A Phase 3 interventional study of CB-5945 and Placebo in Opioid-Induced Constipation, sponsored by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA). Terminated. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2018-11-15.
Sponsored by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) · Phase 3, Interventional, and Treatment
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.
1,018 studies on the registry are indexed under Constipation; 139 are open to participants now.
This study's enrollment of 1,407 is above the median of 80 across 850 interventional studies indexed under Constipation.
Browse Constipation studies →Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) is the lead sponsor of 65 studies on the registry; none are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 5 (83%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
0.25 milligrams (mg) CB-5945, administered orally, twice daily (BID) for 52 weeks
Drug: CB-5945
Placebo, administered orally, BID for 52 weeks
Drug: Placebo
Also known as: Bevenopran
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.
Time frame: Baseline through Week 56
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Weeks 4, 12, 24, 36, and 52
Number of Participants With Adjudicated Cardiovascular, Gastrointestinal, or Central Opioid Withdrawal Events
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.
Time frame: Baseline through Week 56
| Milestone | CB-5945 | Placebo |
|---|---|---|
| Started | 703 | 704 |
| Received at least 1 dose of study drug | 701 | 702 |
| Completed | 174 | 169 |
| Not completed | 529 | 535 |
| Withdrew: Adverse event | 15 | 7 |
| Withdrew: Death | 1 | 2 |
| Withdrew: Lack of efficacy | 3 | 0 |
| Withdrew: Lost to follow-up | 67 | 67 |
| Withdrew: Physician decision | 3 | 2 |
| Withdrew: Pregnancy | 0 | 1 |
| Withdrew: Protocol violation | 7 | 7 |
| Withdrew: Study terminated by sponsor | 286 | 294 |
| Withdrew: Withdrawal by subject | 142 | 149 |
| Withdrew: Participant on restricted bed rest | 1 | 0 |
| Withdrew: Site error | 2 | 1 |
| Withdrew: Participant incarcerated | 0 | 1 |
| Withdrew: Medical monitor decision | 0 | 2 |
| Withdrew: Participant did not receive study drug | 2 | 2 |
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.
| percentage of participants | CB-5945 | Placebo |
|---|---|---|
| Had at least 1 TEAE | 58.5 | 54.0 |
| Had at least 1 drug-related TEAE | 19.9 | 12.1 |
| Discontinued treatment due to a TEAE | 10.0 | 5.7 |
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.
| milligrams of METDD | CB-5945 | Placebo |
|---|---|---|
| Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52 | -12.456 ± 90.2190 | -12.297 ± 88.8681 |
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.
| units on a scale | CB-5945 | Placebo |
|---|---|---|
| Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52 | -0.63 ± 0.699 | -0.45 ± 0.583 |
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.
| units on a scale | CB-5945 | Placebo |
|---|---|---|
| Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52 | -3.0 ± 3.24 | -2.2 ± 3.19 |
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.
| picograms per milliliter (pg/mL) | CB-5945 |
|---|---|
| Week 4 (n=615) | 517.51 ± 403.391 |
| Week 12 (n=522) | 549.66 ± 425.131 |
| Week 24 (n=419) | 547.31 ± 453.548 |
| Week 36 (n=288) | 573.57 ± 517.118 |
| Week 52 (n=203) | 616.57 ± 725.849 |
| Overall (n=631) | 517.19 ± 375.963 |
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.
| participants | CB-5945 | Placebo |
|---|---|---|
| CV event | 1 | 2 |
| GI event | 16 | 7 |
| Central OW event | 7 | 2 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| CB-5945 | — | 40/703 (5.7%) | 403/703 (57.3%) |
| Placebo | — | 36/700 (5.1%) | 373/700 (53.3%) |
| Event | CB-5945 | Placebo |
|---|---|---|
| CellulitisInfections and infestations | 1/703 | 3/700 |
| GastroenteritisInfections and infestations | 3/703 | 0/700 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/703 | 2/700 |
| Back painMusculoskeletal and connective tissue disorders | 0/703 | 2/700 |
| Non-cardiac chest painGeneral disorders | 2/703 | 2/700 |
| Transient ischaemic attackNervous system disorders | 0/703 | 2/700 |
| Renal failure acuteRenal and urinary disorders | 0/703 | 2/700 |
| OsteoarthritisMusculoskeletal and connective tissue disorders | 2/703 | 1/700 |
| RhabdomyolysisMusculoskeletal and connective tissue disorders | 2/703 | 1/700 |
| Deep vein thrombosisVascular disorders | 2/703 | 0/700 |
| Event | CB-5945 | Placebo |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 90/703 | 33/700 |
| Abdominal PainGastrointestinal disorders | 57/703 | 32/700 |
| NauseaGastrointestinal disorders | 51/703 | 39/700 |
| VomitingGastrointestinal disorders | 35/703 | 20/700 |
| Back PainMusculoskeletal and connective tissue disorders | 31/703 | 17/700 |
| Upper Respiratory Tract InfectionInfections and infestations | 18/703 | 28/700 |
| Urinary Tract InfectionInfections and infestations | 25/703 | 22/700 |
| HeadacheNervous system disorders | 20/703 | 23/700 |
| SinusitisInfections and infestations | 17/703 | 22/700 |
| Abdominal Pain UpperGastrointestinal disorders | 20/703 | 11/700 |
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.
| Age, Continuous(years) | CB-5945 | Placebo | Total |
|---|---|---|---|
| Mean | 54.5 ± 10.00 | 53.9 ± 10.21 | 54.2 ± 10.11 |
| Sex: Female, Male(Participants) | CB-5945 | Placebo | Total |
|---|---|---|---|
| Female | 437 | 417 | 854 |
| Male | 266 | 283 | 549 |
| Ethnicity (NIH/OMB)(Participants) | CB-5945 | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 19 | 41 | 60 |
| Not Hispanic or Latino | 676 | 649 | 1325 |
| Unknown or Not Reported | 8 | 10 | 18 |
| Race (NIH/OMB)(Participants) | CB-5945 | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 7 | 4 | 11 |
| Asian | 11 | 11 | 22 |
| Native Hawaiian or Other Pacific Islander | 2 | 1 | 3 |
| Black or African American | 117 | 122 | 239 |
| White | 563 | 555 | 1118 |
| More than one race | 3 | 6 | 9 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Region of Enrollment(participants) | CB-5945 | Placebo | Total |
|---|---|---|---|
| Canada | 26 | 28 | 54 |
| United States | 677 | 672 | 1349 |
No study locations are listed for this record.
Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)