A Phase 1, Randomized, Placebo-controlled, Single & Multiple Dose Escalation Study to Investigate Safety, Pharmacokinetics, and Pharmacodynamics of SHR0534 in Healthy Chinese Volunteers
Overview
- Phase
- Phase 1
- Intervention
- SHR0534
- Conditions
- Healthy
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 51
- 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 & multiple dose escalation study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR0534. The study will be conducted with starting dose of 5 mg followed by dose escalation groups up to 100 mg. Healthy Chinese subjects will be randomized in each cohort to receive the study drug or placebo.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must have a BMI between 18 to 24.9 kg/m2, inclusive;
- •Clinical laboratory tests (i.e.blood chemistries, and urinalysis) must be within the normal reference range or clinically acceptable as determined by the investigator;
- •Subjects must be free of any clinically significant diseases based on medical history , physical examination and/or the investigator's judgment;
- •Winthout bad habits, including smoking, drinking and others;
- •Negative in Urine or serum pregnancy test for woman, female subject of childbearing potential and male subject must be willing to use an acceptable method of birth control for the duration of the study and continuing 90 days after discontinuing treatment with the investigational ;
- •Subject must be able to understand the information associated with the study, and are willing to provide written informed consent.
Exclusion Criteria
- •Clinically relevant abnormalities of physical examination, laboratory values, vital signs or ECG findings at the screening, as judged by the Investigator;
- •History of surgery or major trauma within 12 weeks of study entry, or surgery planned during the study;
- •History of hypersensitivity to SHR0534 or its components;
- •Any condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or a history of severe unconsciousness hypoglycemia judged by researchers;
- •History of liver disease. Those with Alanine aminotransferase (ALT) or Aspertate aminotransferase (AST)\>1.5 times upper limit of normal must be excluded;
- •Severe infection, trauma or major surgery 4 weeks before screening;
- •Congestive heart failure and other serious heart and lung diseases that need medication;
- •Have a positive test at Screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCVAb);
- •Positive in nicotine screening test, or cannot refrain from smoking;
- •Urine drug screen test positive for ethanol, cocaine, tetrahydrocannabinol (THC), barbiturates, amphetamines, benzodiazepines, or opiates;
Arms & Interventions
Pre-test
Three healthy male subjects were randomized in 2:1 ratio to receive single and then multiple (14 days) oral dose of 5 mg SHR0534 or matching placebo.
Intervention: SHR0534
Pre-test
Three healthy male subjects were randomized in 2:1 ratio to receive single and then multiple (14 days) oral dose of 5 mg SHR0534 or matching placebo.
Intervention: Placebo
Cohort 1
Eight healthy subjects were randomized in 3:1 ratio to receive single and then multiple (14 days) oral dose of 5 mg SHR0534 or matching placebo.
Intervention: SHR0534
Cohort 1
Eight healthy subjects were randomized in 3:1 ratio to receive single and then multiple (14 days) oral dose of 5 mg SHR0534 or matching placebo.
Intervention: Placebo
Cohort 2
Ten healthy subjects were randomized in 4:1 ratio to receive single and then multiple (14 days) oral dose of 10 mg SHR0534 or matching placebo.
Intervention: SHR0534
Cohort 2
Ten healthy subjects were randomized in 4:1 ratio to receive single and then multiple (14 days) oral dose of 10 mg SHR0534 or matching placebo.
Intervention: Placebo
Cohort 3
Ten healthy subjects were randomized in 4:1 ratio to receive single and then multiple (14 days) oral dose of 25 mg SHR0534 or matching placebo.
Intervention: SHR0534
Cohort 3
Ten healthy subjects were randomized in 4:1 ratio to receive single and then multiple (14 days) oral dose of 25 mg SHR0534 or matching placebo.
Intervention: Placebo
Cohort 4
Ten healthy subjects were randomized in 4:1 ratio to receive single and then multiple (14 days) oral dose of 50 mg SHR0534 or matching placebo.
Intervention: SHR0534
Cohort 4
Ten healthy subjects were randomized in 4:1 ratio to receive single and then multiple (14 days) oral dose of 50 mg SHR0534 or matching placebo.
Intervention: Placebo
Cohort 5
Ten healthy subjects were randomized in 4:1 ratio to receive single and then multiple (14 days) oral dose of 100 mg SHR0534 or matching placebo.
Intervention: SHR0534
Cohort 5
Ten healthy subjects were randomized in 4:1 ratio to receive single and then multiple (14 days) oral dose of 100 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 last treatment (Day 31)
Secondary Outcomes
- Area under the plasma or urine concentration curve after single or the last multiple oral dose (AUC)(From time 0 to 168 hours for single dose, and from time 0 to 192 hours after the last dose)
- Peak plasma concentration (Cmax) after single or the last multiple oral dose(From time 0 to 168 hours for single dose, and from time 0 to 192 hours after the last dose)
- Terminal elimination halflife (t½) for SHR0534 after single or the last multiple oral dose(From time 0 to 168 hours for single dose, and from time 0 to 192 hours after the last dose)
- Changes in the concentrations of blood glucose and insulin after single or multiple oral dose(From baseline up to 24 hours after last treatment (Day 24))