Trial Outcomes & Findings for Safety and Efficacy of Remimazolam in ASA III and IV Patients Undergoing Colonoscopy (NCT NCT02532647)

Last Updated: 2020-09-30

Results Overview

The success of the procedure, as measured by completion of the colonoscopy procedure, AND no requirement for a rescue sedative medication, AND no requirement of more than 5 doses of study medication within any 15 minute window. (For midazolam: 3 doses within any 12 minute window)

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

79 participants

Primary outcome timeframe

From first dose of study drug until the end of colonoscopy

Results posted on

2020-09-30

Participant Flow

Participant milestones

Participant milestones
Measure	Remimazolam Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation.	Placebo Placebo administered in double-blind manner.	Midazolam Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation.
Overall Study STARTED	32	16	31
Overall Study Safety Population	31	16	30
Overall Study COMPLETED	31	16	30
Overall Study NOT COMPLETED	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Remimazolam Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation.	Placebo Placebo administered in double-blind manner.	Midazolam Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation.
Overall Study Did not receive trial medication	1	0	1

Baseline Characteristics

Safety and Efficacy of Remimazolam in ASA III and IV Patients Undergoing Colonoscopy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Remimazolam n=31 Participants Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation.	Placebo n=16 Participants Placebo administered in double-blind manner.	Midazolam n=30 Participants Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation.	Total n=77 Participants Total of all reporting groups
Age, Continuous	63.1 years STANDARD_DEVIATION 8.65 • n=5 Participants	63.0 years STANDARD_DEVIATION 8.37 • n=7 Participants	61.5 years STANDARD_DEVIATION 10.60 • n=5 Participants	62.5 years STANDARD_DEVIATION 9.32 • n=4 Participants
Age, Customized <65 years	18 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants	46 Participants n=4 Participants
Age, Customized ≥65 years	13 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	31 Participants n=4 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants	34 Participants n=4 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	43 Participants n=4 Participants
Region of Enrollment United States	31 participants n=5 Participants	16 participants n=7 Participants	30 participants n=5 Participants	77 participants n=4 Participants
Height	171.1 cm STANDARD_DEVIATION 10.07 • n=5 Participants	171.8 cm STANDARD_DEVIATION 7.72 • n=7 Participants	168.4 cm STANDARD_DEVIATION 10.32 • n=5 Participants	170.2 cm STANDARD_DEVIATION 9.72 • n=4 Participants
Weight	91.0 kg STANDARD_DEVIATION 28.14 • n=5 Participants	94.0 kg STANDARD_DEVIATION 26.11 • n=7 Participants	87.9 kg STANDARD_DEVIATION 23.91 • n=5 Participants	90.4 kg STANDARD_DEVIATION 25.90 • n=4 Participants
Body Mass Index (BMI)	30.9 Kg/m2 STANDARD_DEVIATION 8.28 • n=5 Participants	30.8 Kg/m2 STANDARD_DEVIATION 5.53 • n=7 Participants	30.8 Kg/m2 STANDARD_DEVIATION 6.75 • n=5 Participants	30.8 Kg/m2 STANDARD_DEVIATION 7.11 • n=4 Participants
American Society of Anesthesiologists (ASA) Classification ASA Class III	16 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants	40 Participants n=4 Participants
American Society of Anesthesiologists (ASA) Classification ASA Class IV	15 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants	37 Participants n=4 Participants

PRIMARY outcome

Timeframe: From first dose of study drug until the end of colonoscopy

Population: All patients who were randomised, and analysed as randomised.

Outcome measures

Outcome measures
Measure	Remimazolam n=32 Participants Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation.	Placebo n=16 Participants Placebo administered in double-blind manner.	Midazolam n=31 Participants Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation.
Success Rates of the Procedure	27 Participants	0 Participants	4 Participants

SECONDARY outcome

Timeframe: From the first administration of the study drug to the beginning of the colonoscopy

Population: Patients who did not reach the endpoint are excluded from this analysis.

The time from the first administration of the study drug to the beginning of the colonoscopy

Outcome measures

Outcome measures
Measure	Remimazolam n=31 Participants Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation.	Placebo n=16 Participants Placebo administered in double-blind manner.	Midazolam n=30 Participants Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation.
Time to Start of Procedure	5.0 minutes Interval 4.0 to 8.0	18.3 minutes Interval 17.5 to 21.0	19.0 minutes Interval 19.0 to 19.0

SECONDARY outcome

Timeframe: From the last injection of the study drug AND from end of colonoscopy until the patient has recovered to fully alert

Population: Patients who did not reach the endpoint are censored at last observation.

Time to first of 3 Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores of 5 after the end of colonoscopy procedure (colonoscope out) and after the last injection of study drug

Outcome measures

Outcome measures
Measure	Remimazolam n=31 Participants Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation.	Placebo n=16 Participants Placebo administered in double-blind manner.	Midazolam n=30 Participants Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation.
Time to Fully Alert After last dose of trial or rescue sedative	11.0 minutes Interval 8.8 to 12.0	18.0 minutes Interval 14.0 to 25.0	18.8 minutes Interval 15.0 to 26.0
Time to Fully Alert After the end of colonoscopy	3.0 minutes Interval 2.0 to 4.0	5.3 minutes Interval 4.0 to 12.0	7.0 minutes Interval 4.0 to 12.0

Adverse Events

Remimazolam

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Midazolam

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Remimazolam n=31 participants at risk Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation.	Placebo n=16 participants at risk Placebo administered in double-blind manner.	Midazolam n=30 participants at risk Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation.
Blood and lymphatic system disorders Anaemia	0.00% 0/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	0.00% 0/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	3.3% 1/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms

Other adverse events

Other adverse events
Measure	Remimazolam n=31 participants at risk Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation.	Placebo n=16 participants at risk Placebo administered in double-blind manner.	Midazolam n=30 participants at risk Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation.
Vascular disorders Hypotension	58.1% 18/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	68.8% 11/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	56.7% 17/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms
Vascular disorders Hypertension	41.9% 13/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	37.5% 6/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	43.3% 13/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms
Vascular disorders Diastolic hypertension	9.7% 3/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	0.00% 0/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	0.00% 0/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms
Vascular disorders Diastolic hypotension	3.2% 1/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	6.2% 1/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	0.00% 0/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms
Vascular disorders Systolic hypertension	6.5% 2/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	0.00% 0/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	0.00% 0/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	19.4% 6/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	12.5% 2/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	26.7% 8/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms
Cardiac disorders Bradycardia	3.2% 1/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	6.2% 1/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	13.3% 4/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms
Cardiac disorders Tachycardia	0.00% 0/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	12.5% 2/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	0.00% 0/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms
Investigations Respiratory rate decreased	3.2% 1/31 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	6.2% 1/16 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms	6.7% 2/30 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug medication until Day 4 (+ 3 days), and were followed until events resolved, became stable, or could be explained by another known cause(s) Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with TEAEs reported with a threshold of 5% in any of the arms

Additional Information

Trial Information

PAION UK Ltd

Email: [email protected]

Results disclosure agreements

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