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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized, Double-Blind, Placebo Controlled, Single and Multiple Ascending Doses (SAD/MAD) Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HPG1860

Conditions
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Healthy

Intervention / Treatment
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* Drug: HPG1860


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects aged 18-55 years old (inclusive), male or female Females must be of non-childbearing potential 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: 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 Taken an investigational drug within 3 months or 5 half-live, whichever is longer from the Screening date Any liver function panel analyte (LFT) value > upper limits of normal reference range 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1 SAD: 6 cohorts Part 2 MAD: 3 cohorts
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD 10mg<br>A single oral dose of 10 mg | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|
| Experimental: SAD 20mg<br>A single oral dose of 20 mg. Food effect will also be assessed at the same dose level. | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|
| Experimental: SAD 40mg<br>A single oral dose of 40mg | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|
| Experimental: SAD 80 mg<br>A single oral dose of 80 mg | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|
| Experimental: SAD 120 mg<br>A single oral dose of 120 mg | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|
| Experimental: SAD 150 mg<br>A single oral dose of 150 mg | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|
| Experimental: MAD 10mg<br>Dose regimen is once daily 10 mg for 14 consecutive days. | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|
| Experimental: MAD 30mg<br>Dose regimen is once daily 30 mg for 14 consecutive days. | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|
| Experimental: MAD 90 mg<br>Dose regimen is once daily 90mg for 14 consecutive days. | Drug: HPG1860<br>* 6 subjects randomized to active compound and 2 subjects randomized to placebo<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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