A Study Evaluating Safety, Pharmacodynamics and Pharmacokinetics of HSK3486 and Etomidate for Induction of Anesthesia in Healthy Male Subjects

NCT04054063 | Completed Phase 1

• 1 other identifier: HSK3486-Australian-04
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is designed as an open label, single dose combination of HSK3486 and etomidate in healthy adult male subjects. The study will evaluate the anesthetic/sedation effect of the combination of the 2 drugs and the safety profile including pain on injection, hypotension, tachycardia or bradycardia effects (HSK3486), and involuntary muscle movements, nausea and vomiting potential and adrenal suppression (etomidate). All subjects will be administered HSK3486 plus etomidate. Subjects will be confined to the study unit from the evening of Day -1 until the morning of Day 2, then will be required to return for a follow up visit on Day 7. Intensive PD, PK, safety and tolerability and assessments will be performed prior to dosing on Day 1 until 24 hours post-dose (Day 2).

Conditions

General Anesthetic; Sedation

Outcome Measures

Primary Outcomes (1)

• Safety by measurement of Adverse Events

  on day 1 until 24 hours post-dose

Secondary Outcomes (6)

• Richmond Agitation Sedation Scale (RASS)

  First dose of study drug on day 1

• bispectral index (BIS)

  First dose of study drug on day 1

• subject-rated Quality of Recovery Assessment (QoR-9）

  First dose of study drug on day 1

• Peak concentration (Cmax)

  on day 1 until 24 hours post-dose

• Time to plasma peak concentration(Tmax)

  on day 1 until 24 hours post-dose

Study Arms (1)

HSK3486+etomidate

EXPERIMENTAL

Cohort 1: HSK3486 0.324 mg/kg + etomidate 0.15 mg/kg Cohort 2: HSK3486 0.216 mg/kg + etomidate 0.2 mg/kg Cohort 3: HSK3486 0.432 mg/kg + etomidate 0.1 mg/kg There were an additional 2 cohorts (Cohorts 4 and 5) planned for dose escalation once the optimal ratio of the drug combination was identified from the first 3 cohorts. However, these 2 cohorts were not done as the results of Cohorts 1 to 3 suggested that dose increases would cause higher occurrence of drug-related adverse events (AEs).

Drug: HSK3486+ etomidate

Interventions

HSK3486+ etomidate DRUG

HSK3486+etomidate

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male, aged 18 - 49 years (inclusive)
• Be in general good health without clinically significant medical history, as determined by the investigator
• American Society of Anesthesiologists 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, hepatitis C and Human Immunodeficiency Virus (HIV) at screening; and drugs of abuse, alcohol pre dose on Day -1
• Normal or non-clinically significant findings on a physical examination, 12-lead ECG and vital signs (respiration rate between 12 and 20 breaths per minute, BP between 100-140/50-90 mmHg, heart rate between 45-99 beats per minute, temperature between 35.8 degrees and 37.5 degrees). Pulse oximetry values \>95% on room air.
• Clinical laboratory values within the normal limits as defined by the clinical laboratory, unless the investigator decides that out-of-range values are not clinically significant
• Ability 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, etomidate or components of HSK3486 (excipients soy bean oil, glycerine, triglycerides, purified egg phospholipids, sodium oleate and sodium hydroxide), or plain lignocaine
• History of clinically significant problems with anesthesia induction
• 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 4 standard drinks daily, on average) or use of recreational drugs within the last 3 months prior to screening
• Intake of \> 8 caffeine-containing drinks per day, on average, or approximately 800mg of caffenine daily on average; history of intolerance of abstinencce from caffeine for 3 days
• Use of prescription or over the counter medications within 7 days of investigational product administration, with the exception of paracetamol, oral non-steroidal anti-inflammatory agents, topical over the counter preparations and routine vitamins (if they do not exceed the recommended daily dose), unless agreed as non-clinically relevant by the investigator and sponsor.
• Standard donation of blood within 30 days of the study
• Donation of plasma or participation in a plasmapheresis program within 7 days of investigational product administration
• 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
• Craniofacial abnormality that would potentially interfere with airway management under unconscious sedation or anesthesia
• History of seizures or epilepsy
• History of ischaemic heart disease

Sponsors & Collaborators

• Sichuan Haisco Pharmaceutical Group Co., Ltd: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2019
• First Posted: August 13, 2019
• Study Start: November 30, 2016
• Primary Completion: December 21, 2016
• Study Completion: June 28, 2017
• Last Updated: August 13, 2019

Record last verified: 2017-06