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

Primary Purpose

Opioid-Induced Constipation

Status

Terminated

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

CB-5945

Placebo

About this trial

This is an interventional treatment trial for Opioid-Induced Constipation focused on measuring Opioid, Constipation, Chronic, Pain

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CB-5945

Placebo

Arm Description

0.25 milligrams (mg) CB-5945 administered orally twice daily (BID) for a 12-week treatment period

Placebo administered orally BID for a 12-week treatment period

Outcomes

Primary Outcome Measures

Overall Spontaneous Bowel Movement (SBM) Responder Rates at the 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).

Secondary Outcome Measures

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").

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).

Full Information

NCT ID

NCT01901341

First Posted

July 9, 2013

Last Updated

October 17, 2018

Sponsor

Cubist Pharmaceuticals LLC

1. Study Identification

Unique Protocol Identification Number

NCT01901341

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Terminated

Why Stopped

Due to difficulties with enrollment, the study was terminated early.

Study Start Date

July 2, 2013 (Actual)

Primary Completion Date

February 13, 2014 (Actual)

Study Completion Date

February 13, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cubist Pharmaceuticals LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

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 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Opioid-Induced Constipation

Keywords

Opioid, Constipation, Chronic, Pain

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CB-5945

Arm Type

Experimental

Arm Description

0.25 milligrams (mg) CB-5945 administered orally twice daily (BID) for a 12-week treatment period

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo administered orally BID for a 12-week treatment period

Intervention Type

Drug

Intervention Name(s)

CB-5945

Other Intervention Name(s)

Bevenopran, ADL5945

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Overall Spontaneous Bowel Movement (SBM) Responder Rates at the 12-weeks

Description

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Change From Baseline of Chronic Opioid-Related Gastrointestinal Symptom Scale (CORGISS) Scores at 12 Weeks

Description

Time Frame

Baseline, 12 weeks

Title

Overall Complete Spontaneous Bowel Movement (CSBM) Responder Rates at 12 Weeks

Description

Time Frame

12 weeks

Other Pre-specified Outcome Measures:

Title

Cardiovascular, Gastrointestinal and Central Opioid Withdrawal Events

Description

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.

Time Frame

Baseline through 16 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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)

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Learn more about this trial

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

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