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

NCT02290873 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CNS7056-006
• Study Type: interventional
• Target: 461
• Locations: 1 country
• Sites: 13

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.

Conditions

Colonoscopy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Time to Start of Procedure

  From first dose of study drug until insertion of the colonoscope

• Time to Fully Alert

  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

  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).

Study Arms (3)

Remimazolam

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Inactive control arm Fentanyl pre-treatment: 50 μg (or less for elderly/disabled subjects) and 25 μg top-up doses

Drug: Placebo

Midazolam

ACTIVE COMPARATOR

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

Interventions

Remimazolam DRUG

For induction and maintenance of sedation

Also known as: Byfavo, CNS7056

Remimazolam

Midazolam DRUG

For induction of maintenance and sedation

Also known as: Versed

Midazolam

Placebo DRUG

Inactive control arm

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Paion UK Ltd.: lead
• Premier Research: collaborator

Study Sites (13)

University of South Alabama

Mobile, Alabama, 36688, United States

Location

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

Precision Research Institute

Chula Vista, California, 91910, United States

Location

Precision Research Institute

San Diego, California, 92114, United States

Location

Borland-Grover Clinic, P.A

Jacksonville, Florida, 32256, United States

Location

Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Delta Research Partners Inc

Monroe, Louisiana, 71201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Thomas Jefferson Medical College

Philadelphia, Pennsylvania, 19107, United States

Location

Nashville Medical Research Institute

Nashville, Tennessee, 37205, United States

Location

Gastroenterology Associates of Tidewater

Chesapeake, Virginia, 23320, United States

Location

Related Publications (7)

• 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.

  PMID: 22190555 BACKGROUND

• 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.

  PMID: 22253270 BACKGROUND

• 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.

  PMID: 24108261 BACKGROUND

• 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.

  PMID: 25502841 BACKGROUND

• 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.

  PMID: 26363333 BACKGROUND

• 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.

  RESULT

• 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.

  PMID: 29723512 RESULT

MeSH Terms

Interventions

remimazolam; Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Trial Information
• Organization: PAION UK Ltd

reg_paion@paion.com

+49 2414453101

Study Officials

• Douglas K Rex, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2014
• First Posted: November 14, 2014
• Study Start: March 30, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 19, 2016
• Last Updated: October 20, 2020
• Results First Posted: November 9, 2018

Record last verified: 2020-09

Locations

US (13)