A Phase I Study of GFH312 in Healthy Chinese Subjects

NCT05991362 | Completed Phase 1

• 1 other identifier: GFH312X1102
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (11)

• Maximum Observed Plasma Concentration (Cmax) of GFH312

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

  For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4.

• Time to peak drug concentration (Tmax) of GFH312

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

  For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4.

• Terminal Elimination Half Life (t1/2) of GFH312

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

  For 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.

• Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of GFH312

  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

  For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4.

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of GFH312

  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

  For single dose groups 30 minutes pre-dose, and at 0.5, 1, 2, 4, 6, 8, 12 hours on day1; day2, day3, day4.

• The apparent systemic (or total body) clearance from plasma (or serum or blood (CL/F) following extravascular administration of GFH312

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

  For 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 apparent volume of distribution during the terminal elimination phase (Vd/F) following extravascular administration of GFH312

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

  For 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 observed maximum plasma (or serum or blood) concentration following drug administration at steady state (Cmax,ss)

  Observed maximum concentration in the dosing interval at steady state

  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 lowest plasma (or serum or blood) concentration observed during a dosing interval at steady state (Cmin,ss)

  Observed minimum concentration in the dosing interval at steady state.

  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.

• Time to reach maximum concentration in the dosing interval at steady state (Tmax,ss)

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

  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 area under the plasma (or serum or blood) concentration-time curve from time zero to the end of the dosing interval tau (AUCtau,ss)

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

  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.

Secondary Outcomes (1)

• 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

Study Arms (4)

SAD:100mg

EXPERIMENTAL

Participants received single PO dose of GFH312 100 mg.

Drug: GFH312 100 mg

SAD:200mg

EXPERIMENTAL

Participants received single PO dose of GFH312 200 mg.

Drug: GFH312 200 mg

MAD:120mg

EXPERIMENTAL

Participants received multiple PO doses of GFH312 120 mg for 14 days.

Drug: GFH312 120mg

Placebo

PLACEBO COMPARATOR

Participants receiving placebo matching with the GFH312 dose groups

Other: Placebo

Interventions

GFH312 100 mg DRUG

Participants receive single dose of GFH312 100 mg orally

Also known as: GFH312

SAD:100mg

GFH312 200 mg DRUG

Participants receive single dose of GFH312 200 mg orally

Also known as: GFH312

SAD:200mg

GFH312 120mg DRUG

Participants receive daily dose of GFH312 120mg orally for fourteen consecutive days

Also known as: GFH312

MAD:120mg

Placebo OTHER

Participants receive placebo matching with GFH312

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang Genfleet Therapeutics Co., Ltd.: lead

Study Sites (1)

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

Wuhan, Hubei, China

Location

Study Officials

• LU Yongning, PHD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2023
• First Posted: August 14, 2023
• Study Start: November 29, 2022
• Primary Completion: February 13, 2023
• Study Completion: May 30, 2023
• Last Updated: August 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)