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

Anesthesia Clinical Trial

Official title:

A Single-Center, Open-Label, Randomized, Two-Stage, Two-Way Crossover Study Evaluating Drug-Drug Interaction (DDI) Between HSK3486 Injectable Emulsion and Rifampin Capsules in Healthy Subjects.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03758469
• Other study ID #: HSK3486-103
• Status: Completed
• Phase: Phase 1
• Start date: December 14, 2018
• Est. completion date: March 10, 2019

Study information

• Verified date: November 2018
• Source: Sichuan Haisco Pharmaceutical Group Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 10, 2019
• Est. primary completion date: January 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Healthy males or females with full capacity for civil conduct, aged =18 and =45 years old. Both male and female subjects should be enrolled;

2. 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;

3. 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%;

4. 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);

5. 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;

6. 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:

1. 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;

2. In receipt of any one of the following medications or treatments during screening/baseline:

1. 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;

2. 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;

3. In receipt of rifampin within 4 weeks prior to screening;

4. 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);

5. In receipt of propofol, other sedatives/anesthetics and/or opioid analgesics or compounds containing analgesics within 1 week prior to baseline;

6. 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;

3. A history or evidence of any one of the following diseases prior to screening/baseline:

1. 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);

2. 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;

3. History of GI tract diseases: Gastrointestinal obstruction, active GI bleed, potential for reflux and aspiration;

4. Laboratory results that meet any of the following during screening/baseline:

1. Positive result for either HBsAg, HCV, HIV, or syphilis;

2. Abnormal hepatic or renal function confirmed after re-examination;

• ALT or AST > 1×ULN;

• Creatinine > 1×ULN;

• TBIL > 1.0×ULN;

5. 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;

6. Smoke more than 5 cigarettes per day and a total of more than 60 cigarettes within 3 months prior to screening;

7. Blood donation or blood loss =200 mL within 30 days prior to screening; plasma donation or plasma exchange within 7 days prior to screening;

8. 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;

9. Subjects expected to have surgery or hospitalization during the trial;

10. Subjects unsuitable for arterial blood collection, such as subjects who have positive Allen's test;

11. 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);

12. Subjects judged by the investigator to be unsuitable for participating in this trial for any reason.

Related Conditions & MeSH terms

• Anesthesia
• Sedation

Intervention

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

Locations

Country	Name	City	State
China	Shanghai Public Health Clinical Center	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Sichuan Haisco Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak concentration (Cmax)		From the start of HSK3486 administration to 24 h after the start of administration on day 1
Primary	Area under the concentration-time curve (AUC0-t, AUC0-8)		From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Terminal elimination half life (t1/2)		From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Time to fully awake		From the start of HSK3486 administration until the subjects is fully awake on day 1
Secondary	MOAA/S(modified observer's assessment of alert /sedation)-time curve	Observe the change of modified observer's assessment of alert /sedation during the whole trial	From the start of HSK3486 administration until the subjects is fully awake on day 1
Secondary	BIS(bispectral index)-time curve	Observe the changes of bispectral index during the whole trial	From the start of HSK3486 administration to 60 min after the start of administration on day 1
Secondary	Blood pressure	Observe the changes of blood pressure during the whole trial	From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Heart rate	Observe the changes of heart rate during the whole trial	From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Respiratory rate or blood oxygen saturation	Observe the changes of respiratory rate or blood oxygen saturation during the whole trial	From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Blood routine test	Observe the changes of blood routine test during the whole trial	From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Urine routine test	Observe the changes of urine routine test during the whole trial	From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Blood biochemical examination	Observe the changes of Blood biochemical examination during the whole trial	From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	12-Electrocardiogram	Observe the changes of heart rate, RR interval, QT interval , QTcF interval , PR interval and QRS interval of electrocardiogram during the whole trial	From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Number of patients with adverse events	Safety endpoits	From the start of HSK3486 administration to 24 h after the start of administration on day 1
Secondary	Concurrent medications	Safety endpoits	From the start of HSK3486 administration to 24 h after the start of administration on day 1