A Phase Ⅰb Study of Remimazolam Tosylate in Healthy Volunteers

A Phase Ⅰb Study Evaluating the Pharmacokinetic,Safety and Efficacy of Remimazolam Tosylate in Healthy Volunteers

The purpose of this study is to evaluate the Pharmacokinetics/Pharmacodynamics and safety of Remimazolam Tosylate in healthy volunteers after loading/maintenance dose regimen.

Study Overview

• Status: Completed
• Conditions: Anesthesia
• Intervention / Treatment: Drug: Remimazolam Tosylate

Detailed Description

1. Study the Pharmacokinetics/Pharmacodynamics of Remimazolam Tosylate in healthy volunteers after loading/maintenance dose regimen.
2. Study the reversal effect and time required of Flumazepine on Rimazolam'effect.
3. Study the Safety of Remimazolam Tosylate in healthy volunteers after loading/maintenance dose regimen.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, 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: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged ≥18 and ≤55 years.
• Weight range 50 to 100 kg and body mass index (BMI) 18 to 26 kg/m2.
• Willing and able to comply with the requirements of the protocol.
• Provide written informed consent to participate in the study.

Exclusion Criteria:

• Abnormal results of physical or laboratory examination with clinical significance
• 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).
• With evidence of uncontrolled renal, hepatic, central nervous system, respiratory, cardiovascular, or metabolic dysfunction, in the opinion of the investigator or medical monitor.
• Subject with clinically significant abnormalities in baseline 12-lead electrocardiogram (ECG) or vital signs（SBP <90 mmHg or >140 mmHg，DBP <50 mmHg or >90 mmHg；Hr <50 bpm or >100 bpm；SpO2 <95%）.
• Has a known sensitivity to benzodiazepines, flumazenil, or anesthetic agents, or a medical condition such that these agents are contraindicated.
• Receipt of other medication within 14 days of the first study day.
• Blood donation greater than 200 ml or participation in a clinical study of an unlicensed drug in the previous 3 months.
• History of smoking or alcohol abuse within 6 months of screening.
• History of grapefruit juice or any other foods affect the activity of cytochrome P450 3A4（CYP3A4） within 7 days of screening.
• Pregnant,lactating.
• Mallampati score ≥3.
• Patients who in the opinion of the investigator may not be able to comply with the requirements of the study are not eligible

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Remimazolam Tosylate 1; IV bolus of Remimazolam Tosylate with a loading dose of 0.4mg/kg body weight over 1 minute followed by a maintenance dose of 1.5mg/kg/h over 2 hours.1 h 55 min after dosing start， 0.5 mg Flumazenil is administered	Drug: Remimazolam Tosylate; Initial dose plus supplemental doses; Other Names: HR7056
Experimental: Remimazolam Tosylate 2; IV bolus of Remimazolam Tosylate with a loading dose of 0.4mg/kg body weight over 1 minute followed by a maintenance dose of 1.5mg/kg/h over 2 hours.1 h 55 min after dosing start time,0.5ml placebo is administered	Drug: Remimazolam Tosylate; Initial dose plus supplemental doses; Other Names: HR7056

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax) of Remimazolam in human plasma.		From prior to study drug injection until 4 hours post-dose
Area under the plasma concentration versus time curve (AUC) of Remimazolam in human plasma.		From prior to study drug injection until 4 hours post-dose
Peak Plasma Concentration (Cmax) of M01 in human plasma.	M01 is the main metabolite of Remimazolam	From prior to study drug injection until 4 hours post-dose
Area under the plasma concentration versus time curve (AUC) of M01 in human plasma.	M01 is the main metabolite of Remimazolam	From prior to study drug injection until 4 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety by measurement of Adverse Events.	From start of study drug injection to patient discharge (approx. 2 days)

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Pei Hu, Peking Union Medical College

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.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2014
• Primary Completion (Actual): August 16, 2014
• Study Completion (Actual): August 16, 2014

Study Registration Dates

• First Submitted: August 4, 2015
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): February 23, 2018

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: February 22, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: RMZL-PIb