GLS4/RTV and TAF Drug-drug Interaction

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: GLS4; Drug: RTV; Drug: TAF

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • The First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part A; Subjects will receive GLS4 and RTV on Day 1, TAF on Day 5-14, GLS4 and RTV and TAF on Day15.	Drug: GLS4; It is a new dihydropyrimidine antiviral drug that interferes the assembly of HBV core granule.; Drug: RTV; 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.; Other Names: ritonavir; Drug: TAF; 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.; Other Names: tenofovir alafenamide
EXPERIMENTAL: Part B; Subjects will receive TAF on Day 1, GLS4 and RTV on Day 5-14, GLS4 and RTV and TAF on Day15.	Drug: GLS4; It is a new dihydropyrimidine antiviral drug that interferes the assembly of HBV core granule.; Drug: RTV; 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.; Other Names: ritonavir; Drug: TAF; 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.; Other Names: tenofovir alafenamide

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sunshine Lake Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2021
• Primary Completion (ACTUAL): March 12, 2021
• Study Completion (ACTUAL): March 12, 2021

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (ACTUAL): September 16, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 26, 2022
• Last Update Submitted That Met QC Criteria: May 20, 2022
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Ritonavir
• Other Study ID Numbers: PCD-DGLS4-20-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No