A Study Evaluating the Safety, Pharmacodynamics and Pharmacokinetics of HSK3486 in Healthy Subjects.

A Phase I, Placebo and Positive-controlled, Dose-escalation Study to Determine the Safety, Pharmacodynamics and Pharmacokinetics of a Single Intravenous Injection of HSK3486 in Healthy Subjects

This is the first clinical trial of HSK3486 and will be conducted in healthy volunteers to determine the safety, tolerability (including pain on injection), and PK(only to be assessed for subjects who are randomized to HSK3486 in Cohorts 3 to 8)and PD and profiles of HSK3486 administered as a single IV injection.

Results from this study will supports further clinical development of HSK3486. This study will be performed in compliance with the protocol, International Conference on Harmonization Good Clinical Practice (ICH GCP) and local regulatory requirements. Aspects of the study concerned with the investigational product will meet the requirements of Good Manufacturing Practice (GMP).

Study Overview

• Status: Completed
• Conditions: Anesthesia; Sedation
• Intervention / Treatment: Drug: Placebo; Drug: HSK3486; Drug: Propofol

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male, aged 18 - 49 years (inclusive).
• In general good health without clinically significant (CS) medical history.
• American Society of Anesthesiologists (ASA) Physical Status Classification of I or II.
• Body Mass Index (BMI) between 18 and 30 kg/m2 (inclusive).
• Negative screen for drugs of abuse, alcohol, Hepatitis B surface antigen (HBs-Ag), Hepatitis C Virus antibody (HCV-Ab) and Human Immunodeficiency Virus (HIV) at screening; and drugs of abuse, alcohol pre dose on Day -1.
• Normal or non-clinically significant (NCS) findings on a physical examination, 12-lead electrocardiogram (ECG) and vital signs (respiration rate between 12 and 20 breaths per minute, blood pressure 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).
• Clinical laboratory values within the normal limits as defined by the clinical laboratory samples, unless the Principal Investigator (PI) decided that out-of-range values were not CS.
• Able to provide written informed consent.
• Willing and able to follow study instructions and likely to complete all study requirements.
• Suitable venous and arterial access.

Exclusion Criteria:

• 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.
• History of CS problems with general anesthesia.
• Current smoker, or a history of regular (more than weekly) use of tobacco- or nicotine-containing products within 2 months prior to screening.
• History of excessive alcohol intake (more than four standard drinks daily, on average) or use of recreational drugs within the last 3 months.
• Use of prescription or over the counter medications within 7 days of Investigational Product administration, with the exception of simple analgesics such as paracetamol and oral non-steroidal antiinflammatory agents.
• Standard donation of blood within 30 days of the study.
• Donation of plasma or participation in a plasmapheresis program within 7 days preceding this study.
• Receipt of any investigational study drug within 30 days prior to screening.
• Unable to fast for the 6 hours prior to Investigational Product administration.
• 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.
• Anticipated need for surgery or hospitalization during the study.
• Anatomical abnormality that would potentially interfere with airway management under unconscious sedation or anesthesia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSK3486-01; Randomized to receive HSK3486 (0.016mg/kg,0.064mg/kg )as a single IV injection. HSK3486-01 was blinded.(2 HSK3486-01: 1 Placebo-01)	Drug: HSK3486
Placebo Comparator: Placebo-01; Randomized to receive placebo (0.016mg/kg,0.064mg/kg )as a single IV injection. placebo-01 was blinded.(2 HSK3486-01: 1 Placebo-01)	Drug: Placebo
Experimental: HSK3486-02; Randomized to receive either HSK3486（0.128mg/kg,0.192mg/kg,0.288mg/kg,0.432mg/kg,0.540mg/kg,0.648mg/kg,0.810mg/kg) as a single IV injection. HSK3486-02 was open-label.(5 HSK3486-02: 1 propofol-02)	Drug: HSK3486
Active Comparator: Propofol-02; Randomized to receive propofol (2.5mg/kg) as a single IV injection. Propofol-02 was open-label.(5 HSK3486-02: 1 propofol-02)	Drug: Propofol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety by measurement of Adverse Events	First dose of study drug on day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Median effective dose (ED50)	From first dose of study drug until fully alert on day 1
Peak concentration (Cmax)	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
Terminal elimination half life (t1/2z) and mean residence time (MRT)	From the start of administration to 48 hours after administration
Mean residence time (MRT)	From the start of administration to 48 hours after administration
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

Collaborators and Investigators

• Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2014
• Primary Completion (Actual): November 11, 2014
• Study Completion (Actual): May 4, 2015

Study Registration Dates

• First Submitted: July 4, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): July 26, 2019
• Last Update Submitted That Met QC Criteria: July 24, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: HSK3486Australia-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No