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

• Sponsor: Gannex Pharma Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04845646
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 3
• Actual Duration (Months): 2.8
• Patients Per Site Per Month: 8.5

Study Details

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

1. 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
• 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: Mar 16, 2021
• Actual Primary Completion Date: Jun 10, 2021
• Actual Study Completion Date: Jun 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 [Up to 24 days]

   Evaluate the Area under the plasma concentration versus time curve.

2. Cmax of ASC41 [Up to 24 days]

   Evaluate the Peak Plasma Concentration.

Secondary Outcome Measures

1. t1/2 of ASC41 [Up to 24 days]

   Evaluate the Terminal-Phase Half-Life.

2. CL/F of ASC41 [Up to 24 days]

   Evaluate the Apparent Systemic Clearance.

3. Vd/F of ASC41 [Up to 24 days]

   Evaluate the Apparent Volume of Distribution.

4. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [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

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

	Site	City	State	Country	Postal Code
1	ICON early Phase Services LLC	San Antonio	Texas	United States	78209

Sponsors and Collaborators

• Gannex Pharma Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gannex Pharma Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04845646
• Other Study ID Numbers: ASC41-105
• First Posted: Apr 15, 2021
• Last Update Posted: Jul 19, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• 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; Itraconazole; Phenytoin

Study Results

No Results Posted as of Jul 19, 2021