Evaluation of Efficacy and Safety of Oral Minoxidil 1 mg in Female Androgenetic Alopecia

Overview

The goal of this clinical trial is to learn about oral minoxidil 1mg in the treatment of women with androgenetic alopecia, a type of hormone-imbalanced hair loss. The main questions to answer are to know about that minoxidil 1mg is as effective as minoxidil 2% topical solution (comparator product) and is more effective than placebo; and to ensure treatment with oral minoxidil is safe. Participants will be assigned randomly to receive one of the following treatment combinations: * the test product (oral minoxidil 1 mg, once/day) and the vehicle solution (vehicle means it looks like the comparator product, but it does not contain an active ingredient, 2 times/day), or * the placebo tablet (placebo means it looks like the test product, but it does not contain an active ingredient, once/day) and the comparator product (2% minoxidil solution, 2 times/day), or * the placebo tablet (once/day) and the vehicle solution (2 times/day). The clinical trial will take up to 36 weeks. During this time, patients will come to the clinical trial centre for 5 times for examinations and will be called by phone twice. At the visits, the following examinations will be performed: photos of the hair will be taken to determine hair density, assessment of changes in scalp hair growth, measurement of blood pressure, pulse, and body temperature, a physical examination, blood withdrawal to determine any abnormalities in the blood, urine sampling and analysis, performance of ECG, and evaluation of hypertrichosis (i.e., excessive hair growth over the body). Furthermore, patients will be asked daily whether they had experienced any side effects or took any new medications (or changed the dose of a known medication) or underwent any medical procedure. Also, women of childbearing potential must undergo pregnancy tests in blood and urine.

This is a phase III, multi center, randomized, double blind, placebo and active controlled parallel group design clinical trial to evaluate the efficacy and safety of oral minoxidil 1 mg for the treatment of AGA in female\* patients aged 18 years or older, with general good health (i.e., with no history of cardiovascular disorders, or any other clinically significant disease) and without any dermatological disorders (e.g., of the scalp in the target region at Visit 1/Screening with the possibility of interfering with the application of the IPs or examination method). Patients must show and have a history of hair density reduction in the centroparietal area of the scalp, as classified by the Sinclair Scale (Sinclair Scale 2-4). It is planned that approximately 520 adult female patients with FAGA from 20 trial centers across 4 countries (Germany, Spain, Italy, and Portugal) will enter the clinical trial. Eligible patients will be randomly assigned in a ratio 2:2:1 (active: control: placebo) to one of the following 3 treatment groups: 1. Active group: oral minoxidil 1 mg (1 tablet, once daily \[OD\]) + topical vehicle solution (1 ml, twice daily \[BID\]) 2. Control group: oral placebo (1 tablet, OD) + topical 2% minoxidil solution (1 ml, BID) 3. Placebo group: oral placebo (1 tablet, OD) + topical vehicle solution (1 ml, BID) At Visit 2/Baseline, patients will receive three boxes containing 5 blister packs of 10 tablets each (a total of 50 tablets) and 4 bottles of IP solution containing 60 ml of 2% minoxidil solution each to cover 12 weeks (±7 days) of clinical trial treatment. The patients will be instructed how to apply the IPs. The first topical IP treatment will be performed under supervision at the clinical trial center, and then treatments will be performed by the patients at home (also the intake of the first tablet), as follows: Patients will administer the assigned IPs daily for 6 months-one tablet orally OD (in the evening/at night \[preferably before going to bed to minimize anti hypertensive side effects\]) and 2 ml assigned solution topically to the scalp BID (two topical applications of 1 ml each, to be performed at least 8 hours apart). Each patient will be requested to record date and time of treatments in an electronic patient dosing diary (hereinafter called "electronic diary \[e-diary\]"). At the next planned clinical trial center visit (Visit 4/Week 12), the patients will receive a new batch of clinical trial treatment for the next 12 weeks. The clinical trial consists of a screening period (up to approximately 8 weeks, Week 8 to Day -2), a 6 month treatment period (Week 0 to 24), and a 4 week follow up period (Week 25 to 28). It is planned to have five clinical trial center visits (Visit 1/Screening, Visit 2/Baseline, Visit 4/Week 12, Visit 6/Week 24, and Visit 7/Week 28) and two safety phone calls (Visit 3/Week 4 and Visit 5/Week 18) during the course of the clinical trial; unscheduled visits may be needed per the discretion of the investigator. Efficacy and safety will be evaluated and compared among the three treatment groups. The duration of clinical trial participation for each patient will be approximately up to 36 weeks. At the screening visit, the clinical trial requirements and procedures will be reviewed. Written informed consent will be obtained prior to the initiation of any clinical trial related procedures (including washout). Once informed consent has been signed, the patient will be assigned a patient number. The suitability of the patient hair color (sufficient contrast with the scalp) for re-detection of the target area will be assessed by means of the TrichoLab Virtual Tattoo®technology which includes the taking of two microphotographs. If applicable, qualified patients can washout from prohibited medications or treatments prior to Visit 2/Baseline (after obtaining written informed consent). Patients must return to the clinical trial center after washout for completion of screening procedures. The following screening procedures must take place up to within 8 weeks of Visit 2/Baseline: Demographics, inclusions/exclusion criteria, relevant medical and relevant surgical history of the past 5 years, and prior as well as concomitant medications and therapies of the last 12 months will be reviewed. The patient's FAGA will be classified using the Sinclair Scale. A brief physical examination, vital signs (blood pressure, pulse rate, body temperature), height and weight, safety laboratory tests (hematology, clinical chemistry, and urinalysis), serum pregnancy test (only for women of childbearing potential \[WOCBP\]), and 12 lead ECG will be performed. AEs will be recorded, as applicable. Preliminary patient eligibility will be assessed, and, if applicable, the patient will be scheduled for Visit 2/Baseline. During the clinical trial, safety will be assessed through physical examination, vital signs, weight, 12 lead ECG, and safety laboratory tests (hematology, clinical chemistry, and urinalysis) at each clinical trial center visit, except for safety laboratory which will not be performed at Visit 7/Week 28. Hypertrichosis evaluation will be performed at Visit 2/Baseline, Visit 4/Week 12, Visit 6/Week 24 (end of treatment \[EoT)/early termination visit \[ETV\]), and Visit 7/Week 28. AEs, as well as concomitant medication, and procedures will be documented from the time point the patient has signed the informed consent form (ICF) until the end of clinical trial. For all WOCBP, a urine pregnancy test will be performed at Visit 2/Baseline, Visit 4/Week 12, and Visit 6/Week 24. During the clinical trial, efficacy will be determined based on quantitative hair measurements of Target Area non-vellus Hair Counts (TAHC), Target Area non vellus Hair Width (TAHW), and Target Area non vellus Hair Density (TAHD) at each clinical trial center visit except for Visit 1/Screening and Visit 7/Week 28. TAHC, TAHW, and TAHD will be determined by using TrichoLAB Hair-to-hair Matching® technology and digital image analysis. In addition, hair growth assessments will be performed by the investigator at Visit 4/Week 12 and Visit 6/Week 24 (Investigator's Global Assessment \[IGA, 7 point scale\]), using the standardized approved global photo of the patient's scalp taken at Visit 2/Baseline. Furthermore, the patient's quality of life will be assessed by means of a patient self-questionnaire (Women's Androgenetic Alopecia Quality of Life \[WAA QoL\] at Visit 2/Baseline Visit 4/Week 12 and Visit 6/Week 24. Statistical analyses will be conducted based on the available data, without using techniques for inputting missing values, but describing the number of missing values for each analysis. All statistical tests will be performed at a significance level of α = 0.01, unless specifically stated otherwise. Prior to the database closure, a statistical analysis plan (SAP) will be approved in which the whole strategy of data analysis will be described in detail.