GLS4/RTV and TAF Drug-drug Interaction

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the drug-drug-interaction (DDI), pharmacokinetics (PK) and tolerability of GLS4/RTV combined with TAF in healthy subjects.

Detailed Description
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This is a 2-part study with each part is an open-label study in healthy adult subjects. Total 28 subjects will be enrolled into the study and divided into 2 part (Part A and Part B), 14 subjects in each part. With each part, the subject will be receive study drug per the defined treatment periods.

Official Title
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A Phase I, Single-center, Open Label Clinical Study, to Evaluate the Pharmacokinetic Character of GLS4 Combined With RTV or TAF Alone or GLS4 and RTV and TAF Combination Administration in Healthy Subjects

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: GLS4
* Drug: RTV
* Drug: TAF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, of any race, between 18 and 50 years of age, inclusive, at Screening; Body mass index between 18.0 and 28.0 kg/m2, inclusive, at Screening; Females of childbearing potential and male subjects will agree to use contraception from screening to the 6 months after the last administration. Exclusion Criteria: In the 12 months prior to screening, observing clinical significance of the following diseases, including but not limited to, gastrointestinal, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental, or cardio-cerebrovascular diseases; Allergic constitution (multiple drug and food allergies); A history of alcoholism; Take any prescription drug, over-the-counter drug, vitamin product or herbal medicine within 14 days of screening; Any drug that changes the liver enzyme activity, such as barbiturates and Rifampicin, was taken within 30 days before screening; P-GP, BCRP, OATP1B1, OATP1B3, OAT1, OAT3 or MRP4 inhibitors or inducers, such as azithromycin, pantoprazole or St. John's herb, etc., was taken within 30 days before screening; Female subjects are lactating or have positive blood pregnancy results during the screening period;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>Subjects will receive GLS4 and RTV on Day 1, TAF on Day 5-14, GLS4 and RTV and TAF on Day15. | Drug: GLS4<br>* It is a new dihydropyrimidine antiviral drug that interferes the assembly of HBV core granule.<br>Drug: RTV<br>* It is HIV protease inhibitors indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection; It is a CYP3A inhibitor combined with other drug to increase the exposure in human.<br>* Other names: ritonavir;Drug: TAF<br>* It is a hepatitis B virus (HBV) nucleoside analog reverse transcriptase inhibitor and is indicated for the treatment of chronic hepatitis B virus infection in adults with compensated liver disease.<br>* Other names: tenofovir alafenamide;|
| Experimental: Part B<br>Subjects will receive TAF on Day 1, GLS4 and RTV on Day 5-14, GLS4 and RTV and TAF on Day15. | Drug: GLS4<br>* It is a new dihydropyrimidine antiviral drug that interferes the assembly of HBV core granule.<br>Drug: RTV<br>* It is HIV protease inhibitors indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection; It is a CYP3A inhibitor combined with other drug to increase the exposure in human.<br>* Other names: ritonavir;Drug: TAF<br>* It is a hepatitis B virus (HBV) nucleoside analog reverse transcriptase inhibitor and is indicated for the treatment of chronic hepatitis B virus infection in adults with compensated liver disease.<br>* Other names: tenofovir alafenamide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | maximum observed plasma concentration | predose to 96 hour after dosing | 
| AUC | area under the plasma concentration-time curve (AUC) | predose to 96 hour after dosing | 
| Adverse event | To assess the safety and tolerability of therapy. | Baseline to day 22 |