Clinical trial NCT04845646: DDI Study of ASC41 in HV and the PK, Safety and Tolerability in Subjects With NAFLD.
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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
NAFLD
Keywords: Healthy
NAFLD
DDI (Drug-Drug Interaction)
Itraconazole
Phenytoin
THR beta agonist
ASC41
Lead sponsor: Ascletis Pharma Inc
Sponsor class: INDUSTRY
First posted: 2021-04-15
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: AUC of ASC41
timeFrame: Up to 24 days
measure: Cmax of ASC41
timeFrame: Up to 24 days
Secondary outcomes:
measure: t1/2 of ASC41
timeFrame: Up to 24 days
measure: CL/F of ASC41
timeFrame: Up to 24 days
measure: Vd/F of ASC41
timeFrame: Up to 24 days
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Up to 24 days
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: ICON early Phase Services LLC
state: Texas
Study officials:
References: