The PK/PD Study of Multiple Dose of SHR3824 in Healthy Volunteers

Study Overview
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Brief Summary
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SHR3824 is a novel inhibitor of renal sodium-glucose cotransporter 2, allows an insulin-independent approach to improve type 2 diabetes hyperglycemia. In this multiple-dose study the investigators evaluated the safety, tolerability and PK/PD profiles of SHR3824 in healthy subjects.

Official Title
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Pharmacokinetics, Pharmacodynamics, Safety and Tolerability Study Following Multiple Dose of SHR3824 in Healthy Subjects

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: SHR3824
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Chinese male and female subjects aged 18 to 45 years. BMI:18 -25 kg/m2. Healthy according to medical history, physical examination findings, 12-lead ECG findings, and clinical laboratory evaluations. Exclusion criteria: History of or current clinically significant medical illness as determined by the Investigator. History of clinically significant allergies, especially known hypersensitivity or intolerance to lactose. Pregnancy or breastfeeding . Significant acute or chronic medical illness, including renal impairment, or recent surgery. Donation of blood or plasma within the 4 weeks prior to the start of the study or acceptance of blood transfusion within 8 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort SHR3824/Placebo 1.25 mg<br>SHR3824 1.25 mg/day or placebo for 10 days. | Drug: SHR3824<br> <br> * Other names: Henagliflozin;Drug: Placebo<br> <br> |
| Experimental: Cohort SHR3824/Placebo 2.5 mg<br>SHR3824 2.5 mg/day or placebo for 10 days. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohort. | Drug: SHR3824<br> <br> * Other names: Henagliflozin;Drug: Placebo<br> <br> |
| Experimental: Cohort SHR3824/Placebo 5 mg<br>SHR3824 5 mg/day or placebo for 10 days. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohort. | Drug: SHR3824<br> <br> * Other names: Henagliflozin;Drug: Placebo<br> <br> |
| Experimental: Cohort SHR3824/Placebo 10 mg<br>SHR3824 10 mg/day or placebo for 10 days. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohort. | Drug: SHR3824<br> <br> * Other names: Henagliflozin;Drug: Placebo<br> <br> |
| Experimental: Cohort SHR3824/Placebo 25 mg<br>SHR3824 25 mg/day or placebo for 10 days. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohort. | Drug: SHR3824<br> <br> * Other names: Henagliflozin;Drug: Placebo<br> <br> |
| Experimental: Cohort SHR3824/Placebo 100mg<br>SHR3824 100 mg/day or placebo for 10 days. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohort. | Drug: SHR3824<br> <br> * Other names: Henagliflozin;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(Area under the curve) of SHR3824. |  | day1 and day11 to day 13. | 
| Cmax(the maximum concentration) of SHR3824. |  | day1 and day11 to day 13. | 
| Tmax(the time reaching maximum concentration) of SHR3824. |  | day1 and day11 to day 13. | 
| Halflife of SHR3824. |  | day1 and day11 to day 13. | 
| CL/F of SHR3824. |  | day1 and day11 to day 13. | 
| V/F of SHR3824. |  | day1 and day11 to day 13. | 
| Accumulation ratio of SHR3824 |  | Up to day 13. | 
| Urine glucose concentration of SHR3824. |  | day1 and day11 | 
| Plasma glucose concentration of SHR3824. |  | day1 and day11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, vital signs, physical exams , ECG, clinical labs |  | Days -14 to -1, 0, 13. | 
| Serum creatinine |  | Days -14 to -1, 0, 2, 9, 13. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHR3824 Type 2 diabetes mellitus SGLT2