A Study Evaluating Drug-Drug Interaction (DDI) Between HSK3486 Injectable Emulsion and Rifampin Capsules
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HSK3486 0.4 mg/kg |
Drug: HSK3486
Sequence 1: Intravenously infuse 0.4 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.
|
| Experimental: rifampin , HSK3486 600 mg;0.4 mg/kg |
Drug: rifampin , HSK3486
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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Observe the change of modified observer's assessment of alert /sedation during the whole trial
- BIS(bispectral index)-time curve [From the start of HSK3486 administration to 60 min after the start of administration on day 1]
Observe the changes of bispectral index during the whole trial
- Blood pressure [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Observe the changes of blood pressure during the whole trial
- Heart rate [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Observe the changes of heart rate during the whole trial
- Respiratory rate or blood oxygen saturation [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Observe the changes of respiratory rate or blood oxygen saturation during the whole trial
- Blood routine test [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Observe the changes of blood routine test during the whole trial
- Urine routine test [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Observe the changes of urine routine test during the whole trial
- Blood biochemical examination [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Observe the changes of Blood biochemical examination during the whole trial
- 12-Electrocardiogram [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Observe the changes of heart rate, RR interval, QT interval , QTcF interval , PR interval and QRS interval of electrocardiogram during the whole trial
- Number of patients with adverse events [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Safety endpoits
- Concurrent medications [From the start of HSK3486 administration to 24 h after the start of administration on day 1]
Safety endpoits
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy males or females with full capacity for civil conduct, aged ≥18 and ≤45 years old. Both male and female subjects should be enrolled;
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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;
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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%;
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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);
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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;
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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.
Exclusion Criteria:
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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;
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In receipt of any one of the following medications or treatments during screening/baseline:
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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;
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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;
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In receipt of rifampin within 4 weeks prior to screening;
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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);
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In receipt of propofol, other sedatives/anesthetics and/or opioid analgesics or compounds containing analgesics within 1 week prior to baseline;
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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;
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A history or evidence of any one of the following diseases prior to screening/baseline:
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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);
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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;
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History of GI tract diseases: Gastrointestinal obstruction, active GI bleed, potential for reflux and aspiration;
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Laboratory results that meet any of the following during screening/baseline:
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Positive result for either HBsAg, HCV, HIV, or syphilis;
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Abnormal hepatic or renal function confirmed after re-examination;
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ALT or AST > 1×ULN;
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Creatinine > 1×ULN;
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TBIL > 1.0×ULN;
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History of alcohol abuse within 3 months prior to screening, abuse defined as average of > 2 units of alcohol per day (1 unit = 360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine), or positive result for breath alcohol test during baseline;
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Smoke more than 5 cigarettes per day and a total of more than 60 cigarettes within 3 months prior to screening;
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Blood donation or blood loss ≥200 mL within 30 days prior to screening; plasma donation or plasma exchange within 7 days prior to screening;
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Subjects who consume any beverages or foods containing alcohol, grapefruit juice or methylxanthine (such as coffee, tea, coca-cola, chocolate, functional drinks), to participate in strenuous physical activities and other factors that may affect drug absorption, distribution, metabolism, and excretion within 2 days prior to enrollment; subjects who are unable to fast for 8 hours prior to dose administration;
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Subjects expected to have surgery or hospitalization during the trial;
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Subjects unsuitable for arterial blood collection, such as subjects who have positive Allen's test;
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Women who are pregnant or breastfeeding; women of child-bearing potential or men who are unwilling to use contraception during the trial; subjects who are planning pregnancy within 1 month after the completion of the trial (including male subjects);
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Subjects judged by the investigator to be unsuitable for participating in this trial for any reason.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Shanghai Public Health Clinical Center | Shanghai | China |
Sponsors and Collaborators
- Sichuan Haisco Pharmaceutical Group Co., Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HSK3486-103