Study to Evaluate the Efficacy and Safety of P-3074 Topical Solution in the Treatment of Androgenetic Alopecia

Study Overview
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Brief Summary
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The purpose of this study is to confirm the clinical efficacy and the safety of P-3074 in participants with androgenetic alopecia.

Official Title
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A Multicentre, Randomized, Double-blind, Parallel-group, Controlled Study, to Assess the Efficacy and Safety of P-3074 Cutaneous Spray, Solution, in the Treatment of Male Pattern Baldness

Conditions
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Alopecia, Androgenetic

Intervention / Treatment
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* Drug: P-3074
* Drug: Finasteride
* Drug: P-3074 Vehicle
* Drug: Finasteride Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent before starting any study related procedures; Men 18 to 40 years of age; Men with mild to moderate vertex male pattern hair loss according to a modified Norwood/Hamilton classification scale (III vertex, IV or V); Participants willing to have a tattoo in the target area; Outpatients; Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; Ability to co-operate with the Investigator and to comply with the requirements of the entire study. Exclusion Criteria: Clinically relevant abnormal skin scalp findings which could interfere with the aim of the study; in particular, abrasion, actinic keratosis, inflammatory disorders or any other abnormality; Participants who had had hair transplant surgery or hair weaving; Clinically relevant abnormal laboratory values indicative of physical illness; Ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study; History of local infections of skin and subcutaneous tissues of the head in the 3-months period before the trial inclusion; Relevant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases, that may interfere with the aim of the study; Suspicion of malignancy, including prostate cancer; History of infertility or difficulty fathering children; Participants who wish to conceive children during the study or whose sexual partner(s) is pregnant; Participants with active seborrheic dermatitis; History of varicocele; Concurrent use of systemic corticosteroids, topical corticosteroids in the balding area studied, anabolic steroids, or over-the-counter hair restorers; Use of the following drugs with antiandrogenic properties within 6 months of study entry: flutamide, cyproterone acetate, estrogen, progesterone, cimetidine, spironolactone or ketoconazole; Participants who had been treated with any of the following drugs within the past year: minoxidil (topical or oral), zidovudine, cyclosporine, diazoxide, phenytoin, systemic interferon, psoralens, streptomycin, penicillamine, benoxaprofen, tamoxifen, phenothiazines or cytotoxic agents; Use of finasteride or dutasteride within previous 12 months; Light or laser treatment of scalp within previous 3 months; Participation in the evaluation of any drug for 3 months before this study, calculated from the first day of the month following the last visit of the previous study; History of drug, alcohol [>2 drinks/day defined according to USDA Dietary Guidelines 2010], caffeine (>5 cups coffee/tea/day) or tobacco abuse (10 cigarettes/day).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: P-3074 + Finasteride Placebo<br>Participants received topical application of P-3074 contained finasteride 0.25% in morning onto dry scalp only (up to 4 puffs) and followed by placebo of finasteride 1 milligram (mg) tablet orally once daily for 24 weeks. | Drug: P-3074<br> <br> * Other names: finasteride topical solution;Drug: Finasteride Placebo<br> <br> * Other names: Placebo of Finasteride;|
| Placebo Comparator: P-3074 Vehicle + Finasteride Placebo<br>Participants received topical application of P-3074 vehicle in morning onto dry scalp only (up to 4 puffs) and followed by placebo of finasteride 1 mg tablet orally once daily for 24 weeks. | Drug: P-3074 Vehicle<br> <br> * Other names: Vehicle of P-3074;Drug: Finasteride Placebo<br> <br> * Other names: Placebo of Finasteride;|
| Active Comparator: Oral Finasteride + P-3074 Vehicle<br>Participants received finasteride 1 mg tablet orally once daily followed by topical application of P-3074 vehicle in morning onto dry scalp only (up to 4 puffs) for the 24 weeks. | Drug: Finasteride<br> <br> * Other names: Propecia;Drug: P-3074 Vehicle<br> <br> * Other names: Vehicle of P-3074;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Hair Growth Assessed by Target Area Hair Count (TAHC) in the Vertex at Week 24 | The change from baseline in the TAHC within a 1 cm^2 (square centimeter) of baldness area at Week 24, were assessed by macro photographic techniques analysis. The Investigator selected a target area in the anterior leading edge of the vertex thinning area. A small dot tattoo was placed in the center of the circle of the clipped hairs. Using the tattoo as a reference point, the circular area was photographed and a 1 cm^2 circular area within the target area was analysed. Change is the adjusted mean of Week 24 minus baseline.The analysis uses a covariance pattern model adjusted for treatment group, center, visit and treatment-by-visit interaction as fixed effects and baseline hair count as a covariate with an unstructured covariance structure. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Hair Growth Assessed by TAHC in the Vertex at Week 12 | The change from baseline in the TAHC within a 1 cm^2 of baldness area at Week 12, were assessed by macro photographic techniques analysis. The Investigator selected a target area in the anterior leading edge of the vertex thinning area. A small dot tattoo was placed in the center of the circle of the clipped hairs. Using the tattoo as a reference point, the circular area was photographed and a 1 cm^2 circular area within the target area was analysed. Change is the adjusted mean of Week 24 minus baseline.The analysis uses a covariance pattern model adjusted for treatment group, center, visit and treatment-by-visit interaction as fixed effects and baseline hair count as a covariate with an unstructured covariance structure. | Baseline and Week 12 | 
| Adjusted Mean Change From Baseline in Target Area Hair Width (TAHW) in the Vertex at Weeks 12 and 24 | The change from baseline in the TAHW within a 1 cm^2 of baldness area at Weeks 12 and 24, were assessed by macro photographic techniques analysis. The Investigator selected a target area in the anterior leading edge of the vertex thinning area. A small dot tattoo was placed in the center of the circle of the clipped hairs. Using the tattoo as a reference point, the circular area was photographed and a 1 cm^2 circular area within the target area was analysed. Change is the adjusted mean of Weeks 12 and 24 minus baseline, respectively.The analysis uses a covariance pattern model adjusted for treatment group, center, visit and treatment-by-visit interaction as fixed effects and baseline hair count as a covariate with an unstructured covariance structure. | Baseline, Week 12 and Week 24 | 
| Adjusted Mean Overall Male Hair Growth Questionnaire (MHGQ) Score as Assessed by the Participant at Weeks 12 and 24 | Participants assessed their scalp hair using a validated, self-administered MHGQ, which was given in their language. The self-administered MHGQ overall score assessed using the following 5-point scale: 1 = very satisfied, 2 = satisfied, 3 = neutral (neither satisfied nor dissatisfied), 4 = dissatisfied, 5 = very dissatisfied. A higher score indicated a worse outcome. The questionnaire was administered to eligible participants to subjectively measure their perception of hair growth. A higher score indicated a worse outcome. | Week 12 and Week 24 | 
| Adjusted Mean Change From Baseline in Participants Hair Growth/Loss Assessed for the Vertex by Investigator at Weeks 12 and 24 | The local Investigator assessed change in hair growth from Baseline to Week 12 and from Baseline to Week 24, using a 7-point scale. The evaluation was done by the Investigator or designee, by comparing the global vertex view photograph obtained at baseline visit with the participants actual scalp at 12 and 24 weeks. For the purpose of assessment of changes in hair growth by Investigators screening visits (where global photos were taken) were used as Baseline. The change from Baseline in hair growth was assessed using the following 7-point scale: -3 = greatly decreased, -2 = moderately decreased, -1 = slightly decreased, 0 = no change, +1 = slightly increased, +2 = moderately increased, +3 = greatly increased. The analysis uses a covariance pattern model adjusted for treatment group, center, visit and treatment-by-visit interaction as fixed effects with an unstructured covariance structure. | Baseline, Week 12 and Week 24 | 
| Adjusted Mean Change From Baseline in Participants Hair Growth/Loss at Weeks 12 and 24, Assessed for the Vertex by Blind Assessor | An independent blinded assessor was responsible for evaluating, under blinded conditions, the screening global photographs of the target area for all participants. They evaluated the eligibility of each participants according to the clinical inclusion criteria. The independent blinded assessor assessed the change of the hair growth from Baseline to Week 12 and from Baseline to Week 24, using a 7-point scale: -3 = greatly decreased, -2 = moderately decreased, -1 = slightly decreased, 0 = no change, +1 = slightly increased, +2 = moderately increased, +3 = greatly increased. This assessment was performed by comparing the global photographs obtained at screening visit with those subsequently obtained at Weeks 12 and 24. The analysis uses a covariance pattern model adjusted for treatment group, center, visit and treatment-by-visit interaction as fixed effects with an unstructured covariance structure. | Baseline, Week 12 and Week 24 | 
| Adjusted Mean International Index of Erectile Function (IIEF-2) Scores at Weeks 4, 8, 12 and 24 | The 15-question IIEF-2 Questionnaire (Sexual Function Questionnaire) was used to evaluate any changes in sexual function and activity, at Weeks 4, 8, 12 and 24. A score of 0-5 is awarded to each of the 15 questions that examine the 4 main domains of male sexual function: erectile function, orgasmic function, sexual desire and intercourse satisfaction. Erectile function domain has 6 questions with the score for domain range from 0-30. Orgasmic function domain has 2 questions with the score for domain range from 0-10. , Sexual desire function domain has 2 questions with the score for domain range from 0-10. Intercourse satisfaction function domain has 3 questions with the score for domain range from 0-15. Overall Satisfaction domain has 2 questions with the score for domain range from 0-10. A higher score indicated a worse outcome in that domain. | Weeks 4, 8, 12 and 24 | 
| Local Tolerability as Assessed by Incidence Rate of Skin Irritation Event Via Severity Score for Skin Irritation Scale | Local tolerability at the application site was assessed to rate the severity of any skin irritation. The Investigator used the Severity score for skin Irritation scale to assess local tolerability. The dermal response and other effects indicative irritation responses were recorded at time of examination. Anything other than No evidence of irritation under Dermal Response was considered as a Dermal Response Skin Irritation event. Anything other than No other effects under Other Effects was considered as an Other Effects of Skin Irritation event. The event incidence rate is calculated as the number of events interest divided by total personal time in years. | Baseline to Week 24 | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | An Adverse event is defined as any untoward medical occurrence in a participants or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with treatment. A serious AE was an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect and medically significant event. The Treatment Emergent Adverse Events (TEAEs) is defined as all AEs occurring on or after the first dose of the IMP. | From the start of IMP up to 28 weeks |