Healthy
Conditions
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.
Interventions
DRUGHPG1860
6 subjects randomized to active compound and 2 subjects randomized to placebo
Sponsors
Hepagene (Shanghai) Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Part 1 SAD: 6 cohorts Part 2 MAD: 3 cohorts
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 AUCinf of HPG1860 | up to 48 hours | To assess the effect of food on a single dose of 20 mg HPG1860 by evaluating AUCinf |
| 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 |
| Vd | SAD: up to 48 hours; MAD: up to 14 days | Apparent volume of distribution |
| Cmax | SAD: up to 48 hours ; MAD: up to 14 days. | Maximum observed serum concentration |
Countries
United States
Outcome results
None listed