Bioequivalence Study of Dutasteride Capsules-An Evaluation of the Bioequivalence of Dutasteride Capsule Manufactured at GSK Compared to Dutasteride Capsule Manufactured at Catalent in Healthy Japanese Male Subjects
概览
- 阶段
- 1 期
- 干预措施
- Dutasteride-Test product
- 疾病 / 适应症
- Prostatic Hyperplasia
- 发起方
- GlaxoSmithKline
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Maximal measured plasma concentration (Cmax) of dutasteride test product and reference product
- 状态
- 已完成
- 最后更新
- 7年前
概览
简要总结
This will be a single center, open-label, single dose, randomized and 2-way crossover study in healthy Japanese male subjects under fasting conditions. The study will be conducted to determine the bioequivalence between dutasteride capsules manufactured at GSK (test product) and dutasteride capsule manufactured at Catalent (reference product) in healthy Japanese male subjects. Subjects will have a screening visit within 30 days prior to the first dose of study treatment, two treatment periods separated by 28-days washout period, a re-visit 10-14 days after the second dose for the first follow-up and a second follow up via telephone 50-54 days after the second dose. The total duration of the study will be approximately 15 weeks from screening to the second follow up.
研究者
入排标准
入选标准
- •Between 20 and 64 years of age inclusive, at the time of signing the informed consent.
- •Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator in consultation with the Medical Monitor if required agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 18.5-24.9 kg/meter squared at screening.
- •Japanese male.
- •Male subjects with female partners of child bearing potential must comply with the contraception requirements from the time of first dose of study medication until the second follow-up.
- •Capable of giving signed informed consent as described in which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
排除标准
- •ALT and bilirubin \>1.5xupper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
- •Corrected QT interval (QTc) \>450 milliseconds (msec).
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •History of myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident.
- •History of diabetes or peptic ulcer disease which is uncontrolled by medical management.
- •History of breast cancer or clinical breast examination finding suggestive of malignancy.
- •History of malignancy within the past five years, except for basal cell carcinoma of the skin. Subjects with a prior malignancy who have had no evidence of disease for at least the past 5 years are eligible.
- •Prior medical history or evidence of prostate cancer (e.g., positive biopsy, or suspicious ultrasound, or suspicious digital rectal examination (DRE)). Patients with suspicious ultrasound or DRE who have had a negative biopsy within the preceding 6 months and stable prostate specific antigen (PSA) are eligible for the study.
- •Creatinine \>1.5xULN.
- •History or current conditions of drug abuse or alcoholism.
研究组 & 干预措施
Sequence 1-Dutasteride test product and then Reference product
Participants will receive treatment A in period 1 and treatment B in period 2. Where treatment A= dutasteride 0.5 mg capsule test product, treatment B= dutasteride 0.5 mg capsule reference product.
干预措施: Dutasteride-Test product
Sequence 1-Dutasteride test product and then Reference product
Participants will receive treatment A in period 1 and treatment B in period 2. Where treatment A= dutasteride 0.5 mg capsule test product, treatment B= dutasteride 0.5 mg capsule reference product.
干预措施: Dutasteride-Reference product
Sequence 2-Dutasteride reference product and then test product
Participants will receive treatment B in period 1 and treatment A in period 2. Where treatment A= dutasteride 0.5 mg capsule test product, treatment B= dutasteride 0.5 mg capsule reference product.
干预措施: Dutasteride-Test product
Sequence 2-Dutasteride reference product and then test product
Participants will receive treatment B in period 1 and treatment A in period 2. Where treatment A= dutasteride 0.5 mg capsule test product, treatment B= dutasteride 0.5 mg capsule reference product.
干预措施: Dutasteride-Reference product
结局指标
主要结局
Maximal measured plasma concentration (Cmax) of dutasteride test product and reference product
时间窗: Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period
Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours.
Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC 0-t) of dutasteride test product and reference product
时间窗: Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.
Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours.
次要结局
- Number of subjects with adverse events(Approximately 12 weeks)
- Change from Baseline in hematology parameters(Baseline (screening or Day-1) and Day 2 of each treatment period.)
- Change from Baseline in clinical chemistry parameters(Baseline (screening or Day-1) and Day 2 of each treatment period.)
- Change from Baseline in routine urinalysis parameters(Baseline (screening or Day-1) and Day 2 of each treatment period.)
- Change from Baseline in systolic and diastolic blood pressure measurements(Baseline (screening) and Day 1and Day 2 of each treatment period and at first follow-up visit (approximately up to 11 weeks).)
- Change from Baseline in pulse rate(Baseline (screening) and Day 1and Day 2 of each treatment period and at first follow-up visit (approximately up to 11 weeks).)
- Change from Baseline in electrocardiogram (ECG) parameters(Baseline (screening) and Day 1and Day 2 of each treatment period and at first follow-up visit (approximately up to 11 weeks).)
- Change from Baseline in body temperature(Baseline (screening) and Day 1and Day 2 of each treatment period and at first follow-up visit (approximately up to 11 weeks).)
- Area under the concentration-time curve from pre-dose to 24 hours (AUC[0-24]) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Area under the plasma concentration-time curve from time zero to infinity (AUC 0-infinity) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Time of the maximum plasma concentration (tmax) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Elimination rate constant (Kel) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Terminal half life (t1/2e) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Percentage of AUC0-infinity obtained by extrapolation (%AUCex) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Apparent clearance following oral dosing (CL/F) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Apparent volume of distribution after oral administration (Vz/F) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Mean residence time (MRT) of dutasteride test product and reference product(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)
- Correlation coefficient between time and log concentration of dutasteride for the points used in the estimation of kel.(Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period.)