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

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).

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.

Study Overview

• Status: Completed
• Conditions: Healthy; NAFLD
• Intervention / Treatment: Drug: ASC41; Drug: Itraconazole; Drug: Phenytoin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • ICON early Phase Services LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ASC41 + Itraconazole group; ASC41 5 mg po, One 5 mg ASC41 tablet on day 1 and 11.; Itraconazole oral capsule 200 mg po qd (2 capsules given 1x/day or 200 mg/day) on days 6-16.	Drug: ASC41; 5mg/tablet; Drug: Itraconazole; 200mg/capsule
Experimental: ASC41 + Phenytoin group; ASC41 5 mg po, One 5 mg ASC41 tablet on day 1 and 19.; Phenytoin oral capsule 300 mg (100 mg 3 x/day) on days 6-19.	Drug: ASC41; 5mg/tablet; Drug: Phenytoin; 300mg/capsule
Experimental: ASC41 group; (1) ASC41 5 mg po. One 5 mg ASC41 tablet on day 1.	Drug: ASC41; 5mg/tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of ASC41	Evaluate the Area under the plasma concentration versus time curve.	Up to 24 days
Cmax of ASC41	Evaluate the Peak Plasma Concentration.	Up to 24 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
t1/2 of ASC41	Evaluate the Terminal-Phase Half-Life.	Up to 24 days
CL/F of ASC41	Evaluate the Apparent Systemic Clearance.	Up to 24 days
Vd/F of ASC41	Evaluate the Apparent Volume of Distribution.	Up to 24 days

Collaborators and Investigators

• Sponsor: Gannex Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Actual): June 10, 2021
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: April 11, 2021
• First Submitted That Met QC Criteria: April 11, 2021
• First Posted (Actual): April 15, 2021

Study Record Updates

• Last Update Posted (Actual): July 19, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Healthy; NAFLD; Itraconazole; Phenytoin; DDI (Drug-Drug Interaction); ASC41; THR beta agonist
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Phenytoin
• Other Study ID Numbers: ASC41-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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