A Phase Ⅰa Study of Remimazolam Tosylate in Healthy Volunteers

A Placebo- and Midazolam-Controlled, Phase Ia, Single Ascending-Dose Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Remimazolam Tosylate

The purpose of this study is to evaluate and compare the Pharmacokinetics/Pharmacodynamics and safety of Remimazolam Tosylate with midazolam in healthy volunteers

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: Remimazolam Tosylate

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100032
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy males or females
• Weight range 50 to 100 kg inclusive
• Body mass index (BMI) 18 to 26 kg/m2

Exclusion Criteria:

• Has a known sensitivity to benzodiazepines, flumazenil, or anesthetic agents, or a medical condition such that these agents are contraindicated
• With evidence of uncontrolled renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic dysfunction, in the opinion of the investigator or medical monitor
• Has known or suspected history of alcoholism or drug abuse or misuse within 6 months of Screening or evidence of tolerance or physical dependence before dosing with study drug
• With a history of laboratory results that show the presence of hepatitis B surface antigen (HBs Ag), hepatitis C antibody (HCV Ab), or human immunodeficiency virus (HIV)
• Pregnant,lactating
• Mallampati score ≥3

Study Plan

How is the study designed?

Design Details

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

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.01 mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 2.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.02 mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 3.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.05 mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 4.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.075 mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 5.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.1 mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 6.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.15 mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 7.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.2 mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 8.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.25 mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 9.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.3mg/kg body weight	Drug: Remimazolam Tosylate
Experimental: 10.Remimazolam Tosylate; Single IV bolus of Remimazolam Tosylate over 1 minute at 0.35 mg/kg body weight	Drug: Remimazolam Tosylate
Active Comparator: 11.Midazolam; Single IV bolus of Midazolam over 1 minute at 0.075 mg/kg body weight	Drug: Midazolam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To study the Pharmacokinetics of Remimazolam Tosylate by assessment of drug concentration through blood sample analysis	Pre-dose to 8 hours post-dosee
Bispectral index (BIS) and Modified Observer's Assessment of Alertness/Sedation(MOAA/S) score assessments	Pre-dose to 2 hours post-dose
Adverse event；Vital sign；Physical examination；Laboratory examination；ECG；The nervous system function test	Pre-dose to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Bei Hu, Professor, Peiking Union Medical College Hospital

Publications and helpful links

General Publications

• Chen X, Sang N, Song K, Zhong W, Wang H, Jiang J, Huang Y, Hu P. Psychomotor Recovery Following Remimazolam-induced Sedation and the Effectiveness of Flumazenil as an Antidote. Clin Ther. 2020 Apr;42(4):614-624. doi: 10.1016/j.clinthera.2020.02.006. Epub 2020 Mar 13.
• Zhou Y, Hu P, Huang Y, Nuoer S, Song K, Wang H, Wen J, Jiang J, Chen X. Population Pharmacokinetic/Pharmacodynamic Model-Guided Dosing Optimization of a Novel Sedative HR7056 in Chinese Healthy Subjects. Front Pharmacol. 2018 Nov 19;9:1316. doi: 10.3389/fphar.2018.01316. eCollection 2018. Erratum In: Front Pharmacol. 2019 Mar 19;10:251.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2013
• Primary Completion (Actual): June 20, 2014
• Study Completion (Actual): June 20, 2014

Study Registration Dates

• First Submitted: October 22, 2013
• First Submitted That Met QC Criteria: October 22, 2013
• First Posted (Estimate): October 25, 2013

Study Record Updates

• Last Update Posted (Actual): January 31, 2018
• Last Update Submitted That Met QC Criteria: January 30, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Health; Remimazolam Tosylate; Phase Ⅰ 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: RMZL-PIa