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

NCT04037657 | Completed Phase 1

• 1 other identifier: HSK3486-Australian-02
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Anesthesia; Sedation

Outcome Measures

Primary Outcomes (3)

• 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）

  Observe the change of modified observer's assessment of alert /sedation during the whole trial

  Time Frame: From first dose of study drug until fully alert on day 1

Secondary Outcomes (5)

• 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

Study Arms (2)

HSK3486

EXPERIMENTAL

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

Propofol

ACTIVE COMPARATOR

2.5 mg propofol

Drug: Propofol

Interventions

HSK3486 DRUG

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).

HSK3486

Propofol DRUG

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

Propofol

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sichuan Haisco Pharmaceutical Group Co., Ltd: lead

MeSH Terms

Interventions

HSK3486; Propofol

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2019
• First Posted: July 30, 2019
• Study Start: April 22, 2015
• Primary Completion: June 9, 2015
• Study Completion: November 13, 2015
• Last Updated: July 31, 2019

Record last verified: 2015-12