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

This is a phase III, multi center, randomized, double blind, placebo and activecontrolled parallel group design clinical trial to evaluate the efficacy and safety oforal 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 otherclinically significant disease) and without any dermatological disorders (e.g., of thescalp in the target region at Visit 1/Screening with the possibility of interfering withthe application of the IPs or examination method).Patients must show and have a history of hair density reduction in the centroparietalarea 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 trialcenters across 4 countries (Germany, Spain, Italy, and Portugal) will enter the clinicaltrial.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 vehiclesolution (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 10tablets 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. Thepatients will be instructed how to apply the IPs. The first topical IP treatment will beperformed under supervision at the clinical trial center, and then treatments will beperformed 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 theevening/at night [preferably before going to bed to minimize anti hypertensive sideeffects]) and 2 ml assigned solution topically to the scalp BID (two topical applicationsof 1 ml each, to be performed at least 8 hours apart). Each patient will be requested torecord date and time of treatments in an electronic patient dosing diary (hereinaftercalled "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 forthe next 12 weeks.The clinical trial consists of a screening period (up to approximately 8 weeks, Week 8 toDay ‐2), a 6 month treatment period (Week 0 to 24), and a 4 week follow up period (Week25 to 28).It is planned to have five clinical trial center visits (Visit 1/Screening, Visit2/Baseline, Visit 4/Week 12, Visit 6/Week 24, and Visit 7/Week 28) and two safety phonecalls (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 andsafety will be evaluated and compared among the three treatment groups.The duration of clinical trial participation for each patient will be approximately up to36 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 trialrelated procedures (including washout). Once informed consent has been signed, thepatient 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 assessedby means of the TrichoLab Virtual Tattoo®technology which includes the taking of twomicrophotographs.If applicable, qualified patients can washout from prohibited medications or treatmentsprior to Visit 2/Baseline (after obtaining written informed consent). Patients mustreturn 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 Visit2/Baseline:Demographics, inclusions/exclusion criteria, relevant medical and relevant surgicalhistory of the past 5 years, and prior as well as concomitant medications and therapiesof the last 12 months will be reviewed. The patient's FAGA will be classified using theSinclair Scale. A brief physical examination, vital signs (blood pressure, pulse rate,body temperature), height and weight, safety laboratory tests (hematology, clinicalchemistry, and urinalysis), serum pregnancy test (only for women of childbearingpotential [WOCBP]), and 12 lead ECG will be performed. AEs will be recorded, asapplicable. Preliminary patient eligibility will be assessed, and, if applicable, thepatient will be scheduled for Visit 2/Baseline.During the clinical trial, safety will be assessed through physical examination, vitalsigns, weight, 12 lead ECG, and safety laboratory tests (hematology, clinical chemistry,and urinalysis) at each clinical trial center visit, except for safety laboratory whichwill not be performed at Visit 7/Week 28.Hypertrichosis evaluation will be performed at Visit 2/Baseline, Visit 4/Week 12, Visit6/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 timepoint the patient has signed the informed consent form (ICF) until the end of clinicaltrial.For all WOCBP, a urine pregnancy test will be performed at Visit 2/Baseline, Visit 4/Week12, and Visit 6/Week 24.During the clinical trial, efficacy will be determined based on quantitative hairmeasurements of Target Area non‐vellus Hair Counts (TAHC), Target Area non vellus HairWidth (TAHW), and Target Area non vellus Hair Density (TAHD) at each clinical trialcenter visit except for Visit 1/Screening and Visit 7/Week 28. TAHC, TAHW, and TAHD willbe determined by using TrichoLAB Hair‐to‐hair Matching® technology and digital imageanalysis.In addition, hair growth assessments will be performed by the investigator at Visit4/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 Visit2/Baseline. Furthermore, the patient's quality of life will be assessed by means of apatient self‐questionnaire (Women's Androgenetic Alopecia Quality of Life [WAA QoL] atVisit 2/Baseline Visit 4/Week 12 and Visit 6/Week 24.Statistical analyses will be conducted based on the available data, without usingtechniques for inputting missing values, but describing the number of missing values foreach analysis.All statistical tests will be performed at a significance level of α = 0.01, unlessspecifically stated otherwise.Prior to the database closure, a statistical analysis plan (SAP) will be approved inwhich the whole strategy of data analysis will be described in detail.