Clinical trial NCT04037657: Evaluating the Safety, Pharmacodynamics and Pharmacokinetics of HSK3486 in Healthy Female Subjects.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anesthesia
Sedation
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-07-30
Enrollment: 25
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Safety by measurement of Adverse Events
timeFrame: First dose of study drug on day 1
measure: Bispectral index （BIS）
timeFrame: From first dose of study drug until fully alert on day 1
measure: Modified observer's assessment of alertness/sedation（MOAA/S）
timeFrame: Time Frame: From first dose of study drug until fully alert on day 1
Secondary outcomes:
measure: Median effective dose (ED50)
timeFrame: From first dose of study drug until fully alert on day 1
measure: Peak concentration (Cmax)
timeFrame: From the start of administration to 48 hours after administration
measure: Time to plasma peak concentration(Tmax)
timeFrame: From the start of administration to 48 hours after administration
measure: Area Under the Curve (AUC0-30min, AUC0-1h, AUC0-last, and AUC0-inf)
timeFrame: From the start of administration to 48 hours after administration
measure: Total clearance (CL)
timeFrame: From the start of administration to 48 hours after administration
Other outcomes:
Locations:
Study officials:
References: