To Evaluate the Safety, Tolerability and PK of GT20029 Gel and Solution in Healthy Subjects

Phase 1

Completed

• Conditions: Acne; Alopecia
• Interventions: Drug: GT20029 matching placebo; Drug: GT20029

• Registration Number: NCT06468579
• Lead Sponsor: Suzhou Kintor Pharmaceutical Inc,

Brief Summary

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

Detailed Description

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 Timeline

• Study Start: 2021-07-25
• Primary Completion: 2022-08-15
• Study Completion: 2023-04-26
• Status Verified: 2024-05
• Study First Submitted: 2024-05-27
• Study First Submitted QC: 2024-06-16
• Study First Posted: 2024-06-21
• Last Update Submitted: 2024-10-20
• Last Update Posted: 2024-10-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

Patients who meet all of the following criteria may be included in this study:

1. Subjects aged 18 to 60 years (including the boundary value), male or female;
2. Male weight ≥ 50 kg, female weight ≥ 45 kg, body mass index (BMI) between 19 and 26 kg/m2 inclusive;
3. The subject voluntarily participates in the clinical trial and signs the informed consent form, is able to communicate well with the investigator, and understands and complies with the requirements of this study;
4. From signing the informed consent form to 3 months after the last dose, fertile female subjects or partners of fertile male subjects agree to and can take effective contraceptive measures, such as avoiding sex or using condoms, intrauterine device and other reliable contraceptive measures;
5. Willing to use the investigational drug as required during the trial and refrain from using any other medication while receiving the investigational drug.

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from the study:

1. Previous allergy to the investigational drug and/or any excipients, or allergic constitution (such as two or more drugs, food or pollen allergy);
2. Currently suffering from skin diseases requiring treatment and researchers believe that it is not suitable for enrollment, such as solar dermatitis, psoriasis, seborrheic dermatitis, rosacea, folliculitis, eczema and very severe acne;
3. Previous or current suffering from the following diseases and researchers believe that cannot be enrolled, including but not limited to nervous system, cardiovascular system, blood and lymphatic system, immune system, kidney, liver, gastrointestinal tract, respiratory system, metabolism and bone and other system diseases and malignant tumors;
4. Screening physical examination, vital signs, laboratory tests (blood routine, urine routine, blood biochemistry, coagulation function, etc.), 12-lead ECG results are abnormal and clinically significant, and have an impact on the evaluation of this trial;
5. Subjects who plan to use various skin care products simultaneously on the back skin during the trial;
6. Blood collection difficulties or cannot tolerate venipuncture, have a history of fainting needle halo blood;
7. Blood donation or blood loss ≥ 200 mL within 3 months before screening, or plan to donate blood or blood components during the study or within 3 months after the end of the study;
8. Smoking more than 5 cigarettes per day within 3 months before screening and those who cannot abstain from smoking throughout the trial;
9. Drink more than 14 units of alcohol per week (1 unit of alcohol ≈ 360 mL beer or 45 mL of spirits with 40% alcohol content or 150 mL wine) within 3 months before signing the informed consent form, or have a positive breath alcohol test on the day before administration (breath alcohol content > 0.0 mg/100 mL), or cannot abstain from alcohol during the trial;
10. Patients who have been drinking excessive tea, coffee or caffeine-containing beverages for a long time (more than 8 cups a day, 1 cup = 200 mL);
11. Consumption of any food or beverage containing caffeine, alcohol, xanthine or grapefruit ingredients (such as coffee, strong tea, chocolate, etc.) within 48 hours before the first dose;
12. Use of any drugs (including prescription drugs, over-the-counter drugs, Chinese herbal medicines, etc.) or health products within 14 days or 7 half-lives (whichever is the longest) before the first dose;
13. Use of any known liver enzyme inducer or liver enzyme inhibitor within 30 days before the first dose ;
14. Use of drugs with the same target and mechanism (androgen receptor degraders) within 1 month before screening;
15. Drug addiction and drug abuse test one or more positive, 1 year before the test drug abuse/dependence history or drug history;
16. Human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C virus antibody, treponema pallidum antibody test positive;
17. Pregnant or lactating women or female subjects with positive blood pregnancy during screening period;
18. Subjects with back application site skin damage or wounds, tattoos or scars;
19. Planned to participate in strenuous exercise during the trial, including body contact exercise or collision exercise;
20. Major surgery within 3 months before screening, or plan to undergo major surgery during the trial;
21. Participating or participating in any drug or medical device clinical trial within 3 months before screening;
22. Unable to communicate or cooperate with medical staff due to neurological, psychiatric or language disorders;
23. Other conditions that the investigator considers unsuitable for participating in the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Comparator: GT20029 Placebo	GT20029 matching placebo	-
Experimental: GT20029	GT20029	-

Primary Outcome Measures

Name	Time	Method
Evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of GT20029 for single dose and multi dose topical administration in healthy subjects.	14 days	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

Secondary Outcome Measures

Name	Time	Method
To characterize the area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) of GT20029	14 days	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
To characterize the area under the apparent volume of distribution (Vd/F) of GT20029	14 days	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
To characterize the area under the apparent clearance (CL/F) of GT20029	14 days	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
To characterize the time to peak concentration (Tmax) of GT20029	14 days	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
To characterize the area under the concentration-time curve from time zero to infinity (AUC0-∞) of GT20029	14 days	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-∞
Evaluate the ratio of systemic exposure between the gel and solution formulation.	14 days	Evaluate the ratio of systemic exposure between the gel and solution formulation by using GT20029 gel as a reference.
To characterize the area under the terminal elimination rate constant (λz) of GT20029	14 days	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
To characterize the peak concentration at steady state (Cmax,ss) of GT20029	14 days	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
To characterize the peak concentration (Cmax) of GT20029	14 days	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
To characterize the elimination half-life (t1/2) of GT20029	14 days	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
To characterize the area under the concentration-time curve at steady state (AUCss) of GT20029	14 days	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
To characterize the trough concentration at steady state (Cmin,ss) of GT20029	14 days	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
To characterize the time to peak concentration at steady state (Tmax,ss) of GT20029	14 days	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

Trial Locations

Locations (1)

Clinical Pharmacology Research Center, Huashan Hospital, Fudan University; 🇨🇳 Shanghai, Shanghai, China