A Drug-drug Interaction (DDI) Study of Morphothiadine Mesilate/Ritonavir in Healthy Subjects

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 Morphothiadine Mesilate/Ritonavir combined with Entecavir or Tenofovir Disoproxil Fumarate in healthy subjects

Detailed Description
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This is a 2-part study with each part is an open-label, crossover study in healthy adult subjects. Total 56 subjects will be enrolled into the study and divided into 2 part (Part A and Part B), 28 subjects in each part. Part A is to evaluate the drug-interaction between GLS4/RTV and ETV, Part B is to evaluate the drug-interaction between GLS4/RTV and TDF. With each part, the subject will be split into two groups and receive study drug per the defined treatment periods of Day 1, Day 11-20 and Day 21.

Official Title
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A Open-label, Single Center Drug Interaction Study of Morphothiadine Mesilate/Ritonavir , Entecavir and Tenofovir Disoproxil Fumarate in Healthy Subjects

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: GLS4
* Drug: RTV
* Drug: ETV
* Drug: TDF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form before the trial and fully understand the contents of the trial, the process and possible adverse reactions Be able to complete the study according to the trail protocol Subjects (including partners) have no pregnancy plan within 1 year after the last dose of study drug and voluntarily take effective contraceptive measures Male subjects and must be 18 to 45 years of age inclusive Body weight ≥ 50 kg and body mass index（BMI）between 18 and 28 kg / m2, inclusive Physical examination and vital signs without clinically significant abnormalities. Exclusion Criteria: Use of >5 cigarettes per day during the past 3 months Known history of allergy to study drugs，or allergies constitution ( multiple drug and food allergies) History of alcohol abuse (14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits or 100 mL of wine) Donation or loss of blood over 450 mL within 3 months prior to screening 12-lead ECG with clinically significant Positive for Viral hepatitis (including hepatitis B and C), HIV and syphilis Subjects deemed unsuitable by the investigator 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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Male

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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A:Group A<br>Subjects will receive GLS4+RTV on Day 1,followed by ETV on Day11-21 and co-administration with GLS4+RTV on Day 21. | Drug: GLS4<br>* Administered GLS4 120 mg orally three times daily in fed state<br>* Other names: Morphothiadine Mesilate Capsules;Drug: RTV<br>* Administered RTV 100 mg orally three times daily in fed state<br>* Other names: Ritonavir tablet;Drug: ETV<br>* Administered orally ETV 0.5 mg once daily in fasted state<br>* Other names: Entecavir table;|
| Experimental: Part A:Group B<br>Subjects will receive ETV on Day 1,followed by GLS4+RTV on Day11-21 and co-administration with ETV on Day 21. | Drug: GLS4<br>* Administered GLS4 120 mg orally three times daily in fed state<br>* Other names: Morphothiadine Mesilate Capsules;Drug: RTV<br>* Administered RTV 100 mg orally three times daily in fed state<br>* Other names: Ritonavir tablet;Drug: ETV<br>* Administered orally ETV 0.5 mg once daily in fasted state<br>* Other names: Entecavir table;|
| Experimental: Part B:Group C<br>Subjects will receive GLS4+RTV on Day 1,followed by TDF on Day11-21 and co-administration with GLS4+RTV on Day 21. | Drug: GLS4<br>* Administered GLS4 120 mg orally three times daily in fed state<br>* Other names: Morphothiadine Mesilate Capsules;Drug: RTV<br>* Administered RTV 100 mg orally three times daily in fed state<br>* Other names: Ritonavir tablet;Drug: TDF<br>* Administered TDF 300 mg orally once daily in fasted state<br>* Other names: Tenofovir Disoproxil Fumarate table;|
| Experimental: Part B:Group D<br>Subjects will receive TDF on Day 1,followed by GLS4+RTV on Day11-21 and co-administration with TDF on Day 21. | Drug: GLS4<br>* Administered GLS4 120 mg orally three times daily in fed state<br>* Other names: Morphothiadine Mesilate Capsules;Drug: RTV<br>* Administered RTV 100 mg orally three times daily in fed state<br>* Other names: Ritonavir tablet;Drug: TDF<br>* Administered TDF 300 mg orally once daily in fasted state<br>* Other names: Tenofovir Disoproxil Fumarate table;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum plasma concentration of study drugs | Day 1-2 and Day 21-23 | 
| AUC | Area under the plasma concentration-time curve of study drugs | Day 1-2 and Day 21-23 | 
| Tmax | Time to maximum concentration of study drugs | Day 1-2 and Day 21-23 | 
| T1/2 | Terminal half-life of study drugs | Day 1-2 and Day 21-23 | 
| Adverse events | To assess the safety and tolerability after dosing | Baseline to day 23 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CL/F | Apparent clearance of study drugs | Day 1-2 and Day 21-23 | 
| Vz/F | Apparent volume of distribution of study drugs | Day 1-2 and Day 21-23 | 
| Cmin | Minimum plasma concentration of study drugs | Day 1-2 and Day 21-23 |