Clinical trial NCT03751969: A Study Evaluating the Mass Balance of Micro-dose[14C]HSK3486 Emulsion Injection in Healthy Adults
Official title: A Study Evaluating the Mass Balance of Micro-dose [14C]HSK3486 Emulsion Injection in Healthy Chinese Male Adults
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Anesthesia
Sedation
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-11-23
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to evaluate the mass balance in healthy Chinese male subjects after receiving a single dose of intravenous \[14C\]HSK3486, so as to assess the overall pharmacokinetics and safety of HSK3486 in humans and provide a reference for reasonable use of this drug.


Eligibility criteria: Inclusion Criteria:

* Subjects enrolled in this study are required to meet all of the following:

  1. Healthy Chinese males aged 18-49 years old (inclusive);
  2. Body weight: body mass index (BMI) between 19-26 kg/m2 (inclusive); weight should be no less than 50 kg; weight difference between the lightest and the heaviest subjects enrolled should be no more than 10 kg;
  3. Vital signs: blood pressure between 90-140/60-90 mmHg; heart rate or pulse between 60-99 beats/min; body temperature (ear temperature) between 35.5-37.1 °C; respiratory rate between 12-24 breaths/min; blood oxygen saturation when inhaling ≥ 96% (inclusive);
  4. Normal major organ function, e.g. routine blood test, blood biochemistry, routine urinalysis, feces and fecal occult blood test, and blood coagulation are all normal, or abnormal with no clinical significance as judged by the investigators;
  5. Subjects who voluntarily sign the informed consent form, able to communicate well with the investigator and complete all trial procedures in accordance with the protocol.

Exclusion Criteria:

* Subjects who meet any of the following will be excluded:

  1. Subjects with clinically significant abnormalities during screening in physical examinations, laboratory tests, 12-lead ECG, chest X-ray or airway evaluation, including airway evaluation of a modified Mallampati score of IV; subjects with positive test result for hepatitis B surface antigen, hepatitis B e antigen, hepatitis C antibody, HIV antibody or syphilis antibody;
  2. Medication history: In receipt of any other investigational drug or participated in any drug or medical device clinical trial within 3 months before screening; or in receipt of propofol, other sedative/narcotic drugs and/or opioid analgesics or compounds containing analgesics within 72 hours prior to screening; or in receipt of any 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, and topical over-the-counter preparations within 2 weeks before screening; subjects can only be enrolled given the condition that the primary investigator (PI) and the sponsor agree that the drug used has no effect on the safety and mass balance results of the trial;
  3. Past and current medical history:

     A Subjects with a history of any severe disease, or concomitant diseases or abnormalities that may affect the test results as judged by the investigator, including but not limited to diseases or abnormalities in the circulatory system, endocrine system, neurological system, digestive system, urinary system, hematologic system, immune system, mental and metabolic aspects; B Subjects who have a past or current history of cardiovascular disease, including: heart failure, ischemic heart disease, long QT syndrome, arrhythmia requiring medication; a family history of Adams-Stokes syndrome or long QT syndrome; QTcF interval ≥ 450 ms (corrected by Fridericia's formula); C Subjects who have a past or current history of respiratory disease, including: obstructive pulmonary disease, asthma, or a history of bronchospasm requiring treatment within 3 months prior to screening; acute respiratory infections within 1 week prior to screening, with significant fever, wheezing, nasal congestion, and coughing.

     D Subjects who have a past or current history of gastrointestinal disease, including: gastroesophageal reflux, hemorrhoids or perianal disease with fecal blood, habitual constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease, etc.; E Subjects who have major surgery within 6 months before screening, or surgical incision not completely healed. Major surgery includes, but is not limited to any surgery that has a significant risk of bleeding, prolonged general anesthesia, incisional biopsy or significant traumatic injury; F Subjects with hyperactive immune response, including: sensitive to excipients of HSK3486 emulsion injections (soybean oil, glycerin, triglyceride, egg lecithin, sodium oleate and sodium hydroxide), history of drug allergies (including anesthetics), or other allergic diseases (such as allergic to any food ingredient or have special dietary requirements and cannot follow a uniform diet);
  4. Alcohol abuse or history of alcohol abuse within 3 months prior to screening, e.g. \> 14 units of alcohol consumption per week (1 unit = 360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine), or positive result for breath alcohol test at screening;
  5. Consumption of more than 5 cigarettes daily within 3 months before screening or habitual use of nicotine-containing products which cannot be withdrawn during the trial; history of respiratory irritation symptoms caused by smoking;
  6. Chronic drug abuse or use of soft drugs (such as marijuana) within 3 months before screening; or use of hard drugs (such as cocaine, amphetamines, phencyclidine) within 1 year before screening; or any signs of chronic benzodiazepines use (such as insomnia, anxiety) or positive urine drug test during screening;
  7. Habitual consumption of grapefruit juice or excessive tea, coffee and/or caffeinated beverages which cannot be withdrawn during the trial;
  8. Engaged in work requiring long-term exposure to radioactive conditions; or significant radioactive exposure within 1 year prior to the trial (≥ 2 chest/abdominal CT, or ≥ 3 other types of X-ray tests); or those who have participated in radiolabelling testing;
  9. Fertility planner during the trial period and within 1 year after the completion of the trial, or subjects or their spouses who refuse to take strict contraceptive measures (including taking condom, contraceptive sponge, contraceptive gel, diaphragm, intrauterine devices, oral or injectable contraceptives, subcutaneous implants, etc.) during the trial and within 1 year after the completion of the trial;
  10. Subjects who received blood transfusion within 1 month before screening or who had blood loss or blood donation ≥ 200 mL, or subjects who had plasma donation or plasma exchange within 7 days before the trial;
  11. Subject deemed unsuitable by the investigator for any other reason

Primary outcomes:
measure: Percentage of cumulative drug excretion of [14C]HSK3486 on biological specimens(urine and faeces) accounting for total radiation drug dose
timeFrame: from the start of administration to 96 hours after administration
measure: Maximum Plasma Concentration [Cmax] of 14C radioactivity and non-radiolabeled HSK3486 respectively
timeFrame: from the start of administration to 96 hours after administration
measure: Time to plasma peak concentration[Tmax] of 14C radioactivity and non-radiolabeled HSK3486 respectively
timeFrame: from the start of administration to 96 hours after administration
measure: Clearance half-life[t1/2] of 14C radioactivity and non-radiolabeled HSK3486 respectively
timeFrame: from the start of administration to 96 hours after administration
measure: Area Under the Curve [AUC] of 14C radioactivity and non-radiolabeled HSK3486 respectively
timeFrame: from the start of administration to 96 hours after administration
Secondary outcomes:
measure: Number of patients with adverse events and serious adverse events
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: Blood routine test
timeFrame: At the time of subject is being screened and at the end of study( nearly 96h after drug administration)
measure: Urine routine test
timeFrame: At the time of subject is being screened and at the end of study( nearly 96h after drug administration)
measure: Blood biochemical examination
timeFrame: At the time of subject is being screened and at the end of study( nearly 96h after drug administration)
measure: Blood pressure
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: Heart rate or pulse
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: Respiratory rate or blood oxygen saturation
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: Heart rate of electrocardiogram
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: RR interval of electrocardiogram
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: QT interval of electrocardiogram
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: QTcF interval of electrocardiogram
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: PR interval of electrocardiogram
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
measure: QRS interval of electrocardiogram
timeFrame: From the time the subject is being screened to the end of the trial( nearly 96h after drug administration)
Other outcomes:
Locations:
Study officials:
References: