NCT01696643

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

Terminated Phase 3 Results posted Last updated 15 November 2018

What this trial tests

Phase 3 trial testing CB-5945 in Opioid-Induced Constipation in 1,407 participants. Terminated before completion.

Timeline

12 October 2012

Primary endpoint
21 July 2014

21 July 2014

Quick facts

Lead sponsor	Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	1,407
Start date	12 October 2012
Primary completion	21 July 2014
Estimated completion	21 July 2014

Drugs / interventions tested

• CB-5945 — full drug profile →
• Placebo

Conditions studied

• Opioid-Induced Constipation — all drugs for Opioid-Induced Constipation →

Sponsor

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) — full company profile →

Who can join

Adults 18 to 80, any sex, with Opioid-Induced Constipation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) Primary · 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 locat

Had at least 1 TEAE

Group	Value	95% CI
CB-5945	58.5
Placebo	54.0

Had at least 1 drug-related TEAE

Group	Value	95% CI
CB-5945	19.9
Placebo	12.1

Discontinued treatment due to a TEAE

Group	Value	95% CI
CB-5945	10.0
Placebo	5.7

Change From Baseline in Mean Daily Opioid Dose at Weeks 49-52 Secondary · 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.

Group	Value	95% CI
CB-5945	-12.456	± 90.2190
Placebo	-12.297	± 88.8681

Change From Baseline in Patient Assessment of Constipation-Quality of Life (PAC-QOL) Questionnaire at Week 52 Secondary · 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

Group	Value	95% CI
CB-5945	-0.63	± 0.699
Placebo	-0.45	± 0.583

Change From Baseline in Patient-Reported Constipation Severity Assessment (PCSA) at Week 52 Secondary · 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.

Group	Value	95% CI
CB-5945	-3.0	± 3.24
Placebo	-2.2	± 3.19

Plasma Trough Concentrations of CB-5945 Secondary · 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.

Week 4 (n=615)

Group	Value	95% CI
CB-5945	517.51	± 403.391

Week 12 (n=522)

Group	Value	95% CI
CB-5945	549.66	± 425.131

Week 24 (n=419)

Group	Value	95% CI
CB-5945	547.31	± 453.548

Week 36 (n=288)

Group	Value	95% CI
CB-5945	573.57	± 517.118

Week 52 (n=203)

Group	Value	95% CI
CB-5945	616.57	± 725.849

Overall (n=631)

Group	Value	95% CI
CB-5945	517.19	± 375.963

Number of Participants With Adjudicated Cardiovascular, Gastrointestinal, or Central Opioid Withdrawal Events Secondary · 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, dyspho

CV event

Group	Value	95% CI
CB-5945	1
Placebo	2

GI event

Group	Value	95% CI
CB-5945	16
Placebo	7

Central OW event

Group	Value	95% CI
CB-5945	7
Placebo	2

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

CB-5945

Serious: 40/703 (6%)

Deaths: —

Placebo

Serious: 36/700 (5%)

Deaths: —

Serious adverse events (78 terms)

Reaction	System	CB-5945	Placebo
Gastroenteritis	Infections and infestations	—	—
Cellulitis	Infections and infestations	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Transient ischaemic attack	Nervous system disorders	—	—
Deep vein thrombosis	Vascular disorders	—	—
Renal failure acute	Renal and urinary disorders	—	—
Clostridium difficile colitis	Infections and infestations	—	—
Empyema	Infections and infestations	—	—
Enteritis infectious	Infections and infestations	—	—
Gastroenteritis viral	Infections and infestations	—	—
Kidney infection	Infections and infestations	—	—
Lobar pneumonia	Infections and infestations	—	—
Localised infection	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Wound infection	Infections and infestations	—	—
Appendicitis	Infections and infestations	—	—
Infected bites	Infections and infestations	—	—
Influenza	Infections and infestations	—	—
Meningitis staphylococcal	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Pyelonephritis	Infections and infestations	—	—

Other adverse events (473 terms — click to expand)

Reaction	System	CB-5945	Placebo
Diarrhoea	Gastrointestinal disorders	—	—
Abdominal Pain	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Back Pain	Musculoskeletal and connective tissue disorders	—	—
Upper Respiratory Tract Infection	Infections and infestations	—	—
Urinary Tract Infection	Infections and infestations	—	—
Headache	Nervous system disorders	—	—
Sinusitis	Infections and infestations	—	—
Abdominal Pain Upper	Gastrointestinal disorders	—	—
Flatulence	Gastrointestinal disorders	—	—
Bronchitis	Infections and infestations	—	—
Nasopharyngitis	Infections and infestations	—	—
Gastroenteritis Viral	Infections and infestations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Hypertension	Vascular disorders	—	—
Influenza	Infections and infestations	—	—
Oedema Peripheral	General disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Muscle Spasms	Musculoskeletal and connective tissue disorders	—	—
Pain In Extremity	Musculoskeletal and connective tissue disorders	—	—
Dizziness	Nervous system disorders	—	—
Drug Withdrawal Syndrome	General disorders	—	—
Anxiety	Psychiatric disorders	—	—
Gastrooesophageal Reflux Disease	Gastrointestinal disorders	—	—
Pain	General disorders	—	—
Insomnia	Psychiatric disorders	—	—
Depression	Psychiatric disorders	—	—
Abdominal Distension	Gastrointestinal disorders	—	—
Gastroenteritis	Infections and infestations	—	—
Tooth Abscess	Infections and infestations	—	—
Neck Pain	Musculoskeletal and connective tissue disorders	—	—
Neuralgia	Nervous system disorders	—	—
Fatigue	General disorders	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—
Hot Flush	Vascular disorders	—	—
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Gastroenteritis, Cellulitis, Osteoarthritis, Rhabdomyolysis, Arthralgia, Back pain, Non-cardiac chest pain, Transient ischaemic attack.

Data from ClinicalTrials.gov NCT01696643 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.