Dutasteride Versus Placebo and Finasteride in Men With Androgenetic Alopecia

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

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.

Study Overview

• Status: Completed
• Conditions: Androgenetic Alopecia
• Intervention / Treatment: Drug: 1mg Finasteride active; Drug: Dutasteride placebo; Drug: 0.02mg dutasteride; Drug: Finasteride placebo; Drug: 0.1mg dutasteride; Drug: 0.5mg dutasteride

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 917
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1425
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1114AAP
    • GSK Investigational Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1055AAO
      • GSK Investigational Site
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1425BEA
      • GSK Investigational Site
    • La Boca, Buenos Aires, Argentina, C1155AHD
      • GSK Investigational Site
• Chile
  • Región Metro De Santiago
    • Santiago, Región Metro De Santiago, Chile, 7580206
      • GSK Investigational Site
  • Valparaíso
    • Viña del Mar, Valparaíso, Chile, 252 0000
      • GSK Investigational Site
• Japan
  • Fukuoka, Japan, 812-0025
    • GSK Investigational Site
  • Osaka, Japan, 530-0057
    • GSK Investigational Site
  • Osaka, Japan, 532-0003
    • GSK Investigational Site
  • Tokyo, Japan, 103-0028
    • GSK Investigational Site
  • Tokyo, Japan, 160-0022
    • GSK Investigational Site
• Mexico
  • Mexico City, Mexico, 03720
    • GSK Investigational Site
  • Mexico city, Mexico, 06780
    • GSK Investigational Site
  • Estado De México
    • Naucalpan, Estado De México, Mexico, 11200
      • GSK Investigational Site
  • Jalisco
    • Zapopan, Jalisco, Jalisco, Mexico, 45190
      • GSK Investigational Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • GSK Investigational Site
  • Sinaloa
    • Mazatlan, Sinaloa, Sinaloa, Mexico, 82126
      • GSK Investigational Site
• Peru
  • Lima, Peru, Lima 27
    • GSK Investigational Site
  • Lima Cercado, Peru, LIMA 01
    • GSK Investigational Site
  • Lima
    • Lima 41, Lima, Peru, Lima 41
      • GSK Investigational Site
• Philippines
  • Makati City, Philippines, 1200
    • GSK Investigational Site
  • Manila, Philippines, 1000
    • GSK Investigational Site
  • Quezon City, Philippines, 1113
    • GSK Investigational Site
  • Quezon City, Philippines
    • GSK Investigational Site
  • Tanauan City, Batangas, Philippines, 4232
    • GSK Investigational Site
• Russian Federation
  • Moscow,, Russian Federation, 107076
    • GSK Investigational Site
  • Nizhny Novgorod, Russian Federation, 603950
    • GSK Investigational Site
  • Ryazan, Russian Federation, 390046
    • GSK Investigational Site
  • St'Petersburg, Russian Federation, 192102
    • GSK Investigational Site
  • St-Petersburg, Russian Federation, 196084
    • GSK Investigational Site
• Taiwan
  • Tainan, Taiwan, 70403
    • GSK Investigational Site
  • Taipei, Taiwan
    • GSK Investigational Site
  • Taipei, Taiwan, 105
    • GSK Investigational Site
  • Taipei, Taiwan, 220
    • GSK Investigational Site
• Thailand
  • Bangkoknoi Bangkok, Thailand, 10700
    • GSK Investigational Site
  • Chiang Mai, Thailand, 50200
    • GSK Investigational Site
  • Patumwan Bangkok, Thailand, 10330
    • GSK Investigational Site
  • Rajthevee Bangkok, Thailand, 10400
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1mg Finasteride; 1mg finasteride active plus dutasteride placebo, by mouth once daily	Drug: 1mg Finasteride active; 1mg finasteride active, by mouth once daily; Drug: Dutasteride placebo; dutasteride placebo, by mouth once daily
Active Comparator: 0.02mg Dutasteride; 0.02mg dutasteride active plus finasteride placebo, by mouth once daily	Drug: 0.02mg dutasteride; 0.02mg dutasteride active, by mouth once daily; Drug: Finasteride placebo; finasteride placebo, by mouth once daily
Active Comparator: 0.1mg Dutasteride; 0.1mg dutasteride active plus finasteride placebo, by mouth once daily	Drug: Finasteride placebo; finasteride placebo, by mouth once daily; Drug: 0.1mg dutasteride; 0.1mg dutasteride active, by mouth once daily
Active Comparator: 0.5mg Dutasteride; 0.5mg dutasteride active plus finasteride placebo, by mouth once daily	Drug: Finasteride placebo; finasteride placebo, by mouth once daily; Drug: 0.5mg dutasteride; 0.5mg dutasteride active, by mouth once daily
Placebo Comparator: Placebo; 1mg finasteride placebo plus dutasteride placebo, by mouth once daily	Drug: Dutasteride placebo; dutasteride placebo, by mouth once daily; Drug: Finasteride placebo; finasteride placebo, by mouth once daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: October 28, 2010
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 28, 2012

Study Registration Dates

• First Submitted: October 28, 2010
• First Submitted That Met QC Criteria: October 28, 2010
• First Posted (Estimate): November 1, 2010

Study Record Updates

• Last Update Posted (Actual): August 10, 2018
• Last Update Submitted That Met QC Criteria: June 18, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Pathological Conditions, Anatomical; Hypotrichosis; Hair Diseases; Alopecia; Alopecia Areata; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Urological Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Steroid Synthesis Inhibitors; 5-alpha Reductase Inhibitors; Dutasteride; Finasteride
• Other Study ID Numbers: 114263

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 114263
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 114263
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: 114263
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 114263
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 114263
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 114263
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 114263
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No