Clinical trial NCT02290873: A Phase III Study of the Efficacy and Safety of Remimazolam Compared to Placebo and Midazolam in Colonoscopy Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colonoscopy
Lead sponsor: Paion UK Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Premier Research Group plc
First posted: 2014-11-14
Enrollment: 461
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 patients undergoing a colonoscopy for diagnostic or therapeutic reasons.


Eligibility criteria: 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).

Primary outcomes:
measure: Success Rates of the Procedure
timeFrame: From administration of the first dose of the study drug to the end of colonoscopy
Secondary outcomes:
measure: Time to Start of Procedure
timeFrame: From first dose of study drug until insertion of the colonoscope
measure: Time to Fully Alert
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 alert
measure: Time to Ready for Discharge
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).
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama
state: Alabama
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute
state: California
city: Chula Vista
country: United States
facility: Precision Research Institute
state: California
city: San Diego
country: United States
facility: Precision Research Institute
state: California
city: Jacksonville
country: United States
facility: Borland-Grover Clinic, P.A
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health
state: Indiana
city: Monroe
country: United States
facility: Delta Research Partners Inc
state: Louisiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson Medical College
state: Pennsylvania
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Chesapeake
country: United States
facility: Gastroenterology Associates of Tidewater
state: Virginia
Study officials:
affiliation: Indiana University School of Medicine
name: Douglas K Rex, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Antonik LJ, Goldwater DR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics. Anesth Analg. 2012 Aug;115(2):274-83. doi: 10.1213/ANE.0b013e31823f0c28. Epub 2011 Dec 20.
citation: Wiltshire HR, Kilpatrick GJ, Tilbrook GS, Borkett KM. A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation. Anesth Analg. 2012 Aug;115(2):284-96. doi: 10.1213/ANE.0b013e318241f68a. Epub 2012 Jan 16.
citation: Worthington MT, Antonik LJ, Goldwater DR, Lees JP, Wilhelm-Ogunbiyi K, Borkett KM, Mitchell MC. A phase Ib, dose-finding study of multiple doses of remimazolam (CNS 7056) in volunteers undergoing colonoscopy. Anesth Analg. 2013 Nov;117(5):1093-100. doi: 10.1213/ANE.0b013e3182a705ae.
citation: Borkett KM, Riff DS, Schwartz HI, Winkle PJ, Pambianco DJ, Lees JP, Wilhelm-Ogunbiyi K. A Phase IIa, randomized, double-blind study of remimazolam (CNS 7056) versus midazolam for sedation in upper gastrointestinal endoscopy. Anesth Analg. 2015 Apr;120(4):771-80. doi: 10.1213/ANE.0000000000000548.
citation: Pambianco DJ, Borkett KM, Riff DS, Winkle PJ, Schwartz HI, Melson TI, Wilhelm-Ogunbiyi K. A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2016 May;83(5):984-92. doi: 10.1016/j.gie.2015.08.062. Epub 2015 Sep 9.
citation: Douglas K. Rex, MD, MACG, Raj Bhandari, MD, Taddese Desta MD, Michael DeMicco MD, Cynthia Schaeffer MD, Kyle Etzkorn, Charles Barish MD, Ronald Pruitt MD, Brooks Cash MD, FACG, Daniel Quirk MD, Felix Tiongco MD, David Bernstein MD, FACG. REMIMAZOLAM IS A SAFE AND EFFECTIVE AGENT FOR SEDATION IN OUTPATIENT COLONOSCOPY: RESULTS OF A PHASE 3, MULTICENTER, RANDOMIZED, PLACEBO CONTROLLED TRIAL. Program No. ACG 2016 Annual Scientific Meeting Abstracts. Las Vegas, NV: American College of Gastroenterology.
citation: Rex DK, Bhandari R, Desta T, DeMicco MP, Schaeffer C, Etzkorn K, Barish CF, Pruitt R, Cash BD, Quirk D, Tiongco F, Sullivan S, Bernstein D. A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy. Gastrointest Endosc. 2018 Sep;88(3):427-437.e6. doi: 10.1016/j.gie.2018.04.2351. Epub 2018 Apr 30.