A Study To Assess The Efficacy And Safety Of Dutasteride 0.5mg Once Daily For 6 Months In The Treatment Of Male Subjects With Androgenetic Alopecia

Study Overview
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Brief Summary
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The aim of this Phase III study is to compare the efficacy, safety and tolerability of dutasteride (0.5mg) with placebo for 6 months, in Korean male subjects with androgenetic alopecia in the vertex region, types IIIv, IV and V according to the modified Norwood-Hamilton Classification.

Official Title
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An Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of Dutasteride 0.5mg Once Daily for 6 Months in the Treatment of Male Subjects With Androgenetic Alopecia (Norwood-Hamilton Classification Type IIIv, IV and V)

Conditions
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Alopecia

Intervention / Treatment
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* Drug: Dutasteride 0.5mg oral tablets


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Rationale - The vertex area of the scalp will be evaluated during this study, therefore the inclusion criterion of Norwood Hamilton areas IIIv, IV or V ensures that subjects with vertex hair loss will be recruited in line with the primary efficacy endpoint of change in hair growth in the vertex. A subject will be eligible for inclusion in this study only if all of the following criteria apply: Male out-patients aged 18-49 years, inclusive Diagnosis of Male Pattern Hair Loss classified as type IIIv, IV, or V utilising the modified Norwood-Hamilton classification (Figure 1) (N.B. types IVa and Va are excluded) Able to comprehend instructions and record required information Will provide signed and dated written informed consent to participate in this investigation Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: Evidence of hypogonadism defined as serum testosterone < 250ng/dl and/or LH >20mIU/ml Note: If the initial serum testosterone result is < 250ng/dl and the LH value is normal, the test may be repeated once. Attempts should be made, where possible, to collect all samples in the morning hours. If the repeat testosterone result is < 250ng/dl, the subject is not eligible for participation. Greater than two times the upper limit of normal for ALT or AST, or a bilirubin greater than 2.0mg/dl (exception - subjects diagnosed with Gilbert's syndrome will be eligible to participate in the study) Serum creatinine >1.8mg/dl Global scalp hair thinning, including occipital areas Scarring of the scalp or any other condition or disease of the scalp or hair, including diseases of the hair shaft (e.g., uncontrolled seborrheic dermatitis, tinea infections, other causes of alopecia, prior hair transplants or scalp reductions, psoriatic dermatitis) and inability to discontinue use of hair weaving. Subjects who use hair colourants/hair dyes, or have the remaining traces of colourants in their hair. Subjects must maintain their natural hair colour throughout the study. Hair length in non-balding areas ≤2cm (3/4 inch) around the vertex region of the head. Subjects must maintain the same hairstyle throughout the study. History of malignancy within the past five years, except basal cell or squamous cell carcinoma of the skin Serum PSA level > 2.0 ng/ml at screening visit. Family history(Father, brothers) of prostate cancer. Active unstable thyroid disease, including subjects on therapy for either hyperthyroidism or hypothyroidism unless their dose of thyroid medication has been stable for 3 months and serum TSH is normal Hypersensitivity to any 5 AR inhibitor or drugs chemically related to the study medication Use of finasteride or other 5 AR inhibitors within the 12 months prior to screening. Previous use of dutasteride. Use of phytotherapy (e.g. saw palmetto) within 8 weeks prior to screening. Previous use of cytotoxic agents Use of glucocorticoids (inhaled glucocorticoids are allowed; topical steroids are allowed provided that they are not used on the scalp) within the 3 months prior to screening Use of the following during the 6 months prior to screening: Minoxidil (oral or topical) Drugs with anti-androgenic properties (e.g., cyproterone acetate, spironolactone, ketoconazole, flutamide, bicalutamide). Cimetidine cannot be used during the study but is not an excluded drug when used during the previous 6 months. Topical estrogen, progesterone Tamoxifen Drugs potentially causing hypertrichosis (e.g., cyclosporine, diazoxide, phenytoin psoralens) Anabolic steroids Lithium and phenothiazines 17. Concurrent or regular use during the 4 weeks prior to screening of topical agents to the scalp (e.g., anti-inflammatories) 18. Participation in any investigational or marketed drug trial within 30 days preceding the screening phase of this study. Participation in any other drug trial during the course of this study including the follow-up period. 19. History or current evidence of drug or alcohol abuse within the 12 months prior screening 20. History of any illness (including psychiatric) which may impair the ability to provide informed consent or comply with study requirements 21. History of any unstable illness or condition that, in the opinion of the investigator, might confound the results or put the subject at risk. 22. Subjects who are known to be HIV positive (status which includes subjects with AIDS) 23. Subjects who will not refrain from donating blood until completing the study follow-up period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Dutasteride<br>Dutasteride | Drug: Dutasteride 0.5mg oral tablets<br>* Dutasteride<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Hair Growth Assessed by Macrophotographic Technique (Hair Count) in the Vertex at 6 Months. | The Macrophotographic hair count method marks a 1-inch diameter circular area at the anterior leading edge of the vertex thinning area and then photographed. The photographs are enlarged and converted into dot maps and the dot maps are converted into total hair counts by means of personal computer-based scanners and imaging software. | Baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline Hair Growth Assessed by Macrophotographic Technique (Hair Count) in the Vertex at 3 Months. | The Macrophotographic hair count method marks a 1-inch diameter circular area at the anterior leading edge of the vertex thinning area and then photographed. The photographs are enlarged and converted into dot maps and the dot maps are converted into total hair counts by means of personal computer-based scanners and imaging software. | Baseline and Month 3 | 
| Subjects Global Assessment of Hair Regrowth Question: Since the Start of Treatment I Have Lost? | GlaxoSmithKline - Hair Growth Index without Photographs subject assessment of change in hair loss and overall appearance at 3 and 6 months. Subjects answered 4 questions without photographs concerning their perception of Change in Hair Growth. | Month 3 and Month 6 | 
| Subjects Global Assessment of Hair Regrowth Question: Since the Start of Treatment my Usual Hair Loss Has Slowed Down? | GlaxoSmithKline - Hair Growth Index without Photographs subject assessment of change in hair loss and overall appearance at 3 and 6 months. Subjects answered 4 questions without photographs concerning their perception of Change in Hair Growth. | Month 3 and Month 6 | 
| Subjects Global Assessment of Hair Regrowth Question: Since Start of Treatment the Overall Appearance (Thickness, Hair Quality, Amount) of the Hair on my Head is? | GlaxoSmithKline - Hair Growth Index without Photographs subject assessment of change in hair loss and overall appearance at 3 and 6 months. Subjects answered 4 questions without photographs concerning their perception of Change in Hair Growth. | Month 3 and Month 6 | 
| Subjects Global Assessment of Hair Regrowth Question: Since the Start of Treatment I Have Kept What Hair I Had? | GlaxoSmithKline - Hair Growth Index without Photographs subject assessment of change in hair loss and overall appearance at 3 and 6 months. Subjects answered 4 questions without photographs concerning their perception of Change in Hair Growth. | Month 3 and Month 6 | 
| Subjects Global Assessment of Hair Regrowth Question: Since the Start of Treatment, When I Look at my Thinning Area, I Can See? | GlaxoSmithKline - Hair Growth Index with Photographs subject assessment of change in hair loss and overall appearance at 3 and 6 months. Subjects answered 4 questions comparing photographs of their hair before treatment and concerning the last week and evaluated the change in Hair Growth. | Month 3 and Month 6 | 
| Subjects Global Assessment of Hair Regrowth Question: Since the Start of Treatment my Hair Now Covers? | GlaxoSmithKline - Hair Growth Index with Photographs subject assessment of change in hair loss and overall appearance at 3 and 6 months. Subjects answered 4 questions comparing photographs of their hair before treatment and concerning the last week and evaluated the change in Hair Growth. | Month 3 and Month 6 | 
| Subjects Global Assessment of Hair Regrowth Question: Since the Start of Treatment the Amount of Hair on my Thinning Area Has? | GlaxoSmithKline - Hair Growth Index with Photographs subject assessment of change in hair loss and overall appearance at 3 and 6 months. Subjects answered 4 questions comparing photographs of their hair before treatment and concerning the last week and evaluated the change in Hair Growth. | Month 3 and Month 6 | 
| Subjects Global Assessment of Hair Regrowth Question: Since the Start of Treatment the Appearance (Thickness, Hair Quality, Amount) of the Thinning Area on my Head is? | GlaxoSmithKline - Hair Growth Index with Photographs subject assessment of change in hair loss and overall appearance at 3 and 6 months. Subjects answered 4 questions comparing photographs of their hair before treatment and concerning the last week and evaluated the change in Hair Growth. | Month 3 and Month 6 | 
| Investigator's Photographic Assessment of Improvement Distribution From Baseline | Improvement Distribution is based on the number of hairs per centimeters squared by macrophotographic conversion hair count. Score Range -3=greatly decreased to +3=greatly increased. 0=No change. | Month 3 and Month 6 | 
| Investigator's Photographic Assessment of Improvements From Baseline Score | Improvement Distribution Score is based on the number of hairs per centimeters squared by macrophotographic conversion hair count. Score Range: -3 = greatly decreased to +3 = greatly increased. 0 = No change. | Month 3 and Month 6 | 
| Panel Assessment of Improvement Distribution From Screening | Improvement Distribution is based on the number of hairs per centimeters squared by macrophotographic conversion hair count. Score Range -3=greatly decreased to +3=greatly increased. 0=No change. | Baseline to Month 3 and Baseline to Month 6 | 
| The Percentage Change From Baseline in Dihydrotestosterone (DHT) at Month 3, 6, and 10 | Mean percent change from Baseline for DHT. DHT was measured in pg/ml. Change from baseline = Month 3, 6, and 10 values minus baseline value. | Month 3, Month 6 and Month 10 | 
| The Percentage Change From Baseline in Testosterone at Month 3, 6, and 10 | Mean percent change from Baseline for testosterone. Testosterone was measured in ng/ml. | Month 3, Month 6, and Month 10 | 
| Endocrinology Shifts in Thyroid Stimulating Hormone (TSH), Thyroxine (T4), Prostate Specific Antigen (PSA), DHT, Testosterone (T), and Luteinizing Hormone (LH) From Baseline to Month 6 and Month 10. | Normal ranges: TSH, 0.25-3.50 µIU/mL; T4, 4.5-12.0 mg/dL; PSA, ≤4 ng/mL; DHT, males (m): prepuberty, <0.1, adult, 0.25-0.75; females (f): prepuberty, <0.03, premenopausal, 0.05-0.3, menopausal, <0.03 ng/mL; T, m: 2.36-9.96; f: 0.08-0.86 ng/mL; LH, m: 1-8; f: follicular, 4-12; periovulatory, >20; luteal 5-20; postmenopausal, >10 IU/L. | Baseline to Month 6 and Month 10 | 
| Laboratory Values: Electrolytes Assessed at Baseline and 6 Months. | Sodium, Potassium (mEq/L), and Bicarbonate | Baseline and Month 6 | 
| Laboratory Values: Hematology Assessed at Baseline and 6 Months. | Comparing Lab values and differences from Baseline to month 6 | Baseline and Month 6 | 
| Laboratory Values: Liver Enzymes Assessed at Baseline and 6 Months. | sGOT (AST)- serum Glutamic-Oxaloacetic Transaminase, sGPT (ALT) - serum Glutamic-Pyruvic Transaminase, Alkaline Phosphatase, Bilirubin(mg/dL) and Albumin(g/dL) | Baseline and Month 6 | 
| Laboratory Values: Other Chemistry Assessed at Baseline and 6 Months. | Glucose, Creatinine, Ferritine (ug/L) and Zinc (Hmol/L) | Baseline and Month 6 | 
| Sexual Function Inventory - Screening - Sex Drive, Erection, and Ejaculation | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? | Screening | 
| Sexual Function Inventory - Baseline - Sex Drive, Erection, and Ejaculation | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? | Baseline | 
| Sexual Function Inventory - Month 3 - Sex Drive, Erection, and Ejaculation | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? | Month 3 | 
| Sexual Function Inventory - Month 6 - Sex Drive, Erection, and Ejaculation | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? | Month 6 | 
| Sexual Function Inventory - Month 10 - Sex Drive, Erection, and Ejaculation | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? | Month 10 | 
| Sexual Function Inventory: Shifts From Baseline to Month 6 in Sex Drive | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? For example, No Problem shift to No Problem indicates that the participant experienced no problem at baseline and no problem at Month 6, respectively. | Baseline to Month 6 | 
| Sexual Function Inventory: Shifts From Baseline to Month 6 - Erection | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? For example, No Problem shift to No Problem indicates that the participant experienced no problem at baseline and no problem at Month 6, respectively. | Baseline to Month 6 | 
| Sexual Function Inventory: Shifts From Baseline to Month 6 - Ejaculation | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? For example, No Problem shift to No Problem indicates that the participant experienced no problem at baseline and no problem at Month 6, respectively. | Baseline to Month 6 | 
| Sexual Function Inventory: Shifts From Baseline to Month 10 in Sex Drive | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? For example, No Problem shift to No Problem indicates that the participant experienced no problem at baseline and no problem at Month 6, respectively. | Baseline to Month 10 | 
| Sexual Function Inventory: Shifts From Baseline to Month 10 - Erection | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? For example, No Problem shift to No Problem indicates that the participant experienced no problem at baseline and no problem at Month 6, respectively. | Baseline to Month 10 | 
| Sexual Function Inventory: Shifts From Baseline to Month 10 - Ejaculation | In the past 7 days, to what extent have you considered: a lack of sex drive to be a problem?, your ability to get and keep erections to be a problem? your ejaculation to be a problem? For example, No Problem shift to No Problem indicates that the participant experienced no problem at baseline and no problem at Month 6, respectively. | Baseline to Month 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dutasteride, Androgenic alopecia, phase 3