Trial Outcomes & Findings for Phase 2 RCT of Alvimopan vs. Placebo After CRS/HIPEC (NCT NCT03352414)

Results Overview

The later of the time from surgery that the participant first tolerates solid food and the time that the participant first passes a bowel movement.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

84 participants

Primary outcome timeframe

from surgery to discharge (generally no longer than two weeks)

Results posted on

2021-08-18

Participant Flow

84 participants were enrolled and randomized (constitute the safety population). All participants must later meet surgical eligibility for final allocation and analysis (n=62).

Participant milestones

Participant milestones
Measure	Alvimopan Alvimopan: alvimopan pill	Placebo Placebo: placebo pill
Overall Study STARTED	42	42
Overall Study Allocated	30	32
Overall Study COMPLETED	30	32
Overall Study NOT COMPLETED	12	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Alvimopan Alvimopan: alvimopan pill	Placebo Placebo: placebo pill
Overall Study Ineligible by operative criteria	12	10

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alvimopan n=30 Participants Alvimpan Arm	Placebo n=32 Participants Placebo Arm	Total n=62 Participants Total of all reporting groups
Age, Continuous	53 years n=30 Participants	61 years n=32 Participants	57 years n=62 Participants
Sex: Female, Male Female	22 Participants n=30 Participants	12 Participants n=32 Participants	34 Participants n=62 Participants
Sex: Female, Male Male	8 Participants n=30 Participants	20 Participants n=32 Participants	28 Participants n=62 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: from surgery to discharge (generally no longer than two weeks)

Population: Study was terminated early, preliminary data

The later of the time from surgery that the participant first tolerates solid food and the time that the participant first passes a bowel movement.

Outcome measures

Outcome measures
Measure	Alvimopan n=30 Participants Alvimopan: alvimopan pill	Placebo n=32 Participants Placebo: placebo pill
Time to Return of Upper and Lower GI Function	117 hours Interval 102.0 to 158.0	152 hours Interval 134.0 to 204.0

SECONDARY outcome

Timeframe: from surgery to discharge (generally no longer than two weeks)

Population: Study was terminated early, preliminary data

The proportion of patients who do not pass flatus or bowel movement greater than 7 days from the time of surgery.

Outcome measures

Outcome measures
Measure	Alvimopan n=30 Participants Alvimopan: alvimopan pill	Placebo n=32 Participants Placebo: placebo pill
Prolonged Ileus	3 Participants	12 Participants

SECONDARY outcome

Timeframe: from surgery to discharge (generally no longer than two weeks)

Population: Study was terminated early, preliminary data

The time from surgery until: * The time to first flatus * The time to first bowel movement * The time to tolerance of solid food

Outcome measures

Outcome measures
Measure	Alvimopan n=30 Participants Alvimopan: alvimopan pill	Placebo n=32 Participants Placebo: placebo pill
Time to Return of Bowel Function Components Time to first BM	67 hours Interval 62.0 to 89.0	89 hours Interval 71.0 to 114.0
Time to Return of Bowel Function Components Time to tolerance of solid food	117 hours Interval 102.0 to 158.0	149 hours Interval 134.0 to 188.0
Time to Return of Bowel Function Components Time to first flatus	64 hours Interval 51.0 to 93.0	79 hours Interval 63.0 to 97.0

SECONDARY outcome

Timeframe: from surgery to discharge (generally no longer than two weeks)

Population: Study was terminated early, preliminary data

The time from surgery until discharge order written.

Outcome measures

Outcome measures
Measure	Alvimopan n=30 Participants Alvimopan: alvimopan pill	Placebo n=32 Participants Placebo: placebo pill
Time to Discharge	188 hours Interval 147.0 to 212.0	190 hours Interval 187.0 to 236.0

SECONDARY outcome

Timeframe: up to 30 days from surgery

Population: From Safety population (n=84) Study was terminated early, preliminary data

The number and proportion of serious adverse events.

Outcome measures

Outcome measures
Measure	Alvimopan n=42 Participants Alvimopan: alvimopan pill	Placebo n=42 Participants Placebo: placebo pill
Serious Adverse Events	7 Participants	5 Participants

SECONDARY outcome

Timeframe: up to 30 days from surgery

Population: Study was terminated early, data was not collected.

All primary and secondary outcomes will be measured in the following subgroups: * 0 vs. 1 or greater bowel anastomoses * 0 vs. 1 or greater visceral resections * high vs. low amount of postoperative opioid use * epidural vs. no epidural

Outcome measures

Outcome data not reported

Adverse Events

Alvimopan

Serious events: 7 serious events

Other events: 35 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alvimopan n=42 participants at risk Alvimopan: alvimopan pill	Placebo n=42 participants at risk Placebo: placebo pill
Gastrointestinal disorders Abdominal Pain	9.5% 4/42 • Number of events 4 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Gastrointestinal disorders Rectal Perforation	2.4% 1/42 • Number of events 1 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Gastrointestinal disorders Constipation	2.4% 1/42 • Number of events 1 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Renal and urinary disorders Acute Kidney Injury	2.4% 1/42 • Number of events 1 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Gastrointestinal disorders Gastric Perforation	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	2.4% 1/42 • Number of events 1 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Metabolism and nutrition disorders Dehydration	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	2.4% 1/42 • Number of events 1 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Blood and lymphatic system disorders Thromboembolic Event	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	2.4% 1/42 • Number of events 1 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Cardiac disorders Cardiac Arrest	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	2.4% 1/42 • Number of events 1 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.
Surgical and medical procedures Wound Dehiscence	0.00% 0/42 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	2.4% 1/42 • Number of events 1 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.

Other adverse events

Other adverse events
Measure	Alvimopan n=42 participants at risk Alvimopan: alvimopan pill	Placebo n=42 participants at risk Placebo: placebo pill
Surgical and medical procedures Non-Serious Adverse Events	83.3% 35/42 • Number of events 35 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.	88.1% 37/42 • Number of events 37 • 30 days from the the time of surgery CTCAE v 4.03 (grade 3 or higher considered serious adverse event) All participants in the safety population (n=84) were included in the adverse event analysis. Per the protocol, this includes all randomized patients who took at least one dose of the study medication, including screen failures (at the time of surgery) after randomization and subjects withdrawn from the study.

Additional Information

Raymond Diep, Clinical Research Coordinator

University of California, San Diego

Phone: (858) 822-5352

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place