A Phase Ⅰb Study of Remimazolam Tosylate in Healthy Volunteers

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

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

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

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Remimazolam Tosylate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remimazolam Tosylate 1<br>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<br>* Initial dose plus supplemental doses<br>* Other names: HR7056;|
| Experimental: Remimazolam Tosylate 2<br>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<br>* Initial dose plus supplemental doses<br>* Other names: HR7056;|

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Safety by measurement of Adverse Events. |  | From start of study drug injection to patient discharge (approx. 2 days) |