Study of Safety, Tolerability and PK, PD of HPG1860 in Healthy Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: HPG1860

• Registration Number: NCT04480697
• Lead Sponsor: Hepagene (Shanghai) Co., Ltd.

Brief Summary

This is a randomized, double-blind, placebo-controlled, single and multiple ascending dose Phase 1study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of HPG1860 orally administered in healthy subjects.

Detailed Description

In SAD and MAD studies, all subjects are randomized in a 3:1 ratio. In SAD study , there are 6 cohorts (8 subjects/cohort) with dose levels of 10mg, 20 mg, 40 mg, 80 mg, 120 mg and 150 mg respectively. Blood samples will be collected for safety, PK and PD assessments. After the completion of Cohort 2 (20 mg) in SAD study, following a 7-day washout period, the same 8 subjects will receive another single oral dose of 20 mg HPG1860 after a standard high fat/high calorie breakfast (the fed condition). PK blood samplings will be collected and Cmax and AUC will be used for assessing the food effect. In MAD study, there are 3 cohorts (8 subjects/cohort) with dose levels of 10mg, 30mg and 90 mg, respectively and dosing regimen is once daily for 14 consecutive days. Blood samples will be collected for safety, PK and PD assessments.

Study Timeline

• Study Start: 2019-09-23
• Study First Submitted: 2020-07-14
• Study First Submitted QC: 2020-07-17
• Study First Posted: 2020-07-21
• Primary Completion: 2020-11-25
• Study Completion: 2021-08-07
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-22
• Last Update Posted: 2022-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

1. Healthy subjects aged 18-55 years old (inclusive), male or female
2. Females must be of non-childbearing potential
3. Have a body mass index (BMI) between 18.0 and 32.0 kg/m2 (inclusive) and weigh at least 50 kg at time of Screening

Exclusion Criteria

1. Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator
2. Taken an investigational drug within 3 months or 5 half-live, whichever is longer from the Screening date
3. Any liver function panel analyte (LFT) value > upper limits of normal reference range
4. Positive blood screen for human immunodeficiency virus (HIV), hepatitis B core (IgG and IgM) and surface antigen (HBsAg), Hepatitis A antibody (IgM), hepatitis C antibody (IgG), or hepatitis E (IgG and IgM) at Screening
5. Any condition or finding that in the opinion of the Principal Investigator or designee would put the subject or study conduct at risk if the subject were to participate in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
MAD 30mg	HPG1860	Dose regimen is once daily 30 mg for 14 consecutive days.
MAD 90 mg	HPG1860	Dose regimen is once daily 90mg for 14 consecutive days.
SAD 20mg	HPG1860	A single oral dose of 20 mg. Food effect will also be assessed at the same dose level.
SAD 120 mg	HPG1860	A single oral dose of 120 mg
SAD 80 mg	HPG1860	A single oral dose of 80 mg
MAD 10mg	HPG1860	Dose regimen is once daily 10 mg for 14 consecutive days.
SAD 40mg	HPG1860	A single oral dose of 40mg
SAD 10mg	HPG1860	A single oral dose of 10 mg
SAD 150 mg	HPG1860	A single oral dose of 150 mg

Primary Outcome Measures

Name	Time	Method
After multiple ascending doses, number of subjects with treatment-emergent adverse events(TEAEs) in the HPG1860 dose-level cohorts	Day1-21	To investigate the safety and tolerability of orally administered MAD of HPG1860 by assessment of AEs, vital signs and clinical laboratory findings.
After single ascending doses, number of subjects with treatment-emergent adverse events(TEAEs) in the HPG1860 dose-level cohorts	Day1-8	To investigate the safety and tolerability of orally administered SAD of HPG1860 by assessment of AEs, vital signs and clinical laboratory findings.

Secondary Outcome Measures

Name	Time	Method
Effect of HPG1860 on Blood Concentration of FGF19 and 7-alpha-hydroxy-4-cholesten-3-one (C4)	SAD: Day 1. MAD: Day 1 and Day14	To assess blood FGF19 and C4 changes vs placebo after orally administered SAD and MAD of HPG1860
Cmax	SAD: up to 48 hours ; MAD: up to 14 days.	Maximum observed serum concentration
AUCinf	SAD: up to 48 hours ; MAD: up to 14 days.	Area under the curve from the time of dosing extrapolated to infinity
CL	SAD: up to 48 hours; MAD: up to 14 days	Apparent total body clearance of the drug from plasma
Tmax	SAD: up to 48 hours ; MAD: up to 14 days.	Time to reach Cmax
AUClast	SAD: up to 48 hours ; MAD: up to 14 days.	Area under the curve from the time of dosing to the time of the last measurable concentration
Vd	SAD: up to 48 hours; MAD: up to 14 days	Apparent volume of distribution
Effect of Food on Cmax of HPG1860	up to 48 hours	To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating Cmax
Effect of Food on AUC0-24h of HPG1860	24 hours	To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating AUC0-24h
Effect of Food on AUCinf of HPG1860	up to 48 hours	To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating AUCinf

Trial Locations

Locations (1)

Pharmaron CPC InC; 🇺🇸 Baltimore, Maryland, United States