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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: HPG1860

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 Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pharmaron CPC InC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hepagene (Shanghai) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2019
• Primary Completion (Actual): November 25, 2020
• Study Completion (Actual): August 7, 2021

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 22, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: HPG1860-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No