A Phase 1 Study of TDM-105795 Topical Solution in Male Subjects With Androgenetic Alopecia (AGA)

Study Overview
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Brief Summary
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Multi-center, fixed volume, randomized, double-blind, vehicle-controlled, parallel group, dose escalation comparison study of TDM-105795 in male subjects, 18 to 55 years old, with Androgenetic Alopecia (AGA).

Detailed Description
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Protocol 239-11651-101 is a planned Phase 1 study entitled A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TDM-105795 Following a Fixed-Volume Topical Single Administration in Healthy Male Subjects with Androgenetic Alopecia. Eligible subjects will be assigned to a sequential treatment cohort and will receive either one of the TDM-105795 solutions or the Placebo. The assigned test article will be applied once onto the scalp in the hair loss area (e.g., top of head and temple areas). All subjects will be treated with 1 mL of test article with application to the scalp focusing on the regions that are bald and thinning.

Official Title
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A Randomized, Double-blind, Vehicle-controlled, Parallel Group, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single Dose TDM-105795 Topical Solution in Healthy Male Subjects With AGA

Conditions
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Alopecia, Androgenetic

Intervention / Treatment
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* Drug: TDM-105795
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To enter the study, a subject must meet the following criteria: Subject is male, 18-55 years old. Subject has provided written informed consent. Subject has a clinical diagnosis of moderate to severe AGA in temple and vertex region, IIIv to VI on the Modified Norwood-Hamilton Scale (i.e., IIIv, IV, V, and VI). Subject is willing and able to apply the test article(s) as directed, comply with study instructions, and commit to all follow-up visits for the duration of the study. Subject, in the investigator's opinion, is in good general health and free of any disease state or physical condition that might impair evaluation of AGA or exposes the subject to an unacceptable risk by study participation. Subject has normal renal, thyroid, and hepatic function as determined by the Visit 1/Screening laboratory results in the opinion of the investigator. Subject is a non-smoker, defined as not having smoked or used any form of tobacco or non-tobacco products containing nicotine in more than 6 months before Visit 2/Baseline. Subject has a body mass index (BMI) of 19 to 32 kg/m2 inclusive and body weight not less than 50 kg at Visit 1/Screening. Subject agrees to continue his other general hair care products and regimen for at least 2 weeks prior to Visit 2/Baseline, and through the entire study. Subjects who are sexually active with a female partner and are not surgically sterile (vasectomy performed at least 6 months prior to treatment) must agree to refrain from sperm donation for at least 1 week following initiation of study treatment and inform their female sexual partner to use a highly effective form of birth control as described in the informed consent form. For females, highly effective forms of birth control include 1) intrauterine device (IUD; copper or hormonal); 2) implantable hormonal contraception; 3) surgical sterilization (i.e., hysterectomy, tubal ligation, or bilateral oophorectomy) performed at least 6 months prior to the subject's study entry; 4) total abstinence; or 5) using one of each of the following a) hormonal contraceptives [other than IUD or implantable, e.g., oral, transdermal, injectable, or vaginal ring] and b) double barrier methods [i.e., male or female condom, diaphragm with spermicidal foam/gel/film/cream/vaginal suppository, cervical cap with spermicides, or contraceptive sponge]. Male subjects who become sexually active or begin to have relations with a female partner who is not sterile during the trial must have a female partner who agrees to use a highly effective form of birth control for the duration of the subject's participation in the trial. Female partner taking hormonal therapy must be on treatment prior to the subject's entry into the study, continued per label, and must not change their dosing regimen during the trial; highly effective birth control forms must be for (1) oral: at least 1 complete cycle (e.g., 4 to 8 weeks); (2) transdermal, injectable (e.g., Depo-Provera), implantable, vaginal ring (e.g., NuvaRing), IUD: at least 1 week; or (3) total abstinence: at least 1 complete cycle (e.g., 4 to 8 weeks) prior to initiation of test article. For males, adequate forms of contraception include condom and spermicide in combination with other forms of female contraception. Exclusion Criteria: A subject is ineligible to enter the study if he meets 1 or more of the following criteria: Subject has any dermatological disorders of the scalp on the regions that are bald and thinning with the possibility of interfering with the application of the test article or examination method, such as fungal or bacterial infections, seborrheic dermatitis, psoriasis, eczema, folliculitis, scars, or scalp atrophy. Subject has any skin pathology or condition (e.g., uncontrolled thyroid disease, certain genetic disorders that involve hair growth or patterns) that, in the investigator's opinion, could interfere with the evaluation of the test article or requires use of interfering topical, systemic, or surgical therapy. Subject has any visible inflammatory skin disease, injury, or condition of their scalp that could compromise subject safety and/or interfere with the evaluation of local or systemic assessments performed during the study. Subject has a history of scalp reduction or notable trauma with related scarring, hair transplants, and/or hair weaves. Subject has a known or suspected malignancy. Subject has a positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody. Subject has any condition, which, in the investigator's opinion, would make it unsafe for the subject to participate in this study, including clinically significant abnormal laboratory or 12-lead electrocardiogram (ECG) findings during the screening period or Visit 2/Baseline prior to dosing of the test article. Subject has a hospital admission or major surgery within 30 days prior to Visit 2/ Baseline or planned for during the study. Subject is currently enrolled in an investigational drug, biologic, or device study. Subject has used an investigational drug, investigational biologic, or investigational device treatment within 30 days or 5 half-lives, whichever is longer, prior to Visit 2/Baseline. Subject has a history of prescription drug abuse, or illicit drug use within 6 months prior to Visit 1/Screening. Subject has a history of alcohol abuse according to medical history within 6 months prior to Visit 1/Screening. Subject has a positive screen for alcohol or drugs of abuse at Visit 1/Screening or Visit 2/Baseline. Subject has a donation or blood collection of more than 1 unit (approximately 450 mL) of blood (or blood products) or acute loss of blood during the 90 days prior to Visit 2/Baseline. Subject has used prescription or over-the-counter (OTC) medications, or herbal (including St John's Wort, herbal teas, garlic extracts) supplements within 14 days prior to dosing at Visit 2/Baseline. (Note: Use of acetaminophen at < 3g/day is permitted until 24 hours prior to dosing at Visit 2/Baseline).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group, Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TDM-105795 Following a Fixed-Volume Topical Single Administration in Healthy Male Subjects with Androgenetic Alopecia
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SAD Cohorts 1 -3 TDM-105795 topical solution<br>Single dose administration of TDM-105795 Topical Solution, 0.0025% or 0.005% or 0.01% | Drug: TDM-105795<br>* TDM-105795 topical solution<br>|
| Placebo Comparator: Placebo for TDM-105795 topical solution<br>Single dose administration of Placebo forTDM-105795 Topical Solution | Drug: Placebo<br>* Placebo for TDM-105795 topical solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of any local and systemic AEs | Collection of adverse events | 8 days | 
| Number of subjects with presence (and severity) of local skin reactions (LSRs) | Collection of LSRs | 8 days | 
| Percent change from Baseline in vital signs | Collection of vital signs on day 1 and day 3 | 3 days | 
| Percent change from Baseline in safety labs | Collection of safety labs at day 2, 3, and 8 | 8 days | 
| Percent change from Baseline in overall interpretation of the ECG | Collection of ECGs at day 1, 3, and 8 | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of TDM-105795 | Plasma concentrations of TDM-105795 | 3 days |