Clinical trial NCT03444480: A Phase Ⅰb Study of Remimazolam Tosylate in Healthy Volunteers
Official title: A Phase Ⅰb Study Evaluating the Pharmacokinetic,Safety and Efficacy of Remimazolam Tosylate in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anesthesia
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-02-23
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak Plasma Concentration (Cmax) of Remimazolam in human plasma.
timeFrame: From prior to study drug injection until 4 hours post-dose
measure: Area under the plasma concentration versus time curve (AUC) of Remimazolam in human plasma.
timeFrame: From prior to study drug injection until 4 hours post-dose
measure: Peak Plasma Concentration (Cmax) of M01 in human plasma.
timeFrame: From prior to study drug injection until 4 hours post-dose
measure: Area under the plasma concentration versus time curve (AUC) of M01 in human plasma.
timeFrame: From prior to study drug injection until 4 hours post-dose
Secondary outcomes:
measure: Safety by measurement of Adverse Events.
timeFrame: From start of study drug injection to patient discharge (approx. 2 days)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College
name: Pei Hu
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.