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

October 17, 2018 updated by: Cubist Pharmaceuticals LLC

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1407

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CB-5945
0.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks
Drug: CB-5945
Other Names:
  • Bevenopran
Placebo Comparator: Placebo
Placebo, administered orally, BID for 52 weeks
Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Baseline through Week 56
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.
Baseline through Week 56

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52
Time Frame: Baseline, Weeks 49-52
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.
Baseline, Weeks 49-52
Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52
Time Frame: Baseline, Week 52
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.
Baseline, Week 52
Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52
Time Frame: Baseline, Week 52
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.
Baseline, Week 52
Plasma Trough Concentrations of CB-5945
Time Frame: Weeks 4, 12, 24, 36, and 52
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.
Weeks 4, 12, 24, 36, and 52

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adjudicated Cardiovascular, Gastrointestinal, or Central Opioid Withdrawal Events
Time Frame: Baseline through Week 56

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.
Baseline through Week 56

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cubist Pharmaceuticals LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 12, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 21, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 21, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 26, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 1, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 15, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2402-006
  • 5945-SOIC-12-05 (Other Identifier: Cubist Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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