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

Colonoscopy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02290873
• Other study ID #: CNS7056-006
• Status: Completed
• Phase: Phase 3
• Start date: March 30, 2015
• Est. completion date: April 19, 2016

Study information

• Verified date: September 2020
• Source: Paion UK Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 461
• Est. completion date: April 19, 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Colonoscopy

Intervention

Drug:
• Remimazolam
For induction and maintenance of sedation
• Midazolam
For induction of maintenance and sedation
• Placebo
Inactive control arm

Locations

Country	Name	City	State
United States	Advanced Clinical Research Institute	Anaheim	California
United States	Gastroenterology Associates of Tidewater	Chesapeake	Virginia
United States	Precision Research Institute	Chula Vista	California
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Indiana University Health	Indianapolis	Indiana
United States	Borland-Grover Clinic, P.A	Jacksonville	Florida
United States	University of South Alabama	Mobile	Alabama
United States	Delta Research Partners Inc	Monroe	Louisiana
United States	Nashville Medical Research Institute	Nashville	Tennessee
United States	Thomas Jefferson Medical College	Philadelphia	Pennsylvania
United States	Wake Research Associates	Raleigh	North Carolina
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Precision Research Institute	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Paion UK Ltd.	Premier Research Group plc

Country where clinical trial is conducted

United States, 

References & 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. — View 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. — View 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

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. — View 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 — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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).