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A Phase I Study of GFH312 in Healthy Chinese Subjects

Phase 1
Completed
Conditions
Healthy Volunteer
Interventions
Drug: GFH312 200 mg
Drug: GFH312 120mg
Other: Placebo
Drug: GFH312 100 mg
Registration Number
NCT05991362
Lead Sponsor
Zhejiang Genfleet Therapeutics Co., Ltd.
Brief Summary

The aim of this study was to evaluate the pharmacokinetic profile and observe the safety of GFH312 after single and multiple administrations in healthy Chinese subjects.

Detailed Description

This study was planned to enroll about 26 healthy subjects, subjects were planned to receive single administration of 100 mg GFH312, single administration of 200 mg GFH312, or multiple administrations of 120 mg GFH312, as well as their matching placebo. Subjects were randomized in 3:1 ratio in the single dose cohorts and in 4:1 ratio in the multiple dose cohort.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
26
Inclusion Criteria
  • Voluntarily participate in the study and sign the informed consent;
  • Male or female healthy subjects aged 18-55 years (inclusive) (single sex ratio not less than 25% of the sample size of each cohort);
  • Body mass index (BMI) between 18-28 kg/m2 (inclusive), and weight ≥ 50kg; BMI = Weight (kg) /[Height (m)]2.
  • During the screening period and day 1, patients with normal or abnormal results but no clinical significance based on detailed medical history, comprehensive physical examination, laboratory examination (blood routine, blood biochemistry, urine routine, coagulation function), 12-lead electrocardiogram and vital signs.
  • Able to communicate well with researchers, understand and comply with research requirements.
Exclusion Criteria
  • Any procedure or disease that may significantly alter drug absorption, distribution, metabolism, or excretion, or participation in this study may compromise the safety of the subject.
  • Tuberculin test positive
  • Abnormal electrocardiogram with clinical significance
  • Use any prescription drugs, Chinese herbs and/or OTC or health products within 2 weeks before starting the administration.
  • Women who are pregnant or breastfeeding, or subjects with positive pregnancy test results at the time of screening or at baseline, or who plan to become pregnant during the study period or within 30 days after the end of the study.
  • Subjects who have any factors deemed unsuitable for participation in this study by the investigator.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SAD:200mgGFH312 200 mgParticipants received single PO dose of GFH312 200 mg.
MAD:120mgGFH312 120mgParticipants received multiple PO doses of GFH312 120 mg for 14 days.
PlaceboPlaceboParticipants receiving placebo matching with the GFH312 dose groups
SAD:100mgGFH312 100 mgParticipants received single PO dose of GFH312 100 mg.
Primary Outcome Measures
NameTimeMethod
The apparent volume of distribution during the terminal elimination phase (Vd/F) following extravascular administration of GFH312For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4; for multiple doses groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 8, 12 hours on day 1; day2, day7, day 13, day14, day15.

The volume of distribution was estimated based on the plasma concentrations of GFH312

The lowest plasma (or serum or blood) concentration observed during a dosing interval at steady state (Cmin,ss)For multiple doses groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 8, 12 hours on day 1; day2, day7, day 13, day14, day15.

Observed minimum concentration in the dosing interval at steady state.

Time to reach maximum concentration in the dosing interval at steady state (Tmax,ss)For multiple doses groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 8, 12 hours on day 1; day2, day7, day 13, day14, day15.

If the same Cmax concentration occurs at different time points, Tmax is assigned to the first occurrence of Cmax.

The area under the plasma (or serum or blood) concentration-time curve from time zero to the end of the dosing interval tau (AUCtau,ss)For multiple doses groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 8, 12 hours on day 1; day2, day7, day 13, day14, day15.

Dose-normalized AUC0- τ, calculated as AUC0-τ divided by actual dose administered.

Maximum Observed Plasma Concentration (Cmax) of GFH312For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4.

The maximum observed plasma concentration (Cmax) was estimated based on the plasma concentrations of GFH312.

Time to peak drug concentration (Tmax) of GFH312For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4.

The time it takes for a drug to reach the maximum concentration (Cmax) after administration of GFH312

Terminal Elimination Half Life (t1/2) of GFH312For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4; for multiple doses groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 8, 12 hours on day 1; day2, day7, day 13, day14, day15.

The terminal elimination half-life (t1/2) was estimated based on the plasma concentrations of GFH312

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of GFH312For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4.

The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last) was estimated based on the plasma concentrations of GFH312

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of GFH312For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4.

The area under the plasma concentration-time curve from time zero to infinity (AUC 0-inf) was estimated based on the plasma concentrations of GFH312

The apparent systemic (or total body) clearance from plasma (or serum or blood (CL/F) following extravascular administration of GFH312For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4; for multiple doses groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 8, 12 hours on day 1; day2, day7, day 13, day14, day15.

The systemic clearance (CL) was estimated based on the plasma concentrations of GFH312

The observed maximum plasma (or serum or blood) concentration following drug administration at steady state (Cmax,ss)For multiple doses groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 8, 12 hours on day 1; day2, day7, day 13, day14, day15.

Observed maximum concentration in the dosing interval at steady state

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)up to 30 days after the last study drug administration

An adverse event (AE) is any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability or incapacity; congenital anomaly or birth defect in the offspring of a participant who received the study drug.

Trial Locations

Locations (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

🇨🇳

Wuhan, Hubei, China

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