DDI Study of ASC41 in HV and the PK, Safety and Tolerability in Subjects With NAFLD.

Healthy Clinical Trial

Official title:

Phase I Open Label, Drug-Drug Interaction, Study to Evaluate the Effect of Itraconazole and Phenytoin on the Pharmacokinetics of ASC41 in Healthy Volunteers and A Study to Evaluate the PK, Safety and Tolerability in Subjects With Non-alcoholic Fatty Liver Disease (NAFLD).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04845646
• Other study ID #: ASC41-105
• Status: Completed
• Phase: Phase 1
• Start date: March 16, 2021
• Est. completion date: June 10, 2021

Study information

• Verified date: March 2021
• Source: Gannex Pharma Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the effect of itraconazole, a strong inhibitor)of cytochrome P4503A , and phenytoin a strong inducer of cytochrome P450 3A, CYP3A4, CYP1A2 and CYP2C19 on the pharmacokinetics of ASC41, a THR beta agonist tables in healthy subjects. The PK, Safety and Tolerability of ASC 41 in Subjects with NAFLD will also be evaluated. Approximately 24 subjects including 16 healthy volunteers (HVs) and 8 subjects with NAFLD will be enrolled. This study consists of 3 cohorts.

Description:

This multiarm study in HVs and subjects with NAFLD is designed to further characterize the PK, safety and tolerability of ASC41. Part I of the study will assess the effect of itraconazole and phenytoin on the single-dose PK of ASC41 in HVs. Part II of the study will evaluate the PK, safety and tolerability of a single dose of ASC41 in subjects with NAFLD. The pharmacokinetics of ASC41 and its metabolite ASC41-A will be assessed in both parts I and II. The secondary objective of the study is to characterize the safety and tolerability of oral ASC41 in subjects in the U.S. with NAFLD and in HVs. Approximately 24 male and female participants will be enrolled. This study consists of 3 cohorts.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 10, 2021
• Est. primary completion date: June 10, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Key Inclusion Criteria:

• Part I Healthy subjects between 18 to 55 years of age
• Part II

1. Subjects with NAFLD

2. Subjects between 18 to 65 years of age

Key Exclusion criteria:

• Part I

1. A history of thyroid disease

2. A history of, or current liver disease, or liver injuries

3. Platelet count <150,000/mcL

4. INR> 1.2

5. History of, or current electrocardiogram (ECG) abnormalities, arrhythmias or heart valve diseases judged to be clinically significant by the investigator

• Part II

1. A history of thyroid disease

2. Current or history of cirrhosis or decompensated liver disease

3. AST or ALT > 5X ULN

4. DBIL > ULN

5. Acute or chronic liver disease other than NAFLD

6. A history of bariatric surgery

7. HbA1c >9.5% at screening

8. Testosterone or estrogen replacement therapy

9. Inducers or inhibitors of CYP3A4, including herbal therapies such as St John's Wort (CYP3A4 Inducer)

Related Conditions & MeSH terms

• Healthy
• NAFLD
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• ASC41
5mg/tablet
• Itraconazole
200mg/capsule
• Phenytoin
300mg/capsule

Locations

Country	Name	City	State
United States	ICON early Phase Services LLC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Gannex Pharma Co., Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC of ASC41	Evaluate the Area under the plasma concentration versus time curve.	Up to 24 days
Primary	Cmax of ASC41	Evaluate the Peak Plasma Concentration.	Up to 24 days
Secondary	t1/2 of ASC41	Evaluate the Terminal-Phase Half-Life.	Up to 24 days
Secondary	CL/F of ASC41	Evaluate the Apparent Systemic Clearance.	Up to 24 days
Secondary	Vd/F of ASC41	Evaluate the Apparent Volume of Distribution.	Up to 24 days
Secondary	Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Occurrence of Serious Adverse Event (SAE), Adverse Event (AE) resulting in treatment discontinuation and/or dose reductions, and AE of special interest, from baseline up to 24 days.	Up to 24 days