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

• ClinicalTrials.gov Identifier: NCT04845646
• Recruitment Status: Completed
• First Posted: April 15, 2021
• Last Update Posted: July 19, 2021
• Sponsor: Gannex Pharma Co., Ltd.
• Information provided by (Responsible Party): Gannex Pharma Co., Ltd.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Healthy; NAFLD	Drug: ASC41; Drug: Itraconazole; Drug: Phenytoin	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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).
• Actual Study Start Date: March 16, 2021
• Actual Primary Completion Date: June 10, 2021
• Actual Study Completion Date: June 10, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. AUC of ASC41 [ Time Frame: Up to 24 days ]
   Evaluate the Area under the plasma concentration versus time curve.
2. Cmax of ASC41 [ Time Frame: Up to 24 days ]
   Evaluate the Peak Plasma Concentration.

Secondary Outcome Measures :

1. t1/2 of ASC41 [ Time Frame: Up to 24 days ]
   Evaluate the Terminal-Phase Half-Life.
2. CL/F of ASC41 [ Time Frame: Up to 24 days ]
   Evaluate the Apparent Systemic Clearance.
3. Vd/F of ASC41 [ Time Frame: Up to 24 days ]
   Evaluate the Apparent Volume of Distribution.
4. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Up to 24 days ]
   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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, Texas

ICON early Phase Services LLC

San Antonio, Texas, United States, 78209

Sponsors and Collaborators

Gannex Pharma Co., Ltd.

More Information

• Responsible Party: Gannex Pharma Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04845646
• Other Study ID Numbers: ASC41-105
• First Posted: April 15, 2021
• Last Update Posted: July 19, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gannex Pharma Co., Ltd.:

Healthy; NAFLD; DDI (Drug-Drug Interaction); Itraconazole; Phenytoin; THR beta agonist; ASC41

Additional relevant MeSH terms:

Non-alcoholic Fatty Liver Disease; Fatty Liver; Liver Diseases; Digestive System Diseases; Itraconazole; Phenytoin; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP3A Inhibitors; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers