 0 to 10, where 0 is no constipation and 10 is the worst constipation imaginable.

Blood samples for trough concentrations of CB-5945 were collected before the participant's morning dose of study drug at Weeks 4, 12, 24, 36, and 52. Overall concentration was based on the mean trough level for each participant across all weeks.

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

Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.

0.25 mg CB-5945, administered orally, BID for 52 weeks

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Region of Enrollment

All randomized participants who received at least 1 dose of study drug. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.

Vice President, Clinical Research

Had at least 1 TEAE

Had at least 1 drug-related TEAE

Discontinued treatment due to a TEAE

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

All randomized participants who received at least 1 dose of study drug and had evaluable METDD data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.

Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52

All randomized participants who received at least 1 dose of study drug and had evaluable PAC-QOL data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.

Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52

All randomized participants who received at least 1 dose of study drug and had evaluable PCSA data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.

Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52

Week 4 (n=615)

Week 12 (n=522)

Week 24 (n=419)

Week 36 (n=288)

Week 52 (n=203)

Overall (n=631)

All participants randomized to CB-5945 who received at least 1 dose of study drug and had evaluable CB-5945 concentration data. Two participants were randomized to the Placebo Arm but were administered CB-5945 instead. As a result, these 2 participants were included in the CB-5945 Arm for analysis.

Spots Global Cancer Trial Database for Safety Study of CB-5945 for the Treatment of Opioid-Induced Constipation

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial