A Study Evaluating Drug-Drug Interaction (DDI) Between HSK3486 Injectable Emulsion and Rifampin Capsules

NCT03758469 | Completed Phase 1 DMC

• 1 other identifier: HSK3486-103
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I, single-center, open-label, randomized,two-way crossover, propofol-controlled, two-stage study evaluating the safety and pharmacokinetics/pharmacodynamics of IV maintenance dose and IV single loade dose plus maintenance dose of HSK3486 emulsion for injection in healthy subjects.

Conditions

Anesthesia; Sedation

Outcome Measures

Primary Outcomes (2)

• Peak concentration (Cmax)

  From the start of HSK3486 administration to 24 h after the start of administration on day 1

• Area under the concentration-time curve (AUC0-t, AUC0-∞)

  From the start of HSK3486 administration to 24 h after the start of administration on day 1

Secondary Outcomes (13)

• Terminal elimination half life (t1/2)

  From the start of HSK3486 administration to 24 h after the start of administration on day 1

• Time to fully awake

  From the start of HSK3486 administration until the subjects is fully awake on day 1

• MOAA/S(modified observer's assessment of alert /sedation)-time curve

  From the start of HSK3486 administration until the subjects is fully awake on day 1

• BIS(bispectral index)-time curve

  From the start of HSK3486 administration to 60 min after the start of administration on day 1

• Blood pressure

  From the start of HSK3486 administration to 24 h after the start of administration on day 1

Study Arms (2)

HSK3486

EXPERIMENTAL

0.4 mg/kg

Drug: HSK3486

rifampin , HSK3486

EXPERIMENTAL

600 mg;0.4 mg/kg

Drug: rifampin , HSK3486

Interventions

HSK3486 DRUG

Sequence 1: Intravenously infuse 0.4 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.

HSK3486

rifampin , HSK3486 DRUG

Sequence 2: Orally take 600 mg rifampin once a day for 8 consecutive days in the morning on an empty stomach, followed by 1 min intravenous infusion of 0.4 mg/kg HSK3486 30 min later.

rifampin , HSK3486

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or females with full capacity for civil conduct, aged ≥18 and ≤45 years old. Both male and female subjects should be enrolled;
• Male subjects weighing ≥50 kg, female subjects weighing ≥45 kg. All subjects should have a body mass index (BMI) of ≥19.0 and ≤26.0 kg/m2;
• Blood pressure between 100-139/60-89 mmHg; heart rate between 60-99 beats/min; body temperature between 35.8-37.5 °C; respiratory rate between 12-20 breaths/min; SpO2 when inhaling ≥95%;
• Normal physical examinations, laboratory examinations (blood routine, blood biochemistry and urine routine), and 12-lead electrocardiogram (ECG), or abnormal but without clinical significance as judged by the investigators; no significantly potential difficult airway (modified Mallampati score I-II);
• No previous history of major organ primary diseases, such as liver, kidneys, digestive tract, blood, and metabolic diseases; no history of malignant hyperthermia and other genetic conditions; no history of mental/neurological diseases; no history of epilepsy; no contraindications for deep sedation/general anesthesia; no clinically significant history of anesthesia accidents;
• Subjects must understand the procedures and methods of this study, and be willing to provide informed consent and to complete the trial in strict accordance with trial protocol.

You may not qualify if:

• Known sensitivity to excipients in HSK3486 injectable emulsion (soybean oil, glycerin, triglyceride, egg lecithin, sodium oleate and sodium hydroxide), rifampin, or contraindications mentioned in the prescribing information of rifampin; history of drug allergies (including anesthetics), allergic diseases, or those with hyperactive immune response;
• In receipt of any one of the following medications or treatments during screening/baseline:
• History of drug abuse or any signs of chronic benzodiazepines use (such as insomnia, anxiety, spasms) within 3 months prior to screening, or a positive urine drug test during baseline;
• Participated in clinical trials involving any medications or medical devices within 3 months prior to screening, or subjects who have participated in 3 or more drug clinical trials within the past year;
• In receipt of rifampin within 4 weeks prior to screening;
• Serious infection, trauma or major surgery within 4 weeks prior to screening; or acute disease with clinical significance (determined by the investigator) within 2 weeks prior to screening, including GI diseases or infections (such as respiratory or CNS infections);
• In receipt of propofol, other sedatives/anesthetics and/or opioid analgesics or compounds containing analgesics within 1 week prior to baseline;
• In receipt of prescription drugs, Chinese herbal medicines, over-the-counter drugs or food supplements (such as vitamins and calcium supplements) other than contraceptives, paracetamol, oral non-steroidal anti-inflammatory drugs, topical over-the-counter preparations, within 2 weeks prior to baseline; unless the principal investigator (PI) and the sponsor agree that the medication has no effect on the safety and PK/PD results of the trial;
• A history or evidence of any one of the following diseases prior to screening/baseline:
• History of cardiovascular diseases such as: postural hypotension, severe arrhythmia, heart failure, Adams-Stokes syndrome, unstable angina, myocardial infarction within 6 months before screening, tachycardia/bradycardia requiring medication, third-degree atrioventricular block or QTcF interval ≥450 ms (Fridericia's correction formula);
• Respiratory insufficiency, history of obstructive pulmonary disease, history of asthma, sleep apnea; history of failed tracheal intubation; history of bronchospasm requiring treatment within 3 months prior to screening; acute respiratory infection, and with obvious symptoms such as fever, wheezing, nasal congestion or cough within 1 week prior to baseline;
• History of GI tract diseases: Gastrointestinal obstruction, active GI bleed, potential for reflux and aspiration;
• Laboratory results that meet any of the following during screening/baseline:
• Positive result for either HBsAg, HCV, HIV, or syphilis;
• Abnormal hepatic or renal function confirmed after re-examination;

Sponsors & Collaborators

• Sichuan Haisco Pharmaceutical Group Co., Ltd: lead

Study Sites (1)

Shanghai Public Health Clinical Center

Shanghai, China

Location

MeSH Terms

Interventions

HSK3486; Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: November 25, 2018
• First Posted: November 29, 2018
• Study Start: December 14, 2018
• Primary Completion: January 31, 2019
• Study Completion: March 10, 2019
• Last Updated: August 20, 2019

Record last verified: 2018-11

Locations

CN (1)