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

Sponsor

Sichuan Haisco Pharmaceutical Group Co., Ltd (Industry)

Overall Status

Completed

CT.gov ID

NCT04037657

Collaborator

(none)

Enrollment

Arms

6.7

Actual Duration (Months)

Study Details

Study Description

Brief Summary

This study was a single-center positive-controlled, randomized, dose-escalation study of HSK3486 in healthy female subjects administered as a single IV bolus dose.Subjects were confined to the study unit from the evening of Day -1 until the morning of Day 2, then were required to return for a follow up visit on Day 5. Intensive safety, PD and PK assessments were performed prior to dosing on Day 1 until 24 hours post-dose (Day 2).

Condition or Disease	Intervention/Treatment	Phase
Anesthesia Sedation	Drug: HSK3486 Drug: Propofol	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 1b, Positive-controlled, Dose-escalation Study to Determine the Safety, Pharmacodynamics and Pharmacokinetics of a Single Intravenous Dose of HSK3486 in Healthy Female Subjects.

Actual Study Start Date :

Apr 22, 2015

Actual Primary Completion Date :

Jun 9, 2015

Actual Study Completion Date :

Nov 13, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HSK3486 0.288 mg/kg ，0.432 mg/kg ，0.540 mg/kg ，0.648 mg/kg，0.810 mg/kg There were five cohorts of six subjects per cohort (5 HSK3486:1 propofol).	Drug: HSK3486 HSK3486 was administered as a single dose over a 1 minute infusion period. There were five cohorts of six subjects per cohort (5 HSK3486:1 propofol).
Active Comparator: Propofol 2.5 mg propofol	Drug: Propofol Propofol, at a dose of 2.5 mg/kg, was administered as a 1 minute infusion at a constant rate via infusion pump.

Arm

Intervention/Treatment

Experimental: HSK3486

0.288 mg/kg ，0.432 mg/kg ，0.540 mg/kg ，0.648 mg/kg，0.810 mg/kg There were five cohorts of six subjects per cohort (5 HSK3486:1 propofol).

Drug: HSK3486

HSK3486 was administered as a single dose over a 1 minute infusion period. There were five cohorts of six subjects per cohort (5 HSK3486:1 propofol).

Active Comparator: Propofol

2.5 mg propofol

Drug: Propofol

Propofol, at a dose of 2.5 mg/kg, was administered as a 1 minute infusion at a constant rate via infusion pump.

Outcome Measures

Primary Outcome Measures

Safety by measurement of Adverse Events [First dose of study drug on day 1]
Bispectral index （BIS） [From first dose of study drug until fully alert on day 1]
Modified observer's assessment of alertness/sedation（MOAA/S） [Time Frame: 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

Secondary Outcome Measures

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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 49 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female, aged 18 - 49 years (inclusive)
Women of child-bearing potential agreed to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy
Negative serum pregnancy test
In general good health without 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-CS findings on a physical examination, 12-lead Electrocardiogram (ECG) and vital signs (respiratory 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)
Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the 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 CONFIDENTIAL HSK3486 SAD_02 Sichuan Haisco Pharmaceutical Co., Ltd Version: 13 Nov 2015 Page 19 of 513
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 anti-inflammatory 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 PI and Sponsor.
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
CS (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
History of posture-related gastric reflux more than twice weekly
History of seizures or epilepsy
History of ischaemic heart disease
History of brady- or tachy-dysrhythmias requiring medical care
History of asthma, with bronchospasm requiring treatment in the last 3 months
Any condition, which in the Investigator's opinion, puts the subject at significant risk, could confound the study results or may interfere significantly with the subject's participation in the study.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Sichuan Haisco Pharmaceutical Group Co., Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sichuan Haisco Pharmaceutical Group Co., Ltd

ClinicalTrials.gov Identifier:

NCT04037657

Other Study ID Numbers:

HSK3486-Australian-02

First Posted:

Jul 30, 2019

Last Update Posted:

Jul 31, 2019

Last Verified:

Dec 1, 2015

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Propofol

Study Results

No Results Posted as of Jul 31, 2019