A PHASE I, RANDOMIZED, PLACEBO-CONTROLLED, SINGLE DOSE ESCALATION STUDY TO INVESTIGATE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF SHR0534 IN HEALTHY VOLUNTEERS
Overview
- Phase
- Phase 1
- Intervention
- SHR0534
- Conditions
- Healthy
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 40
- Primary Endpoint
- Number of treatment emergent adverse events (TEAEs)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This is a randomized, placebo-controlled, single dose escalation study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR0534. The study will be conducted with starting dose of 10 mg followed by dose escalation groups up to 200 mg. Eight subjects will be randomized in 3:1 ratio in each cohort to receive the study drug or placebo.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject must be adequately informed of the nature and risks of the study, able to understand the risks associated with the study, and are willing to provide written informed consent prior to screening.
- •Must have be at least 50 kg (110 lb), and a BMI between 19.0 to 32.0 kg/m2, inclusive.
- •Drug screen (including alcohol) must have been negative at Screening and on admission to study site.
- •Subjects must be free of any clinically significant diseases based on medical history , physical examination and/or the investigator's judgment
- •Clinical laboratory tests (i.e. CBC, platelet count, blood chemistries, and urinalysis) must be within the normal reference range or clinically acceptable as determined by the investigator.
- •Completion of the screening process within 14 days prior to dosing.
- •Must be able to communicate effectively with the study personnel.
- •Must be nonsmokers, defined as not having smoked tobacco or used chewing tobacco or nicotine-containing products in the 6 months prior to Day
- •Cotinine test must be negative at Screening and Day -
- •Must have, in the investigator's opinion, no clinically significant diseases or abnormal laboratory test values as determined by medical and psychiatric history, physical examination, or laboratory evaluations conducted at the screening visit or on clinic admission.
Exclusion Criteria
- •History of hypersensitivity to SHR0534 or its components.
- •History of or current clinically important systemic illnesses, including but not limited to cardiovascular, pulmonary, hepatobiliary, renal, hematological, gastrointestinal, endocrinological, immunological, dermatological, neurological, or psychiatric diseases, or any conditions that may place the subject at increased risk as determined by the investigator.
- •Any condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
- •History of surgery or major trauma within 12 weeks of study entry, or surgery planned during the study.
- •History of allergy or hypersensitivity to heparin, or heparin-induced thrombocytopenia.
- •History of myocardial infarction, stroke or sudden unexplained death in a first degree family member under the age of 60 years.
- •History of liver disease. Those with ALT or AST \>1.5 times upper limit of normal must be excluded.
- •Subjects with anemia or abnormal hematology parameters with clinically significance as determined by the investigator must be excluded.
- •History or presence of clinically significant electrocardiogram (ECG) abnormalities.
- •History of alcohol dependent, habitual heavy users of caffeinated beverages judged by the investigator.
Arms & Interventions
Cohort 2
Single oral dose of 25 mg SHR0534 or matching placebo
Intervention: SHR0534
Cohort 1
Single oral dose of 10 mg SHR0534 or matching placebo
Intervention: SHR0534
Cohort 1
Single oral dose of 10 mg SHR0534 or matching placebo
Intervention: Placebo
Cohort 2
Single oral dose of 25 mg SHR0534 or matching placebo
Intervention: Placebo
Cohort 3
Single oral dose of 50 mg SHR0534 or matching placebo
Intervention: SHR0534
Cohort 3
Single oral dose of 50 mg SHR0534 or matching placebo
Intervention: Placebo
Cohort 4
Single oral dose of 100 mg SHR0534 or matching placebo
Intervention: SHR0534
Cohort 4
Single oral dose of 100 mg SHR0534 or matching placebo
Intervention: Placebo
Cohort 5
Single oral dose of 200 mg SHR0534 or matching placebo
Intervention: SHR0534
Cohort 5
Single oral dose of 200 mg SHR0534 or matching placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Number of treatment emergent adverse events (TEAEs)
Time Frame: From baseline up to 8 days after single dose
Secondary Outcomes
- Changes in the concentrations of blood glucose after SHR0534 is orally administered(From baseline up to 8 hours after single dose)
- Area under the plasma concentration curve (AUC)(From time 0 to 168 hours after single dose)
- Peak plasma concentration (Cmax) after dose after dose(From time 0 to 168 hours after single dose)
- Terminal elimination halflife (t½) for SHR0534 after single dose after dose(From time 0 to 168 hours after single dose)