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

A Study Evaluating the Safety and Efficacy of Remimazolam (CNS 7056) Compared to Placebo and Midazolam in ASA III and IV Patients Undergoing Colonoscopy

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.

Study Overview

• Status: Completed
• Conditions: Colonoscopy
• Intervention / Treatment: Drug: Placebo; Drug: Midazolam; Drug: Remimazolam

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jupiter, Florida, United States, 33458
      • Jupiter Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 51000
      • Indiana University Division of Gastroenterology/Hepatology
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remimazolam; Remimazolam 2.5 - 5.0 mg initially, followed by 1.25 - 2.5 mg top-up doses as required to maintain sedation. Fentanyl pre-treatment: 25-50 μg (or less for elderly/disabled subjects), and 25 μg top-up doses	Drug: Remimazolam; Other Names: CNS7056
Active Comparator: Midazolam; Midazolam 1.0 mg initially, followed by 0.5 mg top-up doses as required to maintain sedation. Fentanyl pre-treatment: 25-50 μg (or less for elderly/disabled subjects), and 25 μg top-up doses	Drug: Midazolam; Other Names: Versed
Placebo Comparator: Placebo; Placebo administered in double-blind manner. Fentanyl pre-treatment: 25-50 μg (or less for elderly/disabled subjects), and 25 μg top-up doses	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	From first dose of study drug until the end of colonoscopy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Start of Procedure	The time from the first administration of the study drug to the beginning of the colonoscopy	From the first administration of the study drug to the beginning of the colonoscopy
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	From the last injection of the study drug AND from end of colonoscopy until the patient has recovered to fully alert

Collaborators and Investigators

• Sponsor: Paion UK Ltd.
• Collaborators: Premier Research Group plc
• Investigators: Principal Investigator: Douglas Rex, MD, IU Health University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: August 19, 2015
• First Submitted That Met QC Criteria: August 25, 2015
• First Posted (Estimate): August 26, 2015

Study Record Updates

• Last Update Posted (Actual): September 30, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: CNS7056-015

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No