A Multiple-Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetic of HS-10383

Study Overview
=================
Brief Summary
-----------------
This study will investigate the safety, tolerability and pharmacokinetics of ascending multiple doses of HS-10383 in healthy subjects using a randomized, double blind, placebo controlled, single center study design.

Detailed Description
-----------------
HS-10383 is a selective P2X3 receptor antagonist being developed for the treatment of refractory/unexplained chronic cough. This Phase 1b study will investigate the safety, tolerability and pharmacokinetics of ascending multiple doses of HS-10383 administered orally to healthy subjects.

Official Title
-----------------
A Randomized, Double-Blind, Placebo Controlled, Phase Ib Study to Assess the Safety, Tolerability and Pharmacokinetics of Multiple-Dose Escalation HS-10383 in Healthy Adult Subjects

Conditions
-----------------
Cough

Intervention / Treatment
-----------------
* Drug: HS-10383
* Drug: HS-10383 Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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 sign the informed consent; Male weight ≥ 50kg, female weight ≥ 45kg, body mass index {BMI, BMI=weight/height 2 (kg/m2)} is controlled within the range of 18 26 (including the critical value); Exclusion Criteria: The following medical histories, such as neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal muscle system, metabolic endocrine system, skin disease, blood system, immune system and tumor, etc., were screened. evaluated as unsuitable to participate in this study; Any known presence or history of hypogeusia, abnormal taste or dysgeusia; Any known presence or history of severe allergies, or known to be allergic to the components of the test drug; Use of any drugs, including prescription drugs, over-the-counter drugs or herbal preparations, cannot be avoided or expected to start 2 weeks (or 5 half-lives) before screening and throughout the study period; Any findings of electrocardiogram outside from normal, such as the QT interval (QTcF) corrected by the Fridericia formula, the absolute value of QTcF for males is >450 ms, and the absolute value of QTcF for females is >470 ms; Any findings of blood pressure or pulse in resting state outside from normal a: 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
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HS-10383 (Multiple doses)<br>Escalating doses of HS-10383 administered orally once daily for a week in healthy participants. | Drug: HS-10383<br>* HS-10383 administered as one 50 mg, 150 mg, 300 mg and 450 mg capsule once daily, depending upon randomization.<br>* Other names: HS-10383 Tablets;|
| Placebo Comparator: HS-10383 Placebo (Multiple doses)<br>Escalating doses of HS-10383 Placebo administered orally daily for a week in healthy participants. | Drug: HS-10383 Placebo<br>* HS-10383 Placebo administered as one 50 mg, 150 mg, 300 mg and 450 mg capsule once daily, depending upon randomization.<br>* Other names: HS-10383 Placebo Tablets;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of treatment emergent adverse events | Safety and Tolerability Evaluation | up to 15 days | 
| Number of participants experiencing AE with abnormal laboratory values | Safety and Tolerability Evaluation | up to 15 days | 
| Number of participants experiencing AE with abnormal Electrocardiograph | Safety and Tolerability Evaluation | up to 15 days | 
| Safety and Tolerability Evaluation | Number of participants experiencing AE with abnormal vital sign | up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | To assess Cmax of Multiple ascending oral doses of HS-10383 | up to 192 hours after the last dose | 
| Area under the curve (AUC) | o assess AUC of Multiple ascending oral doses of HS-10383 | up to 192 hours after the last dose | 
| Time of Maximum Concentration (Tmax) | To assess Tmax of Multiple ascending oral doses of HS-10383 | up to 192 hours after the last dose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
RUCC, P2X3