Clinical trial NCT04480697: Study of Safety, Tolerability and PK, PD of HPG1860 in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Hepagene (Shanghai) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-07-21
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1 SAD: 6 cohorts Part 2 MAD: 3 cohorts
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: After single ascending doses, number of subjects with treatment-emergent adverse events(TEAEs) in the HPG1860 dose-level cohorts
timeFrame: Day1-8
measure: After multiple ascending doses, number of subjects with treatment-emergent adverse events(TEAEs) in the HPG1860 dose-level cohorts
timeFrame: Day1-21
Secondary outcomes:
measure: Effect of HPG1860 on Blood Concentration of FGF19 and 7-alpha-hydroxy-4-cholesten-3-one (C4)
timeFrame: SAD: Day 1. MAD: Day 1 and Day14
measure: Cmax
timeFrame: SAD: up to 48 hours ; MAD: up to 14 days.
measure: Tmax
timeFrame: SAD: up to 48 hours ; MAD: up to 14 days.
measure: AUClast
timeFrame: SAD: up to 48 hours ; MAD: up to 14 days.
measure: AUCinf
timeFrame: SAD: up to 48 hours ; MAD: up to 14 days.
measure: CL
timeFrame: SAD: up to 48 hours; MAD: up to 14 days
measure: Vd
timeFrame: SAD: up to 48 hours; MAD: up to 14 days
measure: Effect of Food on Cmax of HPG1860
timeFrame: up to 48 hours
measure: Effect of Food on AUCinf of HPG1860
timeFrame: up to 48 hours
measure: Effect of Food on AUC0-24h of HPG1860
timeFrame: 24 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Pharmaron CPC InC
state: Maryland
Study officials:
References: