Study to Assess the Safety, Tolerability and Pharmacokinetics of ZX-7101A and the Food Effect in Healthy Volunteers

Study Overview
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Brief Summary
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Randomized, double-blind and placebo-controled study to assess the safety, tolerability and pharmacokinetics of single ascending doses of ZX-7101A and its food effect in China healthy adult volunteers. The study is composed of 2 parts. Part 1 is to assess the safety, tolerability and pharmacokinetics of a single ascending doses of ZX-7101A tablet. Part 2 is to assess the food effect on ZX-7101A at a selected dose in a cross-over design.

Official Title
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Randomized, Double-blind and Placebo-controled Study to Assess the Safety, Tolerability and Pharmacokinetics of Single Ascending Doses of ZX-7101A and Its Food Effect in China Healthy Adult Volunteers

Conditions
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Tolerance, Safety Issues, Pharmacokinetics, Food Effect

Intervention / Treatment
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* Drug: ZX-7101A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults age of 18-45 years old BMI in the range of 9 26 kg/m2; Bodyweight (male) ≥50kg, Bodyweight (Female) ≥45kg In the judgement of the investigator, no clinically relevant abnormalities identified by a detailed medical history and full physical examination including BP and pulse rate measurement, or clinical laboratory tests Female subjects of nonchildbearing potential must be not pregnant or lactating. Subjects must consent and comply with the contraception requirement of the study. Able to understand the risks involved in the study, and provide written informed consent before the first study-specific procedure Able to understand and comply with the study procedures Exclusion Criteria: History of hypersensitivity or allergy to drug or food History of clinically significant abnormalities such as metabolic, liver, kidney, blood, lung, cardiovascular, gastrointestinal, urinary, endocrine, neurological, or psychiatric disorders; or in the judgement of the investigator, any medical abnormality that may be a concern to participate the study. Tympanic temperature >37.5℃, Pulse >100bmp or <50bmp, Systolic blood pressure ≥140mHg or ≤90mHg, or Diastolic blood pressure ≥90mHg or<50mHg Clinically relevant out-of-range baseline of total white cells or absolute neutrophil count Total bilirubin >1.5x ULN, AST >1.5 ULN or ALT >1.5ULN Estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 QTc interval > 450ms （ Fridericia's correction ， QTcF=QT/(RR^0.33) ）, QRS>120ms Acute respiratory tract infection within 2 weeks Any condition possibly affecting drug absorption, e.g. gastrectomy Received treatment of any prescription drug or alternative medicine within 4 weeks before first dosing or any nonprescription drug within 2 weeks or 5x half-life, whichever is longer Regular alcohol consumption >14units/week I the past 6 months or positive in alcohol breath test Use of tobacco or nicotine containing products more than the equivalent of 5 cigarettes per day within 3 months Unwilling or unable to restrict the intake of caffeine or alcohol within 72 hours before dosing or during the in-patient observation period Use or intake of any known liver enzyme inducer or inhibitor within 14 days History of drug abuse or positive urine drug test Positive test for Hepatitis C antibody (HCV), Hepatitis B surface antigen (HbsAg), Human immunodeficiency virus (HIV) antibody, or Syphilis antibody at Screening Accumulative blood donation >400ml within 3 months or >200ml within 4 weeks or planning to donate during the study Pregnancy or lactating at screening Having difficulty of drawing blood from vein Treatment with an investigational drug or procedure within 3 months Received vaccination within 3 months or plan to be received vaccine during the study Received any surgical procedure within 3 months at screening Any other reason that, in the opinion of the investigator, unlikely to comply with the clinical study protocol or is unsuitable for any other reason.

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: Sequential Assignment
Interventional Model Description: single ascending doses in part 1 and fasting/nonfasting crossover in part 2
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single dose of ZX-7101A treatment A<br>Administrated as a single oral dose in healthy subjects | Drug: ZX-7101A<br>* tablet<br>Drug: Placebo<br>* Tablet<br>|
| Experimental: Single dose of ZX-7101A treatment B<br>Administrated as a single oral dose in healthy subjects | Drug: ZX-7101A<br>* tablet<br>Drug: Placebo<br>* Tablet<br>|
| Experimental: Single dose of ZX-7101A treatment C<br>Administrated as a single oral dose in healthy subjects | Drug: ZX-7101A<br>* tablet<br>Drug: Placebo<br>* Tablet<br>|
| Experimental: Single dose of ZX-7101A treatment D<br>Administrated as a single oral dose in healthy subjects | Drug: ZX-7101A<br>* tablet<br>Drug: Placebo<br>* Tablet<br>|
| Experimental: Single dose of ZX-7101A treatment E<br>Administrated as a single oral dose in healthy subjects | Drug: ZX-7101A<br>* tablet<br>Drug: Placebo<br>* Tablet<br>|
| Experimental: ZX-7101A food effect<br>Administered as a selected, single oral dose of ZX-7101A in fasting state and non-fasting (with food) state. | Drug: ZX-7101A<br>* tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse effect (TEAEs) and severe adverse events (SAEs) | safety and tolerability | Day 1-day15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak plama concentration of ZX-7101A | To evaluate the maximum observed concentration (Cmax) after single oral dose of ZX-7101A | Days 1-15 | 
| Area under the plasma concentration of ZX-7101A | To evaluate the area under the curve (AUC) plasma-concentration after single oral dose of ZX-7101A | Days 1-15 | 
| Half-life of ZX-7101A | To evaluate the half-life of ZX-7101A after single oral dose of ZX-7101A | Days 1-15 | 
| Concentration of ZX-7101A in urine | To evaluate the concentration at a select treatment after single oral dose of ZX-7101A | Days 1-15 |