Dutasteride Versus Placebo and Finasteride in Men With Androgenetic Alopecia

Study Overview
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Brief Summary
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The purpose of this six month study is to show that dutasteride is safe and more effective than placebo, and at least as safe and effective as finasteride in treating hair loss in men with androgenetic alopecia. Three doses of dutasteride will be investigated.

Detailed Description
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Androgenetic alopecia is a common, androgen-induced, pattern of progressive loss of scalp hair with an onset at any age after puberty in genetically predisposed people. The influence of androgens on scalp hair growth is mediated by local and systemic conversion of testosterone to dihydrotestosterone , by the enzyme 5 alpha-reductase. 5 alpha-reductase has been shown to exist as 2 isoenzyme forms, Type 1 and Type 2. Type 1 is predominantly located in the skin, both in the hair follicles and sebaceous glands, and is also found in the liver and kidney . Type 2 is the dominant form in male genitalia, including the prostate, although it has also been reported to be present in the inner root sheath of the hair follicle. The presence of both isoenzymes in the hair follicles suggests that both forms are likely to be important in the pathogenesis and treatment of androgenetic alopecia. Inhibition of both Type 1 and Type 2 5 alpha-reductase may be expected to more effectively reduce systemic and local dihydrotestosterone levels than inhibition of either isoenzyme alone. Finasteride is a selective Type 2 5 alpha-reductase inhibitor that is currently the only approved oral treatment for androgenetic alopecia worldwide. Dutasteride inhibits both Type 1 and Type 2 5alpha-reductase and is approved in more than 80 countries for the treatment of benign prostatic hyperplasia, and in Korea for the treatment of hair loss. Dutasteride is approximately 3 times as potent as finasteride at inhibiting Type 2 5 alpha-reductase and more than 100 times as potent at inhibiting Type 1 5 alpha-reductase. In a Phase II double-blind, placebo-controlled clinical study (ARIA2004) conducted in the United States, dutasteride demonstrated significant increases in target area hair count, as compared with placebo, as early as 12 weeks. In a Phase III double- blind, placebo-controlled clinical study conducted in Korea, dutasteride 0.5 milligram (mg) demonstrated significant increases in target area hair count, as compared with placebo, at 24 weeks. This 6 month study is being conducted to provide additional evidence of the efficacy and safety of three doses of dutasteride (0.02, 0.1 and 0.5mg) in the treatment of androgenetic alopecia, and more specifically, to characterize the dose-response relationship in an ethnically-diverse population. Treatment arms will be equally balanced with approximately 180 per arm.

Official Title
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A Study of the Efficacy and Safety of Multiple Doses of Dutasteride Versus Placebo and Finasteride in the Treatment of Male Subjects With Androgenetic Alopecia

Conditions
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Androgenetic Alopecia

Intervention / Treatment
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* Drug: 1mg Finasteride active
* Drug: 0.02mg dutasteride
* Drug: 0.1mg dutasteride
* Drug: 0.5mg dutasteride
* Drug: Finasteride placebo
* Drug: Dutasteride placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Norwood-Hamilton Type III vertex, IV, or V Exclusion Criteria: History or evidence of hair loss other than androgenetic alopecia Scarring of the scalp Use of dutasteride in previous 18 months Use of finasteride within previous 12 months Hair transplantation or hair weaving within 6 months Use of Minoxidil within previous 6 months Use of drugs with anti-androgenetic/androgenetic properties within previous 6 months Use of Drugs that cause hypertrichosis or hypotrichosis within previous 6 months Light or laser treatment of scalp within previous 3 months Cosmetic products aimed at improving or correcting signs of hair loss within previous 2 weeks

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 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 |
| --- | --- |
| Active Comparator: 1mg Finasteride<br>1mg finasteride active plus dutasteride placebo, by mouth once daily | Drug: 1mg Finasteride active<br>* 1mg finasteride active, by mouth once daily<br>Drug: Dutasteride placebo<br>* dutasteride placebo, by mouth once daily<br>|
| Active Comparator: 0.02mg Dutasteride<br>0.02mg dutasteride active plus finasteride placebo, by mouth once daily | Drug: 0.02mg dutasteride<br>* 0.02mg dutasteride active, by mouth once daily<br>Drug: Finasteride placebo<br>* finasteride placebo, by mouth once daily<br>|
| Active Comparator: 0.1mg Dutasteride<br>0.1mg dutasteride active plus finasteride placebo, by mouth once daily | Drug: 0.1mg dutasteride<br>* 0.1mg dutasteride active, by mouth once daily<br>Drug: Finasteride placebo<br>* finasteride placebo, by mouth once daily<br>|
| Active Comparator: 0.5mg Dutasteride<br>0.5mg dutasteride active plus finasteride placebo, by mouth once daily | Drug: 0.5mg dutasteride<br>* 0.5mg dutasteride active, by mouth once daily<br>Drug: Finasteride placebo<br>* finasteride placebo, by mouth once daily<br>|
| Placebo Comparator: Placebo<br>1mg finasteride placebo plus dutasteride placebo, by mouth once daily | Drug: Finasteride placebo<br>* finasteride placebo, by mouth once daily<br>Drug: Dutasteride placebo<br>* dutasteride placebo, by mouth once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (BL) in Target Area Hair Count (HC) Within a 2.54 Centimeter (cm) (1 Inch) Diameter Circle at the Vertex at Week 24, as Assessed by Macrophotographic Technique (MT) | The primary target area HC was based on the nonvellus hair (>=30 micrometers [μm] in width; thick and noticeable hair) count within a target 2.54 cm (1 inch) diameter circle at the vertex (crown, topmost part of the head). A cosmetic ink dot was placed by tattoo at BL so that the same area could be identified at BL and post-BL. If the ink dot faded, it was re-done in exactly the same location to ensure visibility for subsequent photographs. For the MT, hair was clipped before each photograph; HC was based on hair follicles in the photographs. Change from BL=Week 24 value minus the BL value. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Target Area Hair Count Within a 1.13 cm (0.44 Inch) Diameter Circle at the Vertex at Week 24, as Assessed by MT | The primary target area HC was based on the nonvellus hair (>=30 micrometers [μm] in width; thick and noticeable hair) count within a target 1.13 cm (0.44 inch) diameter circle at the vertex (crown, topmost part of the head). A cosmetic ink dot was placed by tattoo at BL so that the same area could be identified at BL and post-BL. If the ink dot faded, it was re-done in exactly the same location to ensure visibility for subsequent photographs. For the MT, hair was clipped before each photograph; HC was based on hair follicles in the photographs. Change from BL=Week 24 value minus the BL value. | Baseline and Week 24 | 
| Change From Baseline in Target Area Hair Count Within a 2.54 cm (1 Inch) Diameter Circle at the Vertex at Week 12 as Assessed by MT | The primary target area HC was based on the nonvellus hair (>=30 micrometers [μm] in width; thick and noticeable hair) count within a target 2.54 cm (1 inch) diameter circle at the vertex (crown, topmost part of the head). A cosmetic ink dot was placed by tattoo at BL so that the same area could be identified at BL and post-BL. If the ink dot faded, it was re-done in exactly the same location to ensure visibility for subsequent photographs. For the MT, hair was clipped before each photograph; HC was based on hair follicles in the photographs. Change from BL=Week 12 value minus the BL value. | Baseline and Week 12 | 
| Change From Baseline in Target Area Hair Count Within a 1.13 cm (0.44 Inch) Diameter Circle at the Vertex, as Assessed by MT at Week 12 | The primary target area HC was based on the nonvellus hair (>=30 micrometers [μm] in width; thick and noticeable hair) count within a target 1.13 cm (0.44 inch) diameter circle at the vertex (crown, topmost part of the head). A cosmetic ink dot was placed by tattoo at BL so that the same area could be identified at BL and post-BL. If the ink dot faded, it was re-done in exactly the same location to ensure visibility for subsequent photographs. For the MT, hair was clipped before each photograph; HC was based on hair follicles in the photographs. Change from BL=Week 12 value minus the BL value. | Baseline and Week 12 | 
| Change From Baseline in Target Area Hair Width Within a 2.54 cm (1 Inch) Diameter Circle at the Vertex at Week 12 and Week 24, as Assessed by MT | The target area hair width was the sum of all nonvellus hairs (>=30 µm in width; thick and noticeable hair) within a target 2.54 cm (1 inch) diameter circle at the vertex (crown, topmost part of the head). For the MT, hair was clipped before each photograph. A cosmetic ink dot was placed by tattoo at Baseline so that the same area could be identified at Baseline and post-Baseline. If the ink dot faded, it was re-done in exactly the same location to ensure it was visible for subsequent photographs. Change from Baseline was calculated as the Week 12 or Week 24 value minus the Baseline value. | Baseline, Week 12, and Week 24 | 
| Change From Baseline in Target Area Hair Width Within a 1.13 cm (0.44 Inch) Diameter Circle at the Vertex at Week 12 and Week 24, as Assessed by MT | The target area hair width was the sum of all nonvellus hairs (>=30 µm in width; thick and noticeable hair) within a target 1.13 cm (0.44 inch) diameter circle at the vertex (crown, topmost part of the head). For the MT, hair was clipped before each photograph. A cosmetic ink dot was placed by tattoo at Baseline so that the same area could be identified at Baseline and post-Baseline. If the ink dot faded, it was re-done in exactly the same location to ensure it was visible for subsequent photographs. Change from Baseline was calculated as the Week 12 or Week 24 value minus the Baseline value. | Baseline, Week 12, and Week 24 | 
| Change From Baseline in Terminal Hair Count (THC) Within a 2.54 cm (1 Inch) Diameter Circle at the Vertex at Week 12 and Week 24, as Assessed by MT | The THC (thick, long, and dark hair) was the sum of all nonvellus hairs (>=60 μm in width; thick and noticeable hair) within a target 2.54 cm (1 inch) diameter circle at the vertex (crown, topmost part of the head). A cosmetic ink dot was placed by tattoo at BL so that the same area could be identified at BL and post-BL. If the ink dot faded, it was re-done in exactly the same location to ensure visibility for subsequent photographs. For the MT, hair was clipped before each photograph; HC was based on the hair follicles in the photographs. Change from BL=Week 12/Week 24 value minus BL value. | Baseline, Week 12, and Week 24 | 
| Change From Baseline in Terminal Hair Count Within a 1.13 cm (0.44 Inch) Diameter Circle at the Vertex at Week 12 and Week 24, as Assessed by MT | The THC (thick, long, and dark hair) was the sum of all nonvellus hairs (>=60 μm in width; thick and noticeable hair) within a target 1.13 cm (0.44 inch) diameter circle at the vertex (crown, topmost part of the head). A cosmetic ink dot was placed by tattoo at BL so that the same area could be identified at BL and post-BL. If the ink dot faded, it was re-done in exactly the same location to ensure visibility for subsequent photographs. For the MT, hair was clipped before each photograph; HC was based on hair follicles in the photographs. Change from BL=Week 12/Week 24 value minus BL value. | Baseline, Week 12, and Week 24 | 
| Global Assessment of Improvement From Baseline to Week 24 Assessed for Vertex and Frontal Views Separately | A central panel of 3 dermatologists independently assessed change in hair growth from Baseline to Week 24 using a 7-point scale: greatly decreased (-3), moderately decreased (-2), slightly decreased (-1), no change (0), slightly increased (1), moderately increased (2), and greatly increased (3). The median score, across the 3 panel members, is summarized. This assessment was performed by comparing the global photographs obtained at Baseline with those subsequently obtained at Week 24. This assessment was made separately based on the global photography of the vertex and frontal views. | Baseline and Week 24 | 
| Change From Baseline in Investigator Photographic Assessment Questionnaire (IPAQ) Scores Assessed at Week 12 for Vertex and Frontal Views Separately | The IPAQ was completed by the Investigator or designee by comparing the global photographs obtained at Baseline with those obtained at Week 12. This assessment was made separately based on the global photography of the vertex and frontal views. 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. | Baseline and Week 12 | 
| Change From Baseline in Investigator Photographic Assessment Questionnaire (IPAQ) Scores Assessed at Week 24 for Vertex and Frontal Views Separately | The IPAQ was completed by the Investigator or designee by comparing the global photographs obtained at Baseline with those obtained at Week 12. This assessment was made separately based on the global photography of the vertex and frontal views. 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. | Baseline and Week 24 | 
| Number of Participants With the Indicated Change From Baseline (BL) in the Stage (S) of Androgenic Alopecia (AGA) According to the Norwood-Hamilton Scale at Week 12 (W12) | The investigator/designee assessed the stage (Stage I to Stage VII) of AGA (i.e., male pattern baldness [MPB]) by utilizing the Norwood-Hamilton scale, used to measure the progression of MPB. Stage VII indicates worse balding than stage I. Assessment was made by direct visual examination (aided by pictures) of the participant at Baseline and Week 12 (W12). v, vertex; most of the hair loss (commonly seen with advancing age) is on the vertex. a, type a variant; major features are (1) the entire anterior hairline border recedes in unison; (2) there is no simultaneous balding of the vertex. | Baseline and Week 12 | 
| Number of Participants With the Indicated Change From Baseline (BL) in the Stage (S) of Androgenic Alopecia (AGA) According to the Norwood-Hamilton Scale at Week 24 | The investigator/designee assessed the stage (Stage I to Stage VII) of AGA (i.e., male pattern baldness [MPB]) by utilizing the Norwood-Hamilton scale, used to measure the progression of MPB. Stage VII indicates worse balding than stage I. Assessment was made by direct visual examination (aided by pictures) of the participant at Baseline and Week 24 (W24). v, vertex; most of the hair loss (commonly seen with advancing age) is on the vertex. a, type a variant; major features are (1) the entire anterior hairline border recedes in unison; (2) there is no simultaneous balding of the vertex. | Baseline and Week 24 | 
| Serum Concentration of Dutasteride at Week 12, Week 24, and Follow-up (Week 26) | Serum concentrations of dutasteride were measured after 12 weeks and 24 weeks of study treatment and at follow-up (approximately 2 weeks after the last dose of study treatment). | Week 12, Week 24, and Week 26 | 
| Serum Dihydrotestosterone (DHT) at Week 12, Week 24, and Follow-up (Week 26) | Serum concentrations of DHT were measured after 12 weeks and 24 weeks of study treatment and at follow-up (approximately 2 weeks after the last dose of study treatment). | Week 12, Week 24, and Week 26 | 
| Change From Baseline in Hair Growth Index (HGI) Scores at Weeks 12 and 24 | Participant-perceived change in HG was assessed by 3 questions (each scored on a 7-point scale) on a health outcome questionnaire: Since the start of treatment, when I look at my thinning area, I can see..., Since the start of treatment, my hair now covers…, and Since the start of treatment, the appearance (thickness/quality/amount) of the thinning area on my head is… -3, Much less; -2, Moderately less; -1, Slightly less; 0, The same amount; 1, Slightly more; 2, Moderately more; 3, Much more scalp. The scores for the 3 questions were summed to obtain the HGI total score (-9 to 9). | Baseline, Week 12, and Week 24 | 
| Change From Baseline in Total Hair Growth Satisfaction Scale (HGSS) Scores at Weeks 12 and 24 | Participant satisfaction with hair appearance/growth was assessed by 5 questions (each scored on a 7-point scale: How satisfied do you feel about: [1] The overall appearance of your hair; [2] The appearance of the thinning area[s] [TAs] on your head; [3] The amount of scalp that can be seen in the TAs; [4] The amount of hair in the TAs; [5] The growth of hair in the TAs): -3, Very dissatisfied (DS); -2, DS; -1, Somewhat DS; 0, Neutral (neither satisfied nor DS); 1, Somewhat satisfied (SA); 2, SA; 3, Very SA. The scores for the 5 questions were summed to obtain the HGSS total score (-15 to 15). | Baseline, Week 12, and Week 24 |