<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03758469</url>
  </required_header>
  <id_info>
    <org_study_id>HSK3486-103</org_study_id>
    <nct_id>NCT03758469</nct_id>
  </id_info>
  <brief_title>A Study Evaluating Drug-Drug Interaction (DDI) Between HSK3486 Injectable Emulsion and Rifampin Capsules</brief_title>
  <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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sichuan Haisco Pharmaceutical Group Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Haisco Pharmaceutical Group Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I, single-center, open-label, randomized,two-way crossover,&#xD;
      propofol-controlled, two-stage study evaluating the safety and&#xD;
      pharmacokinetics/pharmacodynamics of IV maintenance dose and IV single loade dose plus&#xD;
      maintenance dose of HSK3486 emulsion for injection in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 14, 2018</start_date>
  <completion_date type="Actual">March 10, 2019</completion_date>
  <primary_completion_date type="Actual">January 31, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Peak concentration (Cmax)</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve (AUC0-t, AUC0-∞)</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half life (t1/2)</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to fully awake</measure>
    <time_frame>From the start of HSK3486 administration until the subjects is fully awake on day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MOAA/S(modified observer's assessment of alert /sedation)-time curve</measure>
    <time_frame>From the start of HSK3486 administration until the subjects is fully awake on day 1</time_frame>
    <description>Observe the change of modified observer's assessment of alert /sedation during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BIS(bispectral index)-time curve</measure>
    <time_frame>From the start of HSK3486 administration to 60 min after the start of administration on day 1</time_frame>
    <description>Observe the changes of bispectral index during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Observe the changes of blood pressure during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Observe the changes of heart rate during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Respiratory rate or blood oxygen saturation</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Observe the changes of respiratory rate or blood oxygen saturation during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood routine test</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Observe the changes of blood routine test during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine routine test</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Observe the changes of urine routine test during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood biochemical examination</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Observe the changes of Blood biochemical examination during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-Electrocardiogram</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Observe the changes of heart rate, RR interval, QT interval , QTcF interval , PR interval and QRS interval of electrocardiogram during the whole trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Safety endpoits</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concurrent medications</measure>
    <time_frame>From the start of HSK3486 administration to 24 h after the start of administration on day 1</time_frame>
    <description>Safety endpoits</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Anesthesia</condition>
  <condition>Sedation</condition>
  <arm_group>
    <arm_group_label>HSK3486</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>0.4 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rifampin , HSK3486</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>600 mg;0.4 mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HSK3486</intervention_name>
    <description>Sequence 1: Intravenously infuse 0.4 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.</description>
    <arm_group_label>HSK3486</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rifampin , HSK3486</intervention_name>
    <description>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.</description>
    <arm_group_label>rifampin , HSK3486</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy males or females with full capacity for civil conduct, aged ≥18 and ≤45 years&#xD;
             old. Both male and female subjects should be enrolled;&#xD;
&#xD;
          2. Male subjects weighing ≥50 kg, female subjects weighing ≥45 kg. All subjects should&#xD;
             have a body mass index (BMI) of ≥19.0 and ≤26.0 kg/m2;&#xD;
&#xD;
          3. Blood pressure between 100-139/60-89 mmHg; heart rate between 60-99 beats/min; body&#xD;
             temperature between 35.8-37.5 °C; respiratory rate between 12-20 breaths/min; SpO2&#xD;
             when inhaling ≥95%;&#xD;
&#xD;
          4. Normal physical examinations, laboratory examinations (blood routine, blood&#xD;
             biochemistry and urine routine), and 12-lead electrocardiogram (ECG), or abnormal but&#xD;
             without clinical significance as judged by the investigators; no significantly&#xD;
             potential difficult airway (modified Mallampati score I-II);&#xD;
&#xD;
          5. No previous history of major organ primary diseases, such as liver, kidneys, digestive&#xD;
             tract, blood, and metabolic diseases; no history of malignant hyperthermia and other&#xD;
             genetic conditions; no history of mental/neurological diseases; no history of&#xD;
             epilepsy; no contraindications for deep sedation/general anesthesia; no clinically&#xD;
             significant history of anesthesia accidents;&#xD;
&#xD;
          6. Subjects must understand the procedures and methods of this study, and be willing to&#xD;
             provide informed consent and to complete the trial in strict accordance with trial&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known sensitivity to excipients in HSK3486 injectable emulsion (soybean oil, glycerin,&#xD;
             triglyceride, egg lecithin, sodium oleate and sodium hydroxide), rifampin, or&#xD;
             contraindications mentioned in the prescribing information of rifampin; history of&#xD;
             drug allergies (including anesthetics), allergic diseases, or those with hyperactive&#xD;
             immune response;&#xD;
&#xD;
          2. In receipt of any one of the following medications or treatments during&#xD;
             screening/baseline:&#xD;
&#xD;
               1. History of drug abuse or any signs of chronic benzodiazepines use (such as&#xD;
                  insomnia, anxiety, spasms) within 3 months prior to screening, or a positive&#xD;
                  urine drug test during baseline;&#xD;
&#xD;
               2. Participated in clinical trials involving any medications or medical devices&#xD;
                  within 3 months prior to screening, or subjects who have participated in 3 or&#xD;
                  more drug clinical trials within the past year;&#xD;
&#xD;
               3. In receipt of rifampin within 4 weeks prior to screening;&#xD;
&#xD;
               4. Serious infection, trauma or major surgery within 4 weeks prior to screening; or&#xD;
                  acute disease with clinical significance (determined by the investigator) within&#xD;
                  2 weeks prior to screening, including GI diseases or infections (such as&#xD;
                  respiratory or CNS infections);&#xD;
&#xD;
               5. In receipt of propofol, other sedatives/anesthetics and/or opioid analgesics or&#xD;
                  compounds containing analgesics within 1 week prior to baseline;&#xD;
&#xD;
               6. In receipt of prescription drugs, Chinese herbal medicines, over-the-counter&#xD;
                  drugs or food supplements (such as vitamins and calcium supplements) other than&#xD;
                  contraceptives, paracetamol, oral non-steroidal anti-inflammatory drugs, topical&#xD;
                  over-the-counter preparations, within 2 weeks prior to baseline; unless the&#xD;
                  principal investigator (PI) and the sponsor agree that the medication has no&#xD;
                  effect on the safety and PK/PD results of the trial;&#xD;
&#xD;
          3. A history or evidence of any one of the following diseases prior to&#xD;
             screening/baseline:&#xD;
&#xD;
               1. History of cardiovascular diseases such as: postural hypotension, severe&#xD;
                  arrhythmia, heart failure, Adams-Stokes syndrome, unstable angina, myocardial&#xD;
                  infarction within 6 months before screening, tachycardia/bradycardia requiring&#xD;
                  medication, third-degree atrioventricular block or QTcF interval ≥450 ms&#xD;
                  (Fridericia's correction formula);&#xD;
&#xD;
               2. Respiratory insufficiency, history of obstructive pulmonary disease, history of&#xD;
                  asthma, sleep apnea; history of failed tracheal intubation; history of&#xD;
                  bronchospasm requiring treatment within 3 months prior to screening; acute&#xD;
                  respiratory infection, and with obvious symptoms such as fever, wheezing, nasal&#xD;
                  congestion or cough within 1 week prior to baseline;&#xD;
&#xD;
               3. History of GI tract diseases: Gastrointestinal obstruction, active GI bleed,&#xD;
                  potential for reflux and aspiration;&#xD;
&#xD;
          4. Laboratory results that meet any of the following during screening/baseline:&#xD;
&#xD;
               1. Positive result for either HBsAg, HCV, HIV, or syphilis;&#xD;
&#xD;
               2. Abnormal hepatic or renal function confirmed after re-examination;&#xD;
&#xD;
                    -  ALT or AST &gt; 1×ULN;&#xD;
&#xD;
                    -  Creatinine &gt; 1×ULN;&#xD;
&#xD;
                    -  TBIL &gt; 1.0×ULN;&#xD;
&#xD;
          5. History of alcohol abuse within 3 months prior to screening, abuse defined as average&#xD;
             of &gt; 2 units of alcohol per day (1 unit = 360 mL beer or 45 mL liquor with 40% alcohol&#xD;
             or 150 mL wine), or positive result for breath alcohol test during baseline;&#xD;
&#xD;
          6. Smoke more than 5 cigarettes per day and a total of more than 60 cigarettes within 3&#xD;
             months prior to screening;&#xD;
&#xD;
          7. Blood donation or blood loss ≥200 mL within 30 days prior to screening; plasma&#xD;
             donation or plasma exchange within 7 days prior to screening;&#xD;
&#xD;
          8. Subjects who consume any beverages or foods containing alcohol, grapefruit juice or&#xD;
             methylxanthine (such as coffee, tea, coca-cola, chocolate, functional drinks), to&#xD;
             participate in strenuous physical activities and other factors that may affect drug&#xD;
             absorption, distribution, metabolism, and excretion within 2 days prior to enrollment;&#xD;
             subjects who are unable to fast for 8 hours prior to dose administration;&#xD;
&#xD;
          9. Subjects expected to have surgery or hospitalization during the trial;&#xD;
&#xD;
         10. Subjects unsuitable for arterial blood collection, such as subjects who have positive&#xD;
             Allen's test;&#xD;
&#xD;
         11. Women who are pregnant or breastfeeding; women of child-bearing potential or men who&#xD;
             are unwilling to use contraception during the trial; subjects who are planning&#xD;
             pregnancy within 1 month after the completion of the trial (including male subjects);&#xD;
&#xD;
         12. Subjects judged by the investigator to be unsuitable for participating in this trial&#xD;
             for any reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shanghai Public Health Clinical Center</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 25, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>August 19, 2019</last_update_submitted>
  <last_update_submitted_qc>August 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rifampin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03758469
org study id: HSK3486-103
nct id: NCT03758469
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Peak concentration (Cmax)
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
measure: Area under the concentration-time curve (AUC0-t, AUC0-∞)
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
measure: Terminal elimination half life (t1/2)
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
measure: Time to fully awake
time frame: From the start of HSK3486 administration until the subjects is fully awake on day 1
measure: MOAA/S(modified observer's assessment of alert /sedation)-time curve
time frame: From the start of HSK3486 administration until the subjects is fully awake on day 1
description: Observe the change of modified observer's assessment of alert /sedation during the whole trial
measure: BIS(bispectral index)-time curve
time frame: From the start of HSK3486 administration to 60 min after the start of administration on day 1
description: Observe the changes of bispectral index during the whole trial
measure: Blood pressure
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Observe the changes of blood pressure during the whole trial
measure: Heart rate
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Observe the changes of heart rate during the whole trial
measure: Respiratory rate or blood oxygen saturation
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Observe the changes of respiratory rate or blood oxygen saturation during the whole trial
measure: Blood routine test
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Observe the changes of blood routine test during the whole trial
measure: Urine routine test
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Observe the changes of urine routine test during the whole trial
measure: Blood biochemical examination
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Observe the changes of Blood biochemical examination during the whole trial
measure: 12-Electrocardiogram
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Observe the changes of heart rate, RR interval, QT interval , QTcF interval , PR interval and QRS interval of electrocardiogram during the whole trial
measure: Number of patients with adverse events
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Safety endpoits
measure: Concurrent medications
time frame: From the start of HSK3486 administration to 24 h after the start of administration on day 1
description: Safety endpoits
arm group label: HSK3486
arm group type: Experimental
description: 0.4 mg/kg
arm group label: rifampin , HSK3486
arm group type: Experimental
description: 600 mg;0.4 mg/kg
intervention type: Drug
intervention name: HSK3486
description: Sequence 1: Intravenously infuse 0.4 mg/kg HSK3486 in the morning on an empty stomach. Complete infusion within 1 min.
arm group label: HSK3486
intervention type: Drug
intervention name: rifampin , HSK3486
description: 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.
arm group label: rifampin , HSK3486
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: China
responsible party type: Sponsor
mesh term: Rifampin