Safety, Tolerance and Pharmacokinetics of THR-1442 in Chinese Healthy Subjects

Study Overview
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Brief Summary
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The purpose of this study was to investigate Safety, tolerability and pharmacokinetics in Chinese healthy subjects.

Detailed Description
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This was a single center, Phase 1, open-label SAD and MAD study designed to assess safety, tolerability and PK of orally administered THR-1442 tablets in Chinese healthy adults. Subjects were enrolled to receive 20mg THR-1442 tablet in Single dose group (20mg*1 day) and multiple dose group(20mg*7days). Blood samples for THR-1442 plasma concentrations were collected 0h till to 48hours.

Official Title
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Phase I Clinical Study to Evaluate the Safety, Tolerance and Pharmacokinetics of THR-1442 in Chinese Healthy Subjects

Conditions
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T2DM (Type 2 Diabetes Mellitus)

Intervention / Treatment
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* Drug: THR-1442 20mg Single dose
* Drug: THR-1442 20mg Multiple dose group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able to understand and be willing to sign informed consent and voluntarily participate in the study; Chinese women or men aged 18-45 (including 18 and 45) at the time of screening; Men or women who agree to effective contraception from the screening period until 30 days after the last dose in the trial; Agree to take at least one effective contraceptive measure; During screening and baseline, male weight ≥ 50.0kg, female weight ≥ 45.0kg, body mass index (BMI) in the range of 19   25.0kg/m2 (including 19 and 25.0kg/m2), [BMI = weight (kg) / height 2 (M2)]; Exclusion Criteria: According to the judgment of the site investigators, including clinical significant medical history in CNS, CV system, respiratory system, blood / hematopoietic system, gastrointestinal system, liver / kidney system，etc; Subjects with specific allergic history or allergic constitution such as drugs, food and pollen, or allergic to SGLT2 inhibitors or similar drugs; Alcoholics (drinking 14 units per week, each unit equivalent to 360mL beer or 150mL wine or 45mL alcohol of 40% alcohol), drug or drug dependence subjects; Smokers (smoking > 5 cigarettes per day or the same amount of other tobacco products); Subjects with a history of bladder dysfunction, such as urinary incontinence, frequent urination or nocturia; Blood donation within 3 months before screening, including component blood or massive blood loss (≥ 200ml), receiving blood transfusion or using blood products; Subjects who used prescription drugs, traditional Chinese medicine, over-the-counter drugs (OTC), vitamins, dietary supplements or supplements (e.g. ginseng) within 4 weeks before the first administration; From 7 days before the first dose to the whole study period, subjects who are unwilling or unable to guarantee to forbid by the following: no smoking, no alcohol, no caffeine containing products (including chocolate, tea, coffee, cola, etc.) and avoid strenuous exercise; Those who are unwilling or unable to guarantee to forbid pitaya, grapefruit, mango, carambola, fruit juice and spicy food containing the above fruits from 7 days before taking the medicine and the whole test period; The subject was unable to swallow the study drug or had gastrointestinal diseases leading to absorption disorders; Subjects who had participated in any drug or medical device clinical trial within 3 months before screening;

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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Study includes 2 parts: Single does part and multiple dose part. Single does part and multiple dose part are started same time.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: THR-1442 20mg Single dose group<br>THR-1442 20mg Single dose group: subject will be administrated 1 dose of 20mg THR-1442 on day1, the follow up till day 7. | Drug: THR-1442 20mg Single dose<br>* THR-1442 20mg is administrated 1 dose on Day 1, then follow till day 7.<br>|
| Experimental: THR-1442 20mg Multiple dose group<br>THR-1442 20mg Multiple dose group: subject will be administrated THR-1442 20mg QD on Day1-Day7, the follow up till day 14. | Drug: THR-1442 20mg Multiple dose group<br>* THR-1442 20mg is administrated QD for 7days, then follow till day 14.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collect and evaluate TEAEs (including clinical AEs and Lab AEs) of THR-1442 in healthy subjects during study | Collect data(TEAEs including clinical AEs and lab AEs) on Day7 and Day14 to evaluate THR1442 safety and tolerability | Single dose：Baseline to day 7 ； Multiple dose：Baseline to Day14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Select and evaluate pharmacokinetic characteristics(AUC) of THR-1442 in healthy subjects during the study | Collect blood samples on Single dose part and multiple dose part to evaluate THR1442 PK parameters （AUC） | Single dose：Day1-Day7； Multiple dose：Day1- Day14 | 
| Select and evaluate pharmacokinetic characteristics(Cmax) of THR-1442 in healthy subjects during the study | Collect blood samples on Single dose part and multiple dose part to evaluate THR1442 PK parameters （Cmax） | Single dose：Day1-Day7； Multiple dose：Day1- Day14 |