A Study Evaluating Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of HSK3486 Single Bolus Dose Followed With a 30 Minute Constant Infusion in Healthy Male Subjects

Phase 1

Completed

• Conditions: Anesthesia; Sedation
• Interventions: Drug: HSK3486

• Registration Number: NCT04029766
• Lead Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd

Brief Summary

This study was a single center, open-label, single dose escalation study in healthy male subjects to investigate a bolus dose followed by a 30 minute constant infusion of HSK3486 over two cohorts.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-11-10
• Primary Completion: 2015-12-14
• Study Completion: 2016-06-09
• Status Verified: 2019-06
• Study First Submitted: 2019-07-04
• Study First Submitted QC: 2019-07-20
• Study First Posted: 2019-07-23
• Last Update Submitted: 2021-01-26
• Last Update Posted: 2021-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 13

Inclusion Criteria

• 1. Male, aged 18 - 49 years (inclusive);
• 2. Be in general good health without clinically significant medical history;
• 3. American Society of Anesthesiologists (ASA) Physical Status Classification of I or II;
• 4. Body Mass Index (BMI) between 18 and 30 kg/m2 (inclusive);
• 5. Negative screen for drugs of abuse, alcohol, hepatitis B surface antigen (HBs-Ag), hepatitis C (HCVAb) and Human Immunodeficiency Virus (HIV) at Screening; and drugs of abuse, alcohol pre dose on Day -1
• 6. Normal or non-clinically significant findings on a physical examination, 12-lead electrocardiogram (ECG) and vital signs (respiration rate between 12 and 20 breaths per minute, blood pressure (BP) between 100-140/60-90 mmHg, heart rate between 50-99 beats per minute, temperature between 35.8°C and 37.5°C and pulse oximetry values > 95% on room air.);
• 7. Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the Investigator decided that out-of-range values were not clinically significant;
• 8. Ability to provide written informed consent;
• 9. Willing and able to follow study instructions and likely to complete all study requirements;
• 10. Suitable venous and arterial access.

Exclusion Criteria

• 1. History of allergy or sensitivity to: propofol, components of Fresofol 1% MCT/LCT propofol, or HSK3486 (excipients soy bean oil, glycerine, triglycerides, purified egg phospholipids, sodium oleate and sodium hydroxide), or plain lignocaine;
• 2. History of clinically significant problems with general anesthesia;
• 3. Current smoker, or a history of regular (more than weekly) use of tobacco- or nicotine-containing products within 2 months prior to Screening;
• 4. History of excessive alcohol intake (more than four standard drinks daily, on average) or use of recreational drugs within the last 3 months;
• 5. Use of prescription or over the counter medications within 7 days of Investigational Product administration, with the exception of contraceptive medications, paracetamol, oral non-steroidal antiinflammatory agents, topical over the counter preparations and routine vitamins (if they do not exceed an intake of 20 to 600 times the recommended daily dose), unless agreed as non-clinically relevant by the Principal Investigator and Sponsor;
• 6. Standard donation of blood within 30 days of the study;
• 7. Donation of plasma or participation in a plasmapheresis program within 7 days preceding this study;
• 8. Receipt of any investigational study drug within 30 days prior to Screening;
• 9. Unable to fast for the 6 hours prior to Investigational Product administration;
• 10. Clinically significant (as judged by the Investigator) presence of acute illness (e.g. gastrointestinal illness, infection such as influenza, upper respiratory tract infection) at admission to the clinical study unit;
• 11. Anticipated need for surgery or hospitalization during the study;
• 12. Anatomical abnormality that would potentially interfere with airway management under unconscious sedation or anesthesia;
• 13. History of posture-related gastric reflux more than twice weekly;
• 14. History of seizures or epilepsy ;
• 15. History of ischaemic heart disease;
• 16. History of brady- or tachy-dysrhythmias requiring medical care;
• 17. History of asthma, with bronchospasm requiring treatment in the last 3 months;
• 18. Any condition, which in the Investigator's opinion, put the subject at significant risk, could confound the study results or may interfere significantly with the subject's participation in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HSK3486	HSK3486	0.288 mg/kg bolus (1 min)+ 1 mg/kg/h constant infusion (30 min) or 0.540 mg/kg bolus (1 min)+ 2 mg/kg/h constant infusion (30 min)

Primary Outcome Measures

Name	Time	Method
Safety by measurement of Adverse Events	First dose of study drug on day 1

Secondary Outcome Measures

Name	Time	Method
Modified observer's assessment of alertness/sedation（MOAA/S）	From first dose of study drug until fully alert on day 1	Observe the change of modified observer's assessment of alert /sedation during the whole trial
Bispectral index （BIS）	From first dose of study drug until fully alert on day 1
Area Under the Curve (AUC0-30min, AUC0-1h, AUC0-last, and AUC0-inf)	From the start of administration to 48 hours after administration
Total clearance (CL)	From the start of administration to 48 hours after administration
Peak concentration (Cmax)	From the start of administration to 48 hours after administration
Terminal elimination half life (t1/2z) and mean residence time (MRT)	From the start of administration to 48 hours after administration
Median effective dose (ED50)	From first dose of study drug until fully alert on day 1
Mean residence time (MRT)	From the start of administration to 48 hours after administration
Time to plasma peak concentration(Tmax)	From the start of administration to 48 hours after administration