A Phase III Study of the Efficacy and Safety of Remimazolam Compared to Placebo and Midazolam in Colonoscopy Patients

Study Overview
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Brief Summary
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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 patients undergoing a colonoscopy for diagnostic or therapeutic reasons.

Official Title
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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 Patients Undergoing a Colonoscopy

Conditions
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Colonoscopy

Intervention / Treatment
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* Drug: Remimazolam
* Drug: Midazolam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients, aged ≥18, scheduled to undergo a diagnostic or therapeutic colonoscopy (therapeutic procedures could include hemostasis, resection, ablation decompression, foreign body extraction, for example). American Society of Anesthesiologists Score 1 through 3 Body mass index ≤40 kg/m2. For female patients with child-bearing potential, negative result of pregnancy test (serum or urine) as well as use of birth control during the study period (from the time of consent until all specified observations were completed). Patient voluntarily signed and dated an informed consent form that was approved by an Independent Review Board prior to the conduct of any study procedure. Patient was willing and able to comply with study requirements and return for a Follow-up Visit on Day 4 (+3/-1 days) after the colonoscopy. Exclusion Criteria: Patients with a known sensitivity to benzodiazepines, flumazenil, opioids, naloxone, or a medical condition such that these agents were contraindicated. Chronic use of benzodiazepines for any indication (eg, insomnia, anxiety, spasticity). Chronic use of opioids for any indication. Female patients with a positive serum human chorionic gonadotropin pregnancy test at screening or baseline. Lactating female patients. Patients with positive drugs of abuse screen or a positive serum ethanol at baseline. Patient with a history of drug or ethanol abuse within the past 2 years. Patients in receipt of any investigational drug within 30 days or less than seven half-lives (whichever was longer) before screening, or scheduled to receive one during the study period. Participation in any previous clinical trial with remimazolam. Patients with an inability to communicate well in English with the investigator, or deemed unsuitable according to the investigator (in each case providing a reason).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam<br>Remimazolam iv 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance. Fentanyl pre-treatment: 50 μg (or less for elderly/disabled subjects) and 25 μg top-up doses | Drug: Remimazolam<br>* For induction and maintenance of sedation<br>* Other names: Byfavo, CNS7056;|
| Placebo Comparator: Placebo<br>Inactive control arm Fentanyl pre-treatment: 50 μg (or less for elderly/disabled subjects) and 25 μg top-up doses | Drug: Placebo<br>* Inactive control arm<br>|
| Active Comparator: Midazolam<br>Midazolam iv 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 Fentanyl pre-treatment: 50 μg (or less for elderly/disabled subjects) and 25 μg top-up doses | Drug: Midazolam<br>* For induction of maintenance and sedation<br>* Other names: Versed;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success Rates of the Procedure | 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. | From administration of the first dose of the study drug to the end of colonoscopy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Start of Procedure | The time to the start of the procedure after administration of the first dose of randomized study drug | From first dose of study drug until insertion of the colonoscope | 
| Time to Fully Alert | 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 | 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 alert | 
| Time to Ready for Discharge | 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). | 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). |