Study ARI114264: A Long-Term Study of the Safety and Efficacy of Dutasteride in the Treatment of Male Subjects With Androgenetic Alopecia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Dutasteride Arm
Subjects will receive 1 capsule of Dutasteride 0.5 mg orally once daily for 52 weeks (12 months).
干预措施: Dutasteride 0.5 mg (Drug)
结局指标
主要结局
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
时间窗: From Baseline (Week 0) until Week 52
An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign(including an abnormal laboratory finding), symptom, or disease(new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect, important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, drug-induced liver injury, breast cancer in male participants, prostate cancer, spontaneous abortion in female partner of male participants
Mean Change From Baseline in Hemoglobin, Albumin and Total Protein at the Indicated Time Points
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples were collected for the measurement of hemoglobin, albumin and total protein at Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. Change from Baseline in the hemoglobin, albumin and total protein values are summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Number of Participants With Any Laboratory Value Shifts From Baseline at Any Time Post-baseline
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples for the assessment of the indicated laboratory parameters were taken at the Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. The laboratory parameters included ALP, ALT, AST, total bilirubin, total protein, sodium, potassium, albumin, glucose, creatinine, urea/BUN, hemoglobin, hematocrit, red blood cell (RBC) count, platelet count, white blood cell (WBC) count, and prostate-specific antigen (PSA). A laboratory value (LV) that is within the normal range is considered normal. A LV that is above the upper limit of the normal range is considered high abnormal. A LV that is below the lower limit of the normal range is considered low abnormal. Number of participants with any LV shifts from BL at any time post-BL are presented for, normal at BL to abnormal; normal at BL to high; normal at BL to low; normal or low at BL to high; normal or high at BL to low.
Mean Change From Baseline in Heart Rate at the Indicated Time Points
时间窗: Baseline visit, Weeks 13, 26, 39, and 52 visits and or early withdrawal visit
Vital sign monitoring included heart rate measurement at the Screening visit, Baseline visit, Weeks 13, 26, 39, and 52 visits and the early withdrawal visit if applicable. Change from Baseline in heart rate is summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Number of Participants With Drug-related, Treatment-emergent AEs and AE Leading to Premature Study Drug Discontinuation and Possible Suicidality-related Adverse Event (PSRAE)
时间窗: From Baseline (Week 0) until Week 52
An AE is considered drug-related if the relationship variable indicates so, or if the variable value is missing. Any AE with a start date on or after the treatment start date and on or before the last dose of treatment is considered on-treatment (treatment-emergent). This includes an AE with a missing onset date. Any AE which occurred, in the investigator's judgement and is possibly related to suicidality, is defined as possible suicidality-related adverse event (PSRAE). Suicidality was assessed by using the columbia-suicide severity rating scale (C-SSRS) as determined by the investigator. The C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors.
Number of Participants With Change From Baseline in Breast Examination Results Any Time Post-Baseline Visit
时间窗: Baseline to Week 52
A qualitative breast examination was performed at Baseline (Week 0), at the Week 26 Visit and at the Week 52 Visit (and at the early withdrawal visit, if applicable). Participants were assessed for presence (reported as yes) and absence (reported as no) of palpable breast tissue (PBT) or nipple tenderness (NT) and/or clinically significant (CS) PBT or NT at Baseline (BL), at each scheduled Post-BL assessment. Change from BL in breast examination results included the number of participants with change from 'no (N)' at BL to 'yes (Y)' at any Post-BL assessment for the presence of PBT or NT, and the number of participants with change from N at BL in CS to Y at any Post-BL assessment in CS for PBT and for NT. BL value of an assessment is defined as the latest assessment on or before the BL date (latest non-missing value of either the treatment start date or the randomization date).
Mean Change From Baseline in Platelet Count and White Blood Cell Count at the Indicated Time Points
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples were collected for the measurement of platelet count and white blood cell count at Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. Change from Baseline in the platelet count and white blood cell count values are summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Mean Change From Baseline in Red Blood Cells Count at the Indicated Time Points
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples were collected for the measurement of the red blood cell count at Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. Change from Baseline in the red blood cell count value is summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Mean Change From Baseline in Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST) at the Indicated Time Points
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples were collected for the measurement of ALT, ALP and AST at Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. Change from Baseline in the ALT, ALP and AST values are summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Mean Change From Baseline in Hematocrit at the Indicated Time Points
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples were collected for the measurement of hematocrit at Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. Change from Baseline in the hematocrit value is summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Mean Change From Baseline in Total Bilirubin and Creatinine at the Indicated Time Points
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples were collected for the measurement of total bilirubin and creatinine at Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. Change from Baseline in the total bilirubin and creatinine values are summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Mean Change From Baseline in Potassium, Sodium, Glucose and Urea/Blood Urea Nitrogen (BUN) at the Indicated Time Points
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples were collected for the measurement of potassium, sodium, glucose and urea/BUN at Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. Change from Baseline in the potassium, sodium, glucose and urea/BUN values are summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Mean Change From Baseline in Prostate-specific Antigen at the Indicated Time Points
时间窗: Baseline, Week 26 and 52 visits and/or early withdrawal visit
Blood samples were collected for the measurement of prostate-specific antigen at Baseline, Week 26 and Week 52 visits and the early withdrawal visit where applicable. Change from Baseline in the prostate-specific antigen value is summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points
时间窗: Baseline, Weeks 13, 26, 39, and 52 visits and or early withdrawal visit
Blood pressure measurements were taken to observe vital signs and included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the Screening visit, Baseline visit, Weeks 13, 26, 39, and 52 visits and the early withdrawal visit if applicable. Change from Baseline in SBP and DBP is summarized for each post-Baseline assessment as well as for the final assessment (the last post-Baseline value in the study \[final value\]). Change from Baseline was calculated as the post-Baseline value minus the Baseline value. The Baseline value of an assessment is defined as the latest assessment on or before the Baseline date (latest non-missing value of either the treatment start date or the randomization date).
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: Baseline, Week 26 and Week 52
The C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. The number of participants answering yes/no responses to questions about suicidal ideation (Question \[Que\] 1 and Que 2) at Baseline and post-Baseline (since last visit) and suicidal behaviors (Que 6 - Que 10) at post-Baseline (since last visit) are presented. Questions included the presence (yes) or absence (no) of the following: Que 1 - a wish to be dead; Que 2 - nonspecific (NS) active suicidal thoughts; Que 6 - preparatory acts or behavior; Que 7 - aborted attempt; Que 8 - interrupted attempt (int. att.); Que 9 - non-fatal actual suicide attempt; Que 10 - completed suicide and non-suicidal self-injurious behavior. Final assessment (FA) is the last post-Baseline measurement during the study.
次要结局
- Mean Change From Baseline (BL) in Target Area Hair Count Within a 2.54 Centimeter (cm) Diameter Circle at Week 26 and Week 52(Baseline, Week 26, and Week 52)
- Mean Change From Baseline (BL) in Target Area Hair Width Within a 2.54 cm Diameter Circle at Week 26 and Week 52(Baseline, Week 26, and Week 52)
- 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(Baseline, Week 13, Week 26, Week 39 and Week 52)
- 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(Baseline, Week 26 and Week 52)
- Mean of Median Score for Panel Global Assessment of Improvement From Baseline to 26 Weeks and 52 Weeks for Vertex and Frontal Views(Baseline, Week 26 and Week 52)
- 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(Baseline, Week 13, Week 26, Week 39, and Week 52)
- Serum Concentrations of Dihydrotestosterone (DHT) at Baseline, and After 26 Weeks and 52 Weeks(Baseline, Week 26 and Week 52)
- Mean Change From Baseline (BL) in Terminal Hair Count Within a 2.54 cm Diameter Circle at Week 26 and Week 52(Baseline, Week 26 and Week 52)