Colonoscopy
Conditions
Brief summary
A prospective, double-blind, randomized, placebo and active controlled, multi-center, parallel group study comparing remimazolam to placebo, with an additional open-label arm for midazolam, in American Society of Anesthesiologists (ASA) Grade III and IV patients (ASA status evaluated by an anesthesiologist not otherwise involved in the study) undergoing a colonoscopy for diagnostic or therapeutic reasons.
Interventions
DRUGRemimazolam
DRUGMidazolam
DRUGPlacebo
Sponsors
Premier Research
Paion UK Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female patients, aged ≥18, scheduled to undergo a diagnostic or therapeutic colonoscopy (therapeutic procedures may include hemostasis, resection, ablation decompression, and foreign body extraction, for example). 2. ASA grade III/IV 1. ASA III patients are patients with severe systemic disease eg patients who, in the judgment of the Principal Investigator (PI), have significant enough systemic disease to warrant performing the colonoscopy procedure only in a facility which has post-procedure inpatient capability. ASA III physical status classification encompasses a wide range of potential patient co-morbidities some of which may make the selection of a facility with post-procedure inpatient capability preferable. By definition, ASA III patients have one or more moderate to severe systemic diseases which potentially cause substantial functional limitation. Examples may include poorly controlled diabetes or hypertension, moderate to severe chronic obstructive pulmonary disease, active hepatitis, heart failure or coronary artery disease (including implanted pacemaker and/or stent, recent myocardial infarction) cerebrovascular accident, or end stage renal disease requiring dialysis. 2. ASA IV patients are patients with severe systemic disease that is a constant threat to life eg at least one severe disease that is poorly controlled or at end stage; possible risk of death; unstable angina; symptomatic chronic obstructive pulmonary disease; symptomatic chronic heart failure; hepatorenal failure. 3. For all female patients, negative result of urine or serum pregnancy test. Additionally, for women with child-bearing potential only, use of birth control during the study period (from the time of consent until all specified observations are completed). 4. Patient voluntarily signs and dates an informed consent form (ICF) that is approved by an investigational review board (IRB) prior to the conduct of any study procedure. 5. Patient is willing and able to comply with study requirements and will be available for a Follow-up Visit on Day 1 (+ 1 day) and Follow-up Phone call (Day 4 +/- 3 days) after the colonoscopy.
Exclusion criteria
1. Patients with a known sensitivity to benzodiazepines, flumazenil, opioids, naloxone, or a medical condition such that these agents are contraindicated. 2. Female patients with a positive pregnancy test at screening or baseline and lactating female patients. 3. Patients clearly acutely intoxicated with alcohol or drugs of abuse at baseline. 4. Patients in receipt of any investigational drug within 30 days or less than 7 half-lives (whichever is longer) before Screening, or scheduled to receive one during the study period. 5. Participation in any previous clinical trial with remimazolam. 6. Patients with an inability to communicate well with the Investigator, or deemed unsuitable according to the Investigator (in each case providing a reason).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Success Rates of the Procedure | From first dose of study drug until the end of colonoscopy | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Start of Procedure | From the first administration of the study drug to the beginning of the colonoscopy | The time from the first administration of the study drug to the beginning of the colonoscopy |
| Time to Fully Alert | From the last injection of the study drug AND from end of colonoscopy until the patient has recovered to fully alert | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Remimazolam Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation. | 31 |
| Placebo Placebo administered in double-blind manner. | 16 |
| Midazolam Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation. | 30 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Did not receive trial medication | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Remimazolam | Placebo | Midazolam | Total |
|---|---|---|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 8.65 | 63.0 years STANDARD_DEVIATION 8.37 | 61.5 years STANDARD_DEVIATION 10.6 | 62.5 years STANDARD_DEVIATION 9.32 |
| Age, Customized <65 years | 18 Participants | 9 Participants | 19 Participants | 46 Participants |
| Age, Customized ≥65 years | 13 Participants | 7 Participants | 11 Participants | 31 Participants |
| American Society of Anesthesiologists (ASA) Classification ASA Class III | 16 Participants | 9 Participants | 15 Participants | 40 Participants |
| American Society of Anesthesiologists (ASA) Classification ASA Class IV | 15 Participants | 7 Participants | 15 Participants | 37 Participants |
| Body Mass Index (BMI) | 30.9 Kg/m2 STANDARD_DEVIATION 8.28 | 30.8 Kg/m2 STANDARD_DEVIATION 5.53 | 30.8 Kg/m2 STANDARD_DEVIATION 6.75 | 30.8 Kg/m2 STANDARD_DEVIATION 7.11 |
| Height | 171.1 cm STANDARD_DEVIATION 10.07 | 171.8 cm STANDARD_DEVIATION 7.72 | 168.4 cm STANDARD_DEVIATION 10.32 | 170.2 cm STANDARD_DEVIATION 9.72 |
| Region of Enrollment United States | 31 participants | 16 participants | 30 participants | 77 participants |
| Sex: Female, Male Female | 14 Participants | 4 Participants | 16 Participants | 34 Participants |
| Sex: Female, Male Male | 17 Participants | 12 Participants | 14 Participants | 43 Participants |
| Weight | 91.0 kg STANDARD_DEVIATION 28.14 | 94.0 kg STANDARD_DEVIATION 26.11 | 87.9 kg STANDARD_DEVIATION 23.91 | 90.4 kg STANDARD_DEVIATION 25.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 16 | 0 / 30 |
| other Total, other adverse events | 28 / 31 | 13 / 16 | 26 / 30 |
| serious Total, serious adverse events | 0 / 31 | 0 / 16 | 1 / 30 |
Outcome results
Primary
Success Rates of the Procedure
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)
Time frame: From first dose of study drug until the end of colonoscopy
Population: All patients who were randomised, and analysed as randomised.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Remimazolam | Success Rates of the Procedure | 27 Participants |
| Placebo | Success Rates of the Procedure | 0 Participants |
| Midazolam | Success Rates of the Procedure | 4 Participants |
Secondary
Time to Fully Alert
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
Time frame: 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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Remimazolam | Time to Fully Alert | After last dose of trial or rescue sedative | 11.0 minutes |
| Remimazolam | Time to Fully Alert | After the end of colonoscopy | 3.0 minutes |
| Placebo | Time to Fully Alert | After last dose of trial or rescue sedative | 18.0 minutes |
| Placebo | Time to Fully Alert | After the end of colonoscopy | 5.3 minutes |
| Midazolam | Time to Fully Alert | After the end of colonoscopy | 7.0 minutes |
| Midazolam | Time to Fully Alert | After last dose of trial or rescue sedative | 18.8 minutes |
Secondary
Time to Start of Procedure
The time from the first administration of the study drug to the beginning of the colonoscopy
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Remimazolam | Time to Start of Procedure | 5.0 minutes |
| Placebo | Time to Start of Procedure | 18.3 minutes |
| Midazolam | Time to Start of Procedure | 19.0 minutes |