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

• ClinicalTrials.gov Identifier: NCT04033939
• Recruitment Status: Completed
• First Posted: July 26, 2019
• Last Update Posted: July 26, 2019
• Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd
• Information provided by (Responsible Party): Haisco Pharmaceutical Group Co., Ltd. ( Sichuan Haisco Pharmaceutical Group Co., Ltd )

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Anesthesia; Sedation	Drug: HSK3486; Drug: Propofol; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Following Screening, subjects who meet the inclusion/exclusion criteria will be assigned a subject number in the order in which they are enrolled in the study. The subject number will determine the allocation of treatment as per the randomization list which will be generated by INCResearch Australia Pty Ltd and provided to the pharmacist. Cohorts 1 and 2 are a placebo controlled design, with open-labelling for the sentinel subjects and double-blind thereafter. Cohorts 3 to 8 are an open-label, positive controlled design.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 13, 2014
• Actual Primary Completion Date: November 11, 2014
• Actual Study Completion Date: May 4, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety by measurement of Adverse Events [ Time Frame: First dose of study drug on day 1 ]

Secondary Outcome Measures :

1. Median effective dose (ED50) [ Time Frame: From first dose of study drug until fully alert on day 1 ]
2. Peak concentration (Cmax) [ Time Frame: From the start of administration to 48 hours after administration ]
3. Time to plasma peak concentration(Tmax) [ Time Frame: From the start of administration to 48 hours after administration ]
4. Terminal elimination half life (t1/2z) and mean residence time (MRT) [ Time Frame: From the start of administration to 48 hours after administration ]
5. Mean residence time (MRT) [ Time Frame: From the start of administration to 48 hours after administration ]
6. Area Under the Curve (AUC0-30min, AUC0-1h, AUC0-last, and AUC0-inf) [ Time Frame: From the start of administration to 48 hours after administration ]
7. Total clearance (CL) [ Time Frame: From the start of administration to 48 hours after administration ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 49 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Sichuan Haisco Pharmaceutical Group Co., Ltd
• ClinicalTrials.gov Identifier: NCT04033939
• Other Study ID Numbers: HSK3486Australia-01
• First Posted: July 26, 2019
• Last Update Posted: July 26, 2019
• Last Verified: June 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Propofol; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics