Opioid-Induced ConstipationPhase 3NCT01696643
Safety Study of CB-5945 for the Treatment of Opioid-Induced Constipation
A Phase 3 study testing CB-5945 in people with Opioid-Induced Constipation, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Opioid-Induced Constipation
- What is being tested?
- CB-5945
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,407 participants
- Where
- No sites listed yet
- Study dates
- 12 Oct 2012to 21 Jul 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
About this study
Official title: 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.
Read the 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.
- Conditions
- Opioid-Induced Constipation
- Being tested
- CB-5945, Placebo
- Keywords
- Opioid, Constipation, Chronic, Pain
- Medical subject headings
- Opioid-Induced Constipation, Constipation, Bronchiolitis Obliterans Syndrome, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CB-5945Drug
Also called Bevenopran
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| CB-5945 | Experimental | 0.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks Receives: Drug: CB-5945 |
| Placebo | Placebo comparator | Placebo, administered orally, BID for 52 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Measured: Baseline through Week 56
Secondary outcomes (4)
Change From Baseline in Mean Daily Opioid Dose at 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.
Measured: Baseline, Weeks 49-52
Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at 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.
Measured: Baseline, Week 52
Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at 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.
Measured: Baseline, Week 52
Plasma Trough Concentrations of CB-5945
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.
Measured: Weeks 4, 12, 24, 36, and 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2012 (estimated)
- Study start12 Oct 2012
- Primary completion21 Jul 2014
- Study completion21 Jul 2014
Why it stopped: A review of blinded data indicates that the number of participant exposures needed to reach ICH standards has been met
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Opioid-Induced ConstipationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 1,407 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01696643
- Sponsor's protocol ID
- 2402-006
- Other IDs
- 5945-SOIC-12-05
- Status last verified
- Oct 2018
- First submitted
- 21 Sep 2012
- Last updated
- 15 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01696643
- Acronym / sponsor ID
- 2402-006
- Conditions
- Opioid-Induced Constipation
- Keywords
- Opioid, Constipation, Chronic, Pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A review of blinded data indicates that the number of participant exposures needed to reach ICH standards has been met
- Enrolment
- 1,407 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- 12 Oct 2012 (actual)
- Primary completion
- 21 Jul 2014 (actual)
- Study completion
- 21 Jul 2014 (actual)
- First posted
- 1 Oct 2012 (estimated)
- Results
- Posted 28 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CB-5945 | Experimental | Drug: CB-59450.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, administered orally, BID for 52 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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)
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CB-5945Also: Bevenopran | Drug | CB-5945 |
| Placebo | Drug | Placebo |
Primary outcome
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.
4 secondary outcomes
Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52
Time frame: 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
Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52
Time frame: Baseline, Week 52
Plasma Trough Concentrations of CB-5945
Time frame: Weeks 4, 12, 24, 36, and 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CB-5945 in people with Opioid-Induced Constipation, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: Baseline through Week 56). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2018.