The study is a randomized, double-blind, vehicle-controlled, parallel group, phase 1 study to evaluate the Safety, Tolerability and PK of GT20029 in healthy subjects
GT20029 is a new investigational androgen receptor (AR) degrader for the treatment of acne and androgenetic alopecia. A total of 92 healthy subjects planned to be enrolled. It is divided into a single dose dosage stage and a multi dose dosage stage. This study comprised two stages. Stage 1 included single ascending dose (SAD) and multiple ascending dose (MAD) parts. In the SAD part, 28 subjects were first enrolled to evaluate GT20029 gel or the corresponding vehicle (placebo) at four dosing levels: 1 mg, 2 mg, 5 mg, and 10 mg. In the MAD part, 40 subjects were enrolled with five dosing levels: 2 mg QD, 2 mg Q12h, 5 mg QD, 5 mg Q12h, and 10 mg QD for 14 consecutive days. SAD subjects could transfer to the MAD QD dosing cohort at the same dosing level after a 14-day wash-out period if safety was confirmed by the investigator. In Stage 2, 24 subjects were enrolled to evaluate GT20029 solution or the corresponding vehicle (placebo) in the MAD part for 14 days with three dosing levels: 5 mg QD, 10 mg QD, and 20 mg QD. The administration site was an 8 cm by 8 cm area selected on the subjects' backs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
92
Stage 1: GT20029 gel single ascending dose (1mg, 2mg, 5mg, 10mg) with 14 days washout window; Multi ascending dose (2mg QD, 2mg Q12h, 5mg QD, 5mg Q12h,10mg QD) for 14 consecutive days; Stage 2: GT20029 solution multi ascending dose (5mg QD, 10mg QD, 20mg QD) for 14 consecutive days;
Stage 1: GT20029 gel matching placebo single ascending dose (1mg, 2mg, 5mg, 10mg) with 14 days washout window; Multi ascending dose (2mg QD, 2mg Q12h, 5mg QD, 5mg Q12h,10mg QD) for 14 consecutive days; Stage 2: GT20029 solution matching placebo multi ascending dose (5mg QD, 10mg QD, 20mg QD) for 14 consecutive days;
Clinical Pharmacology Research Center, Huashan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
Evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of GT20029 for single dose and multi dose topical administration in healthy subjects.
Incidence of Treatment Emergent Adverse Events, as assessed by Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, V2.1
Time frame: 14 days
To characterize the peak concentration (Cmax) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration is: Stage 1, single-dose administration, Cmax
Time frame: 14 days
To characterize the time to peak concentration (Tmax) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration is: Stage 1, single-dose administration, Tmax
Time frame: 14 days
To characterize the elimination half-life (t1/2) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration is: Stage 1, single-dose administration, t1/2
Time frame: 14 days
To characterize the area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration is: Stage 1, single-dose administration, AUC0-t
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Time frame: 14 days
To characterize the area under the concentration-time curve from time zero to infinity (AUC0-∞) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration is: Stage 1, single-dose administration, AUC0-∞
Time frame: 14 days
To characterize the area under the terminal elimination rate constant (λz) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration is: Stage 1, single-dose administration, λz
Time frame: 14 days
To characterize the area under the apparent volume of distribution (Vd/F) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration is: Stage 1, single-dose administration, Vd/F
Time frame: 14 days
To characterize the area under the apparent clearance (CL/F) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration is: Stage 1, single-dose administration, CL/F
Time frame: 14 days
To characterize the area under the concentration-time curve at steady state (AUCss) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration are: Stage 1, multi-ascending dose and Stage 2, AUCss
Time frame: 14 days
To characterize the peak concentration at steady state (Cmax,ss) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration are: Stage 1, multi-ascending dose and Stage 2, Cmax,ss
Time frame: 14 days
To characterize the trough concentration at steady state (Cmin,ss) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration are: Stage 1, multi-ascending dose and Stage 2, Cmin,ss
Time frame: 14 days
To characterize the time to peak concentration at steady state (Tmax,ss) of GT20029
The plasma concentration time data for GT20029 and its metabolite will be analyzed using noncompartmental methods. Actual dosing and sampling times will be used for analyses. The primary PK parameters of interest following dose administration are: Stage 1, multi-ascending dose and Stage 2, Tmax,ss
Time frame: 14 days
Evaluate the ratio of systemic exposure between the gel and solution formulation.
Evaluate the ratio of systemic exposure between the gel and solution formulation by using GT20029 gel as a reference.
Time frame: 14 days