Phase 1a Study in Healthy Participants

Study Overview
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Brief Summary
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Oral HS-10506 in Chinese Healthy Subjects.

Detailed Description
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This is a phase 1a, first-in-human, double-blind, placebo-controlled clinical trial. The primary objective is to assess the safety, tolerability and pharmacokinetic of single dose HS-10506 in healthy subjects. The secondary objective is to observed pharmacokinetic parameters and metabolites after single dose of HS-10506.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of HS-10506 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: HS-10506
* Drug: HS-10506 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants aged from 18 to 45 years Subjects need to fully understand the research content and process, as well as possible adverse reactions, and voluntarily signed Informed Consent Form Males' weight ≥ 50kg, females' weight ≥ 45kg, body mass index {BMI, BMI=weight/height 2 (kg/m2)} is controlled within the range of 18 28 (including the critical value) During the study and for 3 months after receiving the last dose of study drug, subjects must agree not to donate sperm or eggs, not to plan to have children, and to use an effective method of contraception Exclusion Criteria: Has a history of chronic or serious disease from neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal muscle system, metabolic endocrine system, skin disease, blood system, immune system or tumor Has taken any drugs, including prescription drugs, over-the-counter drugs, herbal preparations, some health products or inhibitor/inducer of CYP3A4 or CYP3A5, within 2 weeks (or 5 half-lives) before screening and throughout the study period Has clinically significant ECG abnormalities, such as QT interval corrected according to Fridericia formula(QTcF), >450 ms (males), >470 ms (females) Has current manifestation of blood pressure or pulse abnormalities in resting state: such as systolic blood pressure <90 mmHg or ≥140 mmHg, diastolic blood pressure <60 mmHg or ≥90 mmHg, pulse <55 bpm or >100 bpm

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-10506<br>Healthy participants will be enrolled in dose escalation cohorts. Healthy participants will be receive either HS-10506 or matching placebo on Day 1. | Drug: HS-10506<br>* HS-10506 will be administered orally once on Day 1.<br>|
| Experimental: HS-10506 Placebo<br>Healthy participants will be enrolled in dose escalation cohorts. Healthy participants will be receive either HS-10506 or matching placebo on Day 1. | Drug: HS-10506 Placebo<br>* Matching placebo will be administered orally once on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and adverse events leading to discontinuation from the study, and their correlation with the investigational drug | The definition of adverse event [AE] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The definition of serious adverse event [SAE] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. | Screening until Trail phase (up to 5 weeks) | 
| Number of participants with clinically significant change from baseline in vital signs |  | From baseline to Day 3 | 
| Number of participants with clinically significant abnormalities in physical examination |  | From baseline to Day 3 | 
| Changes in 12-lead electrocardiogram from before to after dosing | Descriptive statistics of heart rate, PR interval, QT interval, and QTcF for observed values and changes from baseline will be summarized at each scheduled time point. | From baseline to Day 3 | 
| Change in Stanford Sleepiness Scale score from before to after dosing | Stanford Sleepiness Scale（SSS） is a simple and accurate method used to assess sleepiness symptom. Respondents use the scale from 1 to 7 to indicate their current level of sleepiness. Higher scores mean a higher level of sleepiness. Descriptive statistics of SSS scores and changes from baseline will be summarized at each scheduled time point. | From baseline to 4 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed maximum plasma concentration (Cmax) | Cmax will be obtained following administration of a single oral dose of HS-10506. | up to 48 hours after dosing | 
| Time to reach maximum plasma concentration (Tmax) | Tmax will be obtained following administration of a single oral dose of HS-10506. | up to 48 hours after dosing | 
| Area under the concentration-time curve from time zero to last time of quantifiable concentration（AUC0-t） | Area under the concentration-time curve from time zero to last time of quantifiable concentration（AUC0-t）will be obtained following administration of a single oral dose of HS-10506. | up to 48 hours after dosing | 
| Area under the concentration-time curve from time zero to infinity（AUC0-∞） | AUC0-t will be obtained following administration of a single oral dose of HS-10506. | up to 48 hours after dosing | 
| Terminal Rate Constant（λz） | Terminal Rate Constant（λz） will be obtained following administration of a single oral dose of HS-10506. | up to 48 hours after dosing | 
| Elimination Halflife (T1/2) | Elimination Halflife (T1/2) is the time measured for the concentration to decrease by one half，which will be obtained following administration of a single oral dose of HS-10506. | up to 48 hours after dosing | 
| Apparent clearance（CL/F） | CL/F will be obtained following administration of a single oral dose of HS-10506. | up to 48 hours after dosing | 
| Apparent Volume of Distribution（Vd/F） | Vd/F will be obtained following administration of a single oral dose of HS-10506. Time Frame: up to 48 hours after dosing | up to 48 hours after dosing | 
| Mean Residence Time(MRT) | RT will be obtained following administration of a single oral dose of HS-10506. | up to 48 hours after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HS-10506, Phase 1, Healthy