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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Opioid-Induced Constipation

Intervention / Treatment
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* Drug: CB-5945
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CB-5945<br>0.25 milligrams (mg) CB-5945 administered orally twice daily (BID) for a 12-week treatment period | Drug: CB-5945<br> <br> * Other names: ADL5945;|
| Placebo Comparator: Placebo<br>Placebo BID for a 12-week treatment period | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. A Complete SBM (CSBM) Weekly Responder is a participant who has ≥ 3 CSBMs for the specified week and an increase from baseline of ≥1 CSBM for 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Overall Complete Spontaneous Bowel Movement (CSBM) Responder Rates at 12 Weeks | A CSBM Weekly Responder is a participant 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid, Constipation, Chronic, Pain