Trial Outcomes & Findings for A Phase III Study of the Efficacy and Safety of Remimazolam Compared to Placebo and Midazolam in Colonoscopy Patients (NCT NCT02290873)
NCT ID: NCT02290873
Last Updated: 2020-10-20
Results Overview
Success of the Procedure is measured by completion of colonoscopy, no requirement for an alternative sedative and no requirement for more than 5 top-ups of study medication within any 15 minute period in the blinded arms (remimazolam/placebo) or no requirement for more than 3 doses within any 12 minute window in the midazolam arm.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
461 participants
Primary outcome timeframe
From administration of the first dose of the study drug to the end of colonoscopy
Results posted on
2020-10-20
Participant Flow
Participant milestones
| Measure |
Remimazolam
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance.
|
Placebo
Double-blind Placebo iv arm: as an inactive control
|
Midazolam
Open-label Midazolam iv arm: 1.75 mg\* for sedation induction and 1.0 mg\* for sedation maintenance.
\*1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill
|
|---|---|---|---|
|
Overall Study
STARTED
|
298
|
60
|
103
|
|
Overall Study
Modified Intention to Treat (mITT)
|
296
|
60
|
102
|
|
Overall Study
Safety Population
|
296
|
60
|
102
|
|
Overall Study
COMPLETED
|
296
|
59
|
101
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
2
|
Reasons for withdrawal
| Measure |
Remimazolam
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance.
|
Placebo
Double-blind Placebo iv arm: as an inactive control
|
Midazolam
Open-label Midazolam iv arm: 1.75 mg\* for sedation induction and 1.0 mg\* for sedation maintenance.
\*1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
|
Overall Study
Nellcor device error
|
1
|
0
|
0
|
|
Overall Study
Esophagogastroduodenoscopy was added
|
1
|
0
|
0
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
Baseline Characteristics
A Phase III Study of the Efficacy and Safety of Remimazolam Compared to Placebo and Midazolam in Colonoscopy Patients
Baseline characteristics by cohort
| Measure |
Remimazolam
n=296 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance.
|
Placebo
n=60 Participants
Double-blind Placebo iv arm: inactive control arm
|
Midazolam
n=102 Participants
Open-label Midazolam iv arm: 1.75 mg\* for sedation induction and 1.0 mg\* for sedation maintenance.
\*1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill
|
Total
n=458 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
54.4 years
STANDARD_DEVIATION 10.12 • n=93 Participants
|
56 years
STANDARD_DEVIATION 9.51 • n=4 Participants
|
55.6 years
STANDARD_DEVIATION 10.15 • n=27 Participants
|
54.9 years
STANDARD_DEVIATION 10.05 • n=483 Participants
|
|
Age, Customized
<65 years
|
254 Participants
n=93 Participants
|
53 Participants
n=4 Participants
|
88 Participants
n=27 Participants
|
395 Participants
n=483 Participants
|
|
Age, Customized
≥65 years
|
42 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
63 Participants
n=483 Participants
|
|
Sex: Female, Male
Female
|
149 Participants
n=93 Participants
|
35 Participants
n=4 Participants
|
56 Participants
n=27 Participants
|
240 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
147 Participants
n=93 Participants
|
25 Participants
n=4 Participants
|
46 Participants
n=27 Participants
|
218 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
296 participants
n=93 Participants
|
60 participants
n=4 Participants
|
102 participants
n=27 Participants
|
458 participants
n=483 Participants
|
|
Weight
|
83.2 Kg
STANDARD_DEVIATION 17.39 • n=93 Participants
|
84.6 Kg
STANDARD_DEVIATION 19.9 • n=4 Participants
|
81.9 Kg
STANDARD_DEVIATION 16.24 • n=27 Participants
|
83.1 Kg
STANDARD_DEVIATION 17.47 • n=483 Participants
|
|
Height
|
170.1 cm
STANDARD_DEVIATION 10.36 • n=93 Participants
|
167.8 cm
STANDARD_DEVIATION 10.24 • n=4 Participants
|
169.5 cm
STANDARD_DEVIATION 11.15 • n=27 Participants
|
169.6 cm
STANDARD_DEVIATION 10.53 • n=483 Participants
|
|
Body Max Index (BMI)
|
28.9 kg/m2
STANDARD_DEVIATION 4.72 • n=93 Participants
|
30 kg/m2
STANDARD_DEVIATION 5.31 • n=4 Participants
|
28.8 kg/m2
STANDARD_DEVIATION 4.75 • n=27 Participants
|
29 kg/m2
STANDARD_DEVIATION 4.81 • n=483 Participants
|
PRIMARY outcome
Timeframe: From administration of the first dose of the study drug to the end of colonoscopySuccess of the Procedure is measured by completion of colonoscopy, no requirement for an alternative sedative and no requirement for more than 5 top-ups of study medication within any 15 minute period in the blinded arms (remimazolam/placebo) or no requirement for more than 3 doses within any 12 minute window in the midazolam arm.
Outcome measures
| Measure |
Remimazolam
n=298 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance.
|
Placebo
n=60 Participants
Double-blind Placebo iv arm: as an inactive control arm
|
Midazolam
n=103 Participants
Open-label Midazolam iv arm: 1.75 mg\* for sedation induction and 1.0 mg\* for sedation maintenance.
\*1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill
|
|---|---|---|---|
|
Success Rates of the Procedure
|
272 Participants
|
1 Participants
|
26 Participants
|
SECONDARY outcome
Timeframe: From first dose of study drug until insertion of the colonoscopePopulation: Patients who do not reach the endpoint are excluded from the analysis.
The time to the start of the procedure after administration of the first dose of randomized study drug
Outcome measures
| Measure |
Remimazolam
n=296 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance.
|
Placebo
n=60 Participants
Double-blind Placebo iv arm: as an inactive control arm
|
Midazolam
n=102 Participants
Open-label Midazolam iv arm: 1.75 mg\* for sedation induction and 1.0 mg\* for sedation maintenance.
\*1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill
|
|---|---|---|---|
|
Time to Start of Procedure
|
4 minutes
Interval 3.0 to 6.0
|
19.5 minutes
Interval 17.0 to 23.0
|
19 minutes
Interval 12.0 to 21.0
|
SECONDARY outcome
Timeframe: From the end of colonoscopy (colonoscope out) until the patient has recovered to fully alert and from the last injection of the study drug or rescue sedative medication until the patient has recovered to fully alertPopulation: Patients who do not reach the endpoint are censored at last MOAA/S
The time to fully alert (time to first of three consecutive Modified Observer's Assessment of Alertness/Sedation \[MOAA/S\] scores of 5) after the end of colonoscopy procedure \[colonoscope out\], and after the last dose of study drug or rescue sedative medication
Outcome measures
| Measure |
Remimazolam
n=296 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance.
|
Placebo
n=60 Participants
Double-blind Placebo iv arm: as an inactive control arm
|
Midazolam
n=102 Participants
Open-label Midazolam iv arm: 1.75 mg\* for sedation induction and 1.0 mg\* for sedation maintenance.
\*1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill
|
|---|---|---|---|
|
Time to Fully Alert
After the end of colonoscopy
|
6 minutes
Interval 5.0 to 7.0
|
15 minutes
Interval 13.0 to 21.0
|
13 minutes
Interval 11.0 to 16.0
|
|
Time to Fully Alert
After last dose of study drug or rescue sedative
|
14 minutes
Interval 13.0 to 14.0
|
28 minutes
Interval 24.0 to 32.0
|
24 minutes
Interval 22.0 to 26.0
|
SECONDARY outcome
Timeframe: From the end of the colonoscopy until discharge (expected to be the same day). After the last dose of study drug or rescue sedative, until discharge (expected to be the same day).The time after the end of colonoscopy procedure (colonoscope out) and after the last injection of study drug or rescue sedative medication, until discharge (defined as ability to walk unassisted).
Outcome measures
| Measure |
Remimazolam
n=296 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance.
|
Placebo
n=60 Participants
Double-blind Placebo iv arm: as an inactive control arm
|
Midazolam
n=102 Participants
Open-label Midazolam iv arm: 1.75 mg\* for sedation induction and 1.0 mg\* for sedation maintenance.
\*1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill
|
|---|---|---|---|
|
Time to Ready for Discharge
After the end of colonoscopy procedure
|
44 minutes
Interval 42.0 to 46.0
|
49 minutes
Interval 44.0 to 54.0
|
48 minutes
Interval 41.0 to 51.0
|
|
Time to Ready for Discharge
After last dose of study drug or rescue sedative
|
51 minutes
Interval 49.0 to 54.0
|
60.5 minutes
Interval 55.0 to 67.0
|
57 minutes
Interval 53.0 to 61.0
|
Adverse Events
Remimazolam
Serious events: 0 serious events
Other events: 218 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 47 other events
Deaths: 0 deaths
Midazolam
Serious events: 0 serious events
Other events: 93 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Remimazolam
n=296 participants at risk
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance.
|
Placebo
n=60 participants at risk
Double-blind Placebo iv arm: as an inactive control
|
Midazolam
n=102 participants at risk
Open-label Midazolam iv arm: 1.75 mg\* for sedation induction and 1.0 mg\* for sedation maintenance.
\*1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill
|
|---|---|---|---|
|
Vascular disorders
Hypotension
|
38.9%
115/296 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
41.7%
25/60 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
61.8%
63/102 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
|
Vascular disorders
Hypertension
|
19.9%
59/296 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
28.3%
17/60 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
17.6%
18/102 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
|
Cardiac disorders
Bradycardia
|
11.1%
33/296 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
11.7%
7/60 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
15.7%
16/102 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
|
Vascular disorders
Diastolic Hypertension
|
9.8%
29/296 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
10.0%
6/60 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
8.8%
9/102 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
|
Vascular disorders
Diastolic Hypotension
|
7.8%
23/296 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
6.7%
4/60 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
8.8%
9/102 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
|
Vascular disorders
Systolic hypertension
|
5.4%
16/296 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
8.3%
5/60 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
5.9%
6/102 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
|
Cardiac disorders
Tachycardia
|
7.8%
23/296 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
11.7%
7/60 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
12.7%
13/102 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
|
Gastrointestinal disorders
Nausea
|
1.7%
5/296 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
6.7%
4/60 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
2.0%
2/102 • From first dose of study drug until Day 4, or resolution of any ongoing adverse events
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a non serious Treatment-emergent Adverse Event (TEAE). The listing of participants with Preferred Term (PT)TEAEs is reported with a threshold of 5% in any of the arms
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee At least 60 days prior to submission of communications, sponsor shall review and comment on the communications. Sponsor shall have the right to require institution and investigator to remove specifically identified confidential information and to delay the proposed publication an additional 60 days to enable sponsor to seek patent protection.
- Publication restrictions are in place
Restriction type: OTHER