Trial Outcomes & Findings for Efficacy and Safety Study of CB-5945 for the Treatment of Opioid-Induced Constipation (NCT NCT01901328)

NCT ID: NCT01901328

Last Updated: 2018-11-15

Results Overview

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).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

49 participants

Primary outcome timeframe

12 weeks

Results posted on

2018-11-15

Participant Flow

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

Participant milestones

Participant milestones
Measure	CB-5945 0.25 milligrams (mg) CB-5945 administered orally twice dailly (BID) for a 12-week treatment period	Placebo Placebo administered orally BID for a 12-week treatment period
Overall Study STARTED	26	23
Overall Study Received at Least 1 Dose of Study Drug	26	23
Overall Study COMPLETED	4	2
Overall Study NOT COMPLETED	22	21

Reasons for withdrawal

Reasons for withdrawal
Measure	CB-5945 0.25 milligrams (mg) CB-5945 administered orally twice dailly (BID) for a 12-week treatment period	Placebo Placebo administered orally BID for a 12-week treatment period
Overall Study Lost to Follow-up	1	0
Overall Study Physician Decision	0	1
Overall Study Protocol Violation	1	1
Overall Study Study Terminated by Sponsor	19	16
Overall Study Withdrawal by Subject	1	2
Overall Study Lack of Efficacy	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CB-5945 n=26 Participants 0.25 mg CB-5945 administered orally BID for a 12-week treatment period	Placebo n=23 Participants Placebo administered orally BID for a 12-week treatment period	Total n=49 Participants Total of all reporting groups
Age, Categorical LTE18	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical BTWN	25 Participants n=99 Participants	22 Participants n=107 Participants	47 Participants n=206 Participants
Age, Categorical GTE65	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Sex: Female, Male Female	19 Participants n=99 Participants	18 Participants n=107 Participants	37 Participants n=206 Participants
Sex: Female, Male Male	7 Participants n=99 Participants	5 Participants n=107 Participants	12 Participants n=206 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: Zero participants were analyzed, and no data was collected for this measure. Due to lack of enrollment, the study was terminated early.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Zero participants were analyzed, and no data was collected for this measure. Due to lack of enrollment, the study was terminated early.

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").

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 weeks

Population: Zero participants were analyzed, and no data was collected for this measure. Due to lack of enrollment, the study was terminated early.

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).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline through 16 weeks

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.

Outcome measures

Outcome measures
Measure	CB-5945 n=26 Participants 0.25 mg CB-5945 administered orally BID for a 12-week treatment period	Placebo n=23 Participants Placebo administered orally BID for a 12-week treatment period
Adjudicated Cardiovascular, Gastrointestinal and Central Opioid Withdrawal Events Subjects with at Least One Confirmed CV Event	0 participants	0 participants
Adjudicated Cardiovascular, Gastrointestinal and Central Opioid Withdrawal Events Subjects with at Least One Confirmed GI Event	0 participants	0 participants
Adjudicated Cardiovascular, Gastrointestinal and Central Opioid Withdrawal Events Subjects with at Least One Confirmed OW Event	0 participants	0 participants

Adverse Events

CB-5945

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Vice President, Clinical Research

Cubist Pharmaceuticals

Phone: (781) 860-8660

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	CB-5945 n=26 participants at risk 0.25 mg CB-5945 administered orally BID for a 12-week treatment period	Placebo n=23 participants at risk Placebo administered orally BID for a 12-week treatment period
Gastrointestinal disorders Abdominal pain	11.5% 3/26 • Number of events 3 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Gastrointestinal disorders Diarrhoea	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Gastrointestinal disorders Gastrooesophageal reflux disease	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Gastrointestinal disorders Nausea	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
General disorders Drug withdrawal syndrome	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Infections and infestations Acute sinusitis	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Infections and infestations Bronchitis	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Infections and infestations Nasopharyngitis	0.00% 0/26 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Infections and infestations Oral candidiasis	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Infections and infestations Upper respiratory tract infection	0.00% 0/26 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Infections and infestations Urinary tract infection	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 2 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/26 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Musculoskeletal and connective tissue disorders Back pain	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/26 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Musculoskeletal and connective tissue disorders Pain in extremity	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Nervous system disorders Headache	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Nervous system disorders Sensory loss	3.8% 1/26 • Number of events 2 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	0.00% 0/23 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
General disorders Fall	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Injury, poisoning and procedural complications Flatulence	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.
Infections and infestations Rash erythematous	3.8% 1/26 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.	4.3% 1/23 • Number of events 1 • Baseline through 16 weeks SAEs that occurred before the first dose of double-blind study medication were only included in the safety database.