The PK/PD Study of Single 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 single-dose study the investigators evaluated the safety, tolerablity and PK/PD profiles of SHR3824 in healthy subjects.

Official Title
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Pharmacokinetics, Pharmacodynamics, Safety and Tolerability Study Following Single 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 acception 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 1<br>SHR3824 2.5 mg/day or placebo. | Drug: SHR3824<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of SHR3824 taken for single dose.<br>* Other names: Henagliflozin;Drug: Placebo<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of Placebo taken for single dose.<br>|
| Experimental: Cohort 2<br>SHR3824 5 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. | Drug: SHR3824<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of SHR3824 taken for single dose.<br>* Other names: Henagliflozin;Drug: Placebo<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of Placebo taken for single dose.<br>|
| Experimental: Cohort 3<br>SHR3824 10 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. | Drug: SHR3824<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of SHR3824 taken for single dose.<br>* Other names: Henagliflozin;Drug: Placebo<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of Placebo taken for single dose.<br>|
| Experimental: Cohort 4<br>SHR3824 25 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. | Drug: SHR3824<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of SHR3824 taken for single dose.<br>* Other names: Henagliflozin;Drug: Placebo<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of Placebo taken for single dose.<br>|
| Experimental: Cohort 5<br>SHR3824 50 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. | Drug: SHR3824<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of SHR3824 taken for single dose.<br>* Other names: Henagliflozin;Drug: Placebo<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of Placebo taken for single dose.<br>|
| Experimental: Cohort 6<br>SHR3824 100 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. | Drug: SHR3824<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of SHR3824 taken for single dose.<br>* Other names: Henagliflozin;Drug: Placebo<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of Placebo taken for single dose.<br>|
| Experimental: Cohort 7<br>SHR3824 200 mg/day or placebo. The actual dose (mg) level selected for each cohort may be modified based on evaluation of preliminary safety, pharmacokinetic and pharmacodynamic data from previous cohorts. | Drug: SHR3824<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of SHR3824 taken for single dose.<br>* Other names: Henagliflozin;Drug: Placebo<br>* A tablet of 2.5 mg, 5 mg, 10 mg, 25 mg, 50mg, 100mg, 200 of Placebo taken for single dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total 24-hour urinary glucose excretion as a measure of pharmacodynamic effect. |  | 24h after dosing | 
| SHR3824 and its metabolites of concentrations to characterize SHR3824 harmacokinetics. |  | Up to 72h after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with adverse events as a measure of safety and tolerability |  | up to day 72h after dosing | 

 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