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

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

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

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sunshine Lake Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2018
• Primary Completion (Actual): July 31, 2018
• Study Completion (Actual): June 10, 2019

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 7, 2018

Study Record Updates

• Last Update Posted (Actual): October 9, 2019
• Last Update Submitted That Met QC Criteria: October 8, 2019
• Last Verified: September 1, 2018

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; Entecavir; Ritonavir
• Other Study ID Numbers: PCD-DGLS4-18-001

Drug and device information, study documents

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