Trial Outcomes & Findings for Multiple Dose Safety and Efficacy Study Evaluating CNS 7056 Versus Midazolam in Patients Undergoing Colonoscopy (NCT NCT01145222)
NCT ID: NCT01145222
Last Updated: 2019-01-08
Results Overview
Success of the procedure is a composite endpoint consisting of: Modified Observer's Assessment for Alertness/Sedation (MOAA/S) scores ≤4 on three consecutive measurements after administration of study drug AND completion of the endoscopy procedure AND no requirement for rescue sedative medication AND no requirement for manual or mechanical ventilation
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
162 participants
Primary outcome timeframe
From start of study drug injection to patient discharge
Results posted on
2019-01-08
Participant Flow
Participant milestones
| Measure |
Remimazolam 8.0/3.0 mg
Double-blind Remimazolam iv arm: 8 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Remimazolam 7.0/2.0 mg
Double-blind Remimazolam iv arm: 7 mg for sedation induction, and 2 mg top-ups for sedation maintenance
|
Remimazolam 5.0/3.0 mg
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Midazolam 2.5/1.0
Double-blind Midazolam iv arm: 2.5 mg for sedation induction, and 1.0 mg top-ups for sedation maintenance.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
40
|
40
|
41
|
41
|
|
Overall Study
Safety Population
|
40
|
40
|
40
|
41
|
|
Overall Study
Intention to Treat (ITT) Population
|
40
|
40
|
40
|
40
|
|
Overall Study
COMPLETED
|
40
|
40
|
40
|
40
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
1
|
1
|
Reasons for withdrawal
| Measure |
Remimazolam 8.0/3.0 mg
Double-blind Remimazolam iv arm: 8 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Remimazolam 7.0/2.0 mg
Double-blind Remimazolam iv arm: 7 mg for sedation induction, and 2 mg top-ups for sedation maintenance
|
Remimazolam 5.0/3.0 mg
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Midazolam 2.5/1.0
Double-blind Midazolam iv arm: 2.5 mg for sedation induction, and 1.0 mg top-ups for sedation maintenance.
|
|---|---|---|---|---|
|
Overall Study
Procedure not done (no anesthesiologist)
|
0
|
0
|
1
|
0
|
|
Overall Study
Poor bowel preparation
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Multiple Dose Safety and Efficacy Study Evaluating CNS 7056 Versus Midazolam in Patients Undergoing Colonoscopy
Baseline characteristics by cohort
| Measure |
Remimazolam 8.0/3.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 8 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Remimazolam 7.0/2.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 7 mg for sedation induction, and 2 mg top-ups for sedation maintenance
|
Remimazolam 5.0/3.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Midazolam 2.5/1.0
n=41 Participants
Double-blind Midazolam iv arm: 2.5 mg for sedation induction, and 1 mg top-ups for sedation maintenance.
|
Total
n=161 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
54.5 years
STANDARD_DEVIATION 11.22 • n=5 Participants
|
54.5 years
STANDARD_DEVIATION 8.07 • n=7 Participants
|
54.0 years
STANDARD_DEVIATION 10.30 • n=5 Participants
|
55.5 years
STANDARD_DEVIATION 5.86 • n=4 Participants
|
54.6 years
STANDARD_DEVIATION 9.02 • n=21 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
20 Participants
n=4 Participants
|
89 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
72 Participants
n=21 Participants
|
|
Region of Enrollment
United States
|
40 participants
n=5 Participants
|
40 participants
n=7 Participants
|
40 participants
n=5 Participants
|
41 participants
n=4 Participants
|
161 participants
n=21 Participants
|
|
Height
|
169.15 cm
STANDARD_DEVIATION 11.0 • n=5 Participants
|
168.18 cm
STANDARD_DEVIATION 8.3 • n=7 Participants
|
169.01 cm
STANDARD_DEVIATION 11.3 • n=5 Participants
|
169.87 cm
STANDARD_DEVIATION 10.1 • n=4 Participants
|
169.06 cm
STANDARD_DEVIATION 10.2 • n=21 Participants
|
|
Weight
|
79.68 kg
STANDARD_DEVIATION 13.4 • n=5 Participants
|
76.23 kg
STANDARD_DEVIATION 11.6 • n=7 Participants
|
76.79 kg
STANDARD_DEVIATION 14.5 • n=5 Participants
|
76.95 kg
STANDARD_DEVIATION 13.6 • n=4 Participants
|
77.41 kg
STANDARD_DEVIATION 13.3 • n=21 Participants
|
|
Body Mass Index (BMI)
|
27.79 Kg/m2
STANDARD_DEVIATION 3.451 • n=5 Participants
|
27.02 Kg/m2
STANDARD_DEVIATION 4.042 • n=7 Participants
|
26.73 Kg/m2
STANDARD_DEVIATION 3.063 • n=5 Participants
|
26.58 Kg/m2
STANDARD_DEVIATION 3.515 • n=4 Participants
|
27.03 Kg/m2
STANDARD_DEVIATION 3.533 • n=21 Participants
|
PRIMARY outcome
Timeframe: From start of study drug injection to patient dischargePopulation: Analysis Population is the ITT Population
Success of the procedure is a composite endpoint consisting of: Modified Observer's Assessment for Alertness/Sedation (MOAA/S) scores ≤4 on three consecutive measurements after administration of study drug AND completion of the endoscopy procedure AND no requirement for rescue sedative medication AND no requirement for manual or mechanical ventilation
Outcome measures
| Measure |
Remimazolam 8.0/3.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 8 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Remimazolam 7.0/2.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 7 mg for sedation induction, and 2 mg top-ups for sedation maintenance
|
Remimazolam 5.0/3.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Midazolam 2.5/1.0
n=40 Participants
Double-blind Midazolam iv arm: 2.5 mg for sedation induction, and 1 mg top-ups for sedation maintenance.
|
|---|---|---|---|---|
|
Success Rates of the Procedure
|
37 Participants
|
38 Participants
|
39 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: From last injection of double-blind study medication until fully alert criteria are reachedPopulation: Analysis Population is the ITT Population
Time to first of 3 consecutive MOAA/S scores of 5 after the last injection of double-blind study medication
Outcome measures
| Measure |
Remimazolam 8.0/3.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 8 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Remimazolam 7.0/2.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 7 mg for sedation induction, and 2 mg top-ups for sedation maintenance
|
Remimazolam 5.0/3.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Midazolam 2.5/1.0
n=40 Participants
Double-blind Midazolam iv arm: 2.5 mg for sedation induction, and 1 mg top-ups for sedation maintenance.
|
|---|---|---|---|---|
|
Time to Fully Alert
|
13.6 minutes
Standard Deviation 7.48
|
11.3 minutes
Standard Deviation 5.69
|
13.3 minutes
Standard Deviation 7.21
|
15.2 minutes
Standard Deviation 7.43
|
SECONDARY outcome
Timeframe: After the Last Injection of Double-Blind Study Medication AND after end of colonoscopy until first of 3 consecutive Aldrete scores ≥ 9Population: Analysis Population is the ITT Population
Time of the first of 3 consecutive Aldrete scores ≥ 9
Outcome measures
| Measure |
Remimazolam 8.0/3.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 8 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Remimazolam 7.0/2.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 7 mg for sedation induction, and 2 mg top-ups for sedation maintenance
|
Remimazolam 5.0/3.0 mg
n=40 Participants
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Midazolam 2.5/1.0
n=40 Participants
Double-blind Midazolam iv arm: 2.5 mg for sedation induction, and 1 mg top-ups for sedation maintenance.
|
|---|---|---|---|---|
|
Time to Ready for Discharge
After last injection
|
14.6 minutes
Standard Deviation 8.52
|
12.4 minutes
Standard Deviation 6.72
|
11.3 minutes
Standard Deviation 4.86
|
15.3 minutes
Standard Deviation 8.13
|
|
Time to Ready for Discharge
After end of colonoscopy
|
5.0 minutes
Standard Deviation 6.29
|
4.6 minutes
Standard Deviation 4.58
|
3.8 minutes
Standard Deviation 4.16
|
5.5 minutes
Standard Deviation 6.59
|
Adverse Events
Remimazolam 8.0/3.0 mg
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Remimazolam 7.0/2.0 mg
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Remimazolam 5.0/3.0 mg
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Midazolam 2.5/1.0
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Remimazolam 8.0/3.0 mg
n=40 participants at risk
Double-blind Remimazolam iv arm: 8 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Remimazolam 7.0/2.0 mg
n=40 participants at risk
Double-blind Remimazolam iv arm: 7 mg for sedation induction, and 2 mg top-ups for sedation maintenance
|
Remimazolam 5.0/3.0 mg
n=40 participants at risk
Double-blind Remimazolam iv arm: 5 mg for sedation induction, and 3 mg top-ups for sedation maintenance
|
Midazolam 2.5/1.0
n=41 participants at risk
Double-blind Midazolam iv arm: 2.5 mg for sedation induction, and 1 mg top-ups for sedation maintenance.
|
|---|---|---|---|---|
|
Cardiac disorders
Bradycardia
|
7.5%
3/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
2.5%
1/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
0.00%
0/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
0.00%
0/41 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
|
Gastrointestinal disorders
Abdominal pain
|
2.5%
1/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
5.0%
2/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
7.5%
3/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
0.00%
0/41 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
|
Gastrointestinal disorders
Vomiting
|
2.5%
1/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
5.0%
2/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
7.5%
3/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
4.9%
2/41 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
|
Nervous system disorders
Headache
|
2.5%
1/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
7.5%
3/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
7.5%
3/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
4.9%
2/41 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
|
Vascular disorders
Hypertension
|
7.5%
3/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
0.00%
0/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
2.5%
1/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
9.8%
4/41 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
|
Gastrointestinal disorders
Nausea
|
7.5%
3/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
5.0%
2/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
5.0%
2/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
2.4%
1/41 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
|
Nervous system disorders
Dizziness
|
0.00%
0/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
2.5%
1/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
5.0%
2/40 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
|
0.00%
0/41 • Treatment-emergent Adverse Events (TEAEs) were collected from first dose of study drug until Day 4 ± 3 days, and were followed until resolution of any ongoing TEAE up to 30 days
Total number of participants affected with Other (Not Including Serious) Adverse Events represents overall number of participants with non-serious TEAEs 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 for publication, presentation or use, sponsor shall review and comment any proposed oral or written publication, which period may be extended for an additional 30 days. To seek patent protection, sponsor shall have the right to delay the proposed publication for an additional 60 days.
- Publication restrictions are in place
Restriction type: OTHER