A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Food Effect of SYHA1402 in Healthy Subjects

Study Overview
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Brief Summary
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A Multiple Doses Study to Evaluate the Safety, Tolerability, Pharmacokinetics (Including Food Effect) of SYHA1402 in Healthy Subjects.

Detailed Description
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This study consists of two parts: The objective of the food effect study (Part 1) is to investigate the effect of food on the pharmacokinetic profiles of SYHA1402 tablets under fed and fasted conditions following the oral administration of SYHA1402. The primary objective of the multiple doses study (Part 2) is to investigate safety, tolerability and Pharmacokinetics of SYHA1402 in healthy subjects following oral administration of Multiple rising doses. Secondary objectives are the exploration of pharmacokinetics (PK) following multiple oral doses.

Official Title
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Safety, Tolerability, Pharmacokinetics, and Food Effect of a Tablet Formulation of SYHA1402 in Healthy Subjects: A Phase-1, Single Center, Double-blind, Randomized, Placebo-controlled, Parallel-group Study

Conditions
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Diabetic Peripheral Neuropathy

Intervention / Treatment
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* Drug: FE-SYHA1402 100mg
* Drug: SYHA1402-25mg
* Drug: Placebo-25mg
* Drug: SYHA1402-50mg
* Drug: Placebo-50mg
* Drug: SYHA1402-150mg
* Drug: Placebo-150mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects aged 18 to 45 years (inclusive). Have a body mass index (BMI) between 19.0 and 26.0 kg/m2 inclusive and weigh at least 45.0 kg (female) or 50.0 kg (male) inclusive at screening. With no clinically significant or relevant abnormalities as determined by medical history, vital signs, physical examination, and clinical laboratory tests. All subjects of reproductive potential must agree to use effective, non-hormonal contraceptive measures (such as condoms, intrauterine devices without drugs) from the signing of informed consent to 3 months after the study. A subject is eligible to participate if she/he is not a person of childbearing potential (had a bilateral oophorectomy, bilateral salpingo-oophorectomy, or vasectomy). A male subject refrains from donating sperm during the study period and for 3 months after the study. Signed informed consent form. Exclusion Criteria: Female subjects who are pregnant or lactating. History or current evidence of any clinically significant cardiac, endocrinologic, hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic, psychiatric, renal, or other major disease, as determined by the investigator. Surgery history within six months before signing the informed consent; Allergic history to more than one drug or other serious allergic history. Any other abnormal findings on vital signs Any clinically significant abnormalities in ECG: a QTc interval greater than 450 ms (male) or 470 ms (female), or with a history of prolonged QTc interval; Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (anti-HCV), Human immunodeficiency virus antibody (anti-HIV) or Treponema Pallidum antibody (Anti-TP) at screening. Use of drugs within 2 weeks before signing the informed consent, including over-the-counter or prescription medication, including biological product, Chinese traditional medicine, herbal medicine, vitamin dietary supplements, health care products, oral or imbedded long-acting contraceptives. Alcohol abuse or positive test for alcohol screening. Smoker. History or clinical evidence of drug abuse within the one years before screening, or positive test for drug abuse at screening. Use of too much caffeine in beverages, foods or in any form, which may interfere the absorption, distribution, metabolism, or excretion of drugs, within 4 weeks before signing informed consent Loss of blood or blood donation more than 200 mL within 8 weeks before signing informed consent, or plan on blood donation during the study period and 1 months after the last dose of drug. Have a surgical schedule or a plan on excessive physical activity during the study period. Subjects participating in other clinical trials, or who have participated in any other clinical trials of drugs within three months before signing informed consent; Not suitable for this trial as determined by the investigator.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Food effect<br>Healthy subjects receive a single dose of SYHA1402 (100mg) in either a fasted state or with a meal. | Drug: FE-SYHA1402 100mg<br>* in either a fasted state or with a meal<br>|
| Experimental: Multiple doses 25mg<br>Healthy subjects receive multiple doses of SYHA1402 (25mg) or Placebo(25mg) for a total of 7 days (QD on Day1 and Day7, Q8h on Day2 to Day6）. | Drug: SYHA1402-25mg<br>* SYHA1402 25mg, oral tablets<br>Drug: Placebo-25mg<br>* Matching placebo tablets<br>|
| Experimental: Multiple doses 50mg<br>Healthy subjects receive multiple doses of SYHA1402 (50mg) or Placebo (50mg) for a total of 7 days (QD on Day1 and Day7, Q8h on Day2 to Day6）. | Drug: SYHA1402-50mg<br>* SYHA1402 50mg, oral tablets<br>Drug: Placebo-50mg<br>* Matching placebo tablets<br>|
| Experimental: Multiple doses 150mg<br>Healthy subjects receive multiple doses of SYHA1402 (150mg) or Placebo (150mg) for a total of 7 days (QD on Day1 and Day7, Q8h on Day2 to Day6）. | Drug: SYHA1402-150mg<br>* SYHA1402 150mg, oral tablets<br>Drug: Placebo-150mg<br>* Matching placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of food on the pharmacokinetic(Cmax） | Effect of food on the pharmacokinetic profile of SYHA1402 based on maximum observed plasma concentration (Cmax) (Part 1). | Predose and multiple timepoints up to 24 hours after the last dose in fed and fasted conditions | 
| Effect of food on the pharmacokinetic(AUC0-inf） | Effect of food on the pharmacokinetic profile of SYHA1402 based on AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to infinity) (Part 1). | Predose and multiple timepoints up to 24 hours after the last dose in fed and fasted conditions | 
| Effect of food on the pharmacokinetic(AUC0-t） | Effect of food on the pharmacokinetic profile of SYHA1402 based on AUC0-t (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to time of last measurable concentration) (Part 1). | Predose and multiple timepoints up to 24 hours after the last dose in fed and fasted conditions | 
| Safety and tolerability of multiple doses of SYHA1402 administered orally will be assessed (Part2). | incidence and severity of adverse events (AEs), abnormalities in clinical laboratory assessments, ECGs, vital sign assessments, and physical exams | up to 5 days after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SYHA1402 administered orally in fed and fasted conditions will be assessed (Part1) | incidence and severity of adverse events (AEs), abnormalities in clinical laboratory assessments, ECGs, vital sign assessments, and physical exams | up to 4 days after the last dose | 
| AUC0-t(Part2) | Rate and Extent of Absorption SYHA1402 by Assessment of the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point | Predose and multiple timepoints up to 24 hours after the last dose | 
| AUC0-inf(Part2) | Rate and Extent of Absorption SYHA1402 by Assessment of the area under the concentration-time curve of the analyte in plasma over the time interval from 0 to infinity | Predose and multiple timepoints up to 24 hours after the last dose | 
| Cmax(Part2) | Rate and Extent of Absorption SYHA1402 by Assessment of the maximum measured concentration of the analyte in plasma | Predose and multiple timepoints up to 24 hours after the last dose | 
| Tmax(Part2) | Rate and Extent of Absorption SYHA1402 by Assessment of the Time to Reach Maximum Observed Concentration | Predose and multiple timepoints up to 24 hours after the last dose | 
| t1/2z(Part2) | Rate and Extent of Absorption SYHA1402 by Assessment of the Apparent Terminal Elimination Half-life | Predose and multiple timepoints up to 24 hours after the last dose | 
| CL/F(Part2) | Rate and Extent of Absorption SYHA1402 by Assessment of the Apparent Clearance | Predose and multiple timepoints up to 24 hours after the last dose | 
| Vz/F(Part2) | Rate and Extent of Absorption SYHA1402 by Assessment of the Apparent Volume of Distribution | Predose and multiple timepoints up to 24 hours after the last dose | 
| Rac(AUC)(Part2) | Rate and Extent of Absorption of SYHA1402 by Assessment of the Accumulation Ratio | Predose and multiple timepoints up to 24 hours after the last dose | 
| Rac(Cmax) (Part2) | Rate and Extent of Absorption of AZD7986 by Assessment of the Accumulation Ratio for Cmax | Predose and multiple timepoints up to 24 hours after the last dose | 
| The assessment of the dose-proportionality based on Cmax (Part2) | The assessment of the dose-proportionality in the plasma pharmacokinetics (Cmax) of SYHA1402 | Predose and multiple timepoints up to 24 hours after the last dose | 
| The assessment of the dose-proportionality based on AUC (Part2) | The assessment of the dose-proportionality in the plasma pharmacokinetics (AUC) of SYHA1402 | Predose and multiple timepoints up to 24 hours after the last dose |