Clinical trial NCT01831791: A Long-term Study to Determine Safety and Efficacy of Dutasteride in Male Subjects With Androgenetic Alopecia
Official title: Study ARI114264: A Long-Term Study of the Safety and Efficacy of Dutasteride in the Treatment of Male Subjects With Androgenetic Alopecia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alopecia
Keywords: male pattern hair loss
hair growth
hair restoration
Dutasteride
Androgenetic alopecia
safety
efficacy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-04-15
Enrollment: 120
Sex: MALE
Minimum age (years): 20
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicentre, open-label study to assess the safety, tolerability, and efficacy of 0.5 mg Dutasteride administered once daily for 52 weeks in men with Androgenetic Alopecia types III vertex, IV and V per the Norwood-Hamilton classification. The study consists of a Screening Phase (3 weeks prior to Baseline) and a Treatment Phase (52 weeks). A subject who completes the full course of study treatment and the final study visit (Week 52; Visit 7) will be considered as study completion.


Eligibility criteria: Inclusion Criteria:

* Male outpatient, 20 to 50-years-old, inclusive (at the time of obtaining consent).
* AGA classified as Type III vertex, IV, or V (excluding Type IV anterior and V anterior) utilizing the Norwood-Hamilton classification.
* Fluent and literate in Japanese with the ability to comprehend and record information on the PAS SFI and DLQI questionnaires.
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2 x upper limit of normal (ULN); alkaline phosphatase and bilirubin \<=1.5 x ULN (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%).
* Willing to comply with study requirements, including maintaining the same hair color and hairstyle throughout the study- a) subjects who use hair colorants/hair dyes may continue to do so; however, there should be no traces of hair color remaining on the scalp at the time of study visits. b) hair length in nonbalding areas should be \>=2 cm (0.75 inch) around the vertex region of the head at the time of study visits.
* Able to swallow and retain oral medication

Exclusion Criteria:

* Evidence of hypogonadism defined as serum testosterone \<250 Nanogram/decilitre (ng/dl) at Screening.
* Unstable liver disease (chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria).
* History of renal insufficiency or Serum creatinine \>1.5 x ULN at Screening.
* History of malignancy within the past 5 years, except basal cell or squamous cell carcinoma of the skin.
* History of prostate cancer before the age of 50 years in a first degree relative.
* Serum PSA level \>2.0 nanogram/millilitre (ng/mL) at Screening.
* History of breast cancer or clinical breast examination suggestive of malignancy.
* Active unstable thyroid disease, including subjects on therapy for either hyperthyroidism or hypothyroidism unless their dose of thyroid medication has been stable for at least 3 months.
* Any unstable, serious co-existing medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to Screening; uncontrolled diabetes or peptic ulcer disease which is uncontrolled by medical management, and subjects who are known to be acquired immunodeficiency syndrome \[AIDS\](including subjects with a diagnosis of human immunodeficiency virus (HIV) positive).
* History or current evidence of any serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions that could, in the opinion of the investigator or GSK medical monitor, interfere with the subject's safety, obtaining informed consent, or compliance with study procedures. Note: the investigator may consult with GSK medical monitor if a condition could interfere with the subject's safety.
* Clinically relevant abnormal finding on the Screening electrocardiogram (ECG).
* Global scalp hair thinning, including occipital areas.
* Scarring of the scalp, including prior hair transplant or scalp reduction, or any other condition or disease of the scalp or hair, including diseases of the hair shaft (e.g., tinea infection, nonandrogenetic-cause of alopecia, psoriatic dermatitis or other psoriatic lesions, or uncontrolled seborrheic dermatitis).
* History of hair transplantation at any time to correct AGA or use of hair weaving within 6 months prior to Screening.
* History or evidence of hair loss other than AGA (e.g., due to an auto-immune, endocrine, mechanical or infectious process, or secondary to a scalp dermatological disorder).
* Use of any cosmetic product aimed at improving or correcting the signs of hair loss (e.g., scalp preparations with claims aiming at improved hair growth) within 2 weeks prior to Screening.
* Use of light or laser treatments on the scalp (e.g., light emitting diode \[LED\] lamps) within 3 months prior to Screening.
* Hypersensitivity to any 5 alpha-reductase (5AR) inhibitor or drugs chemically related to the study treatment.
* Use of Dutasteride within 18 months prior to Screening, or use of finasteride within 12 months prior to Screening.
* Previous use of systemic cytotoxic agents.
* Use of glucocorticoids (inhaled glucocorticoids are allowed; topical corticosteroids are allowed provided that they are not used on the scalp) within 3 months prior to Screening.
* Use of the following during the 6 months prior to Screening: Minoxidil (oral or topical), Carpronium chloride, Systemic drugs with anti-androgenic properties (e.g., cyproterone acetate, spironolactone, ketoconazole, flutamide, and bicalutamide). Use of ketoconazole shampoo on the scalp is prohibited during the study, but use before Screening is not a reason for exclusion. Cimetidine is prohibited during the study, but use before Screening is not a reason for exclusion, Topical estrogen or progesterone, Topical prostaglandin analogs on the scalp, Tamoxifen, Drugs potentially causing hypertrichosis (e.g., cyclosporine, diazoxide, phenytoin, psoralens), Drugs potentially causing hypotrichosis or telogen effluvium (e.g., valproic acid), Anabolic steroids, Lithium or phenothiazines.
* Participation in any investigational or marketed drug or device trial within 1 month prior to Screening for this study. Including participation in any trial for Dutasteride and administration of active drugs (Dutasteride or finasteride) prior to Screening for this study. In addition, subjects must not participate in any other drug or device trials during the course of this study.

Primary outcomes:
measure: Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
timeFrame: From Baseline (Week 0) until Week 52
measure: Number of Participants With Drug-related, Treatment-emergent AEs and AE Leading to Premature Study Drug Discontinuation and Possible Suicidality-related Adverse Event (PSRAE)
timeFrame: From Baseline (Week 0) until Week 52
measure: Number of Participants With Change From Baseline in Breast Examination Results Any Time Post-Baseline Visit
timeFrame: Baseline to Week 52
measure: Mean Change From Baseline in Hemoglobin, Albumin and Total Protein at the Indicated Time Points
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Mean Change From Baseline in Hematocrit at the Indicated Time Points
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Mean Change From Baseline in Platelet Count and White Blood Cell Count at the Indicated Time Points
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Mean Change From Baseline in Red Blood Cells Count at the Indicated Time Points
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Mean Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at the Indicated Time Points
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Mean Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Mean Change From Baseline in Potassium, Sodium, Glucose and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Mean Change From Baseline in Prostate-specific Antigen at the Indicated Time Points
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Number of Participants With Any Laboratory Value Shifts From Baseline at Any Time Post-baseline
timeFrame: Baseline, Week 26 and 52 visits and/or early withdrawal visit
measure: Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points
timeFrame: Baseline, Weeks 13, 26, 39, and 52 visits and or early withdrawal visit
measure: Mean Change From Baseline in Heart Rate at the Indicated Time Points
timeFrame: Baseline visit, Weeks 13, 26, 39, and 52 visits and or early withdrawal visit
measure: Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, Week 26 and Week 52
Secondary outcomes:
measure: Mean Change From Baseline (BL) in Target Area Hair Count Within a 2.54 Centimeter (cm) Diameter Circle at Week 26 and Week 52
timeFrame: Baseline, Week 26, and Week 52
measure: Mean Change From Baseline (BL) in Target Area Hair Width Within a 2.54 cm Diameter Circle at Week 26 and Week 52
timeFrame: Baseline, Week 26, and Week 52
measure: Mean Change From Baseline (BL) in Terminal Hair Count Within a 2.54 cm Diameter Circle at Week 26 and Week 52
timeFrame: Baseline, Week 26 and Week 52
measure: Mean of Median Score for Panel Global Assessment of Improvement From Baseline to 26 Weeks and 52 Weeks for Vertex and Frontal Views
timeFrame: Baseline, Week 26 and Week 52
measure: Number of Participants With the Indicated Change From Baseline (BL) in the Stage of Androgenic Alopecia (AGA) According to the Norwood-Hamilton Scale at 26 Weeks and 52 Weeks
timeFrame: Baseline, Week 26 and Week 52
measure: Change From Baseline in Sexual Problems as Assessed by the Problem Assessment Scale of the Sexual Function Inventory (PAS SFI) at Week 13, Week 26, Week 39, and Week 52
timeFrame: Baseline, Week 13, Week 26, Week 39 and Week 52
measure: Change From Baseline in Quality of Life as Assessed by Dermatology Life Quality Index (DLQI) at Week 13, Week 26, Week 39, and Week 52
timeFrame: Baseline, Week 13, Week 26, Week 39, and Week 52
measure: Serum Concentrations of Dihydrotestosterone (DHT) at Baseline, and After 26 Weeks and 52 Weeks
timeFrame: Baseline, Week 26 and Week 52
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tsunemi Y, Irisawa R, Yoshiie H, Brotherton B, Ito H, Tsuboi R, Kawashima M, Manyak M; ARI114264 Study Group. Long-term safety and efficacy of dutasteride in the treatment of male patients with androgenetic alopecia. J Dermatol. 2016 Sep;43(9):1051-8. doi: 10.1111/1346-8138.13310. Epub 2016 Feb 19.