An Open-label, Randomized, Single Dose, Two-Period Crossover Study to Determine the Bioavailability of a Fixed Dose Combination Capsule Formulation of Dutasteride and Tamsulosin Hydrochloride (0.5mg/0.2mg) Relative to Co-administration of Dutasteride 0.5mg Capsules and Tamsulosin Hydrochloride 0.2mg
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 86
- 试验地点
- 1
- 主要终点
- 1. To investigate the bioavailability of a combination capsule formulation of dutasteride 0.5 mg/ tamsulosin HCl 0.2 mg relative to concomitant dosing of dutasteride 0.5 mg capsules and tamsulosin 0.2 mg tablets in the fed and fasted states.
研究概览
简要总结
This study will be an open-label, randomized, single dose, two-period crossover study to determine the bioavailability of a fixed dose combination capsule formulation of dutasteride and tamsulosin hydrochloride (0.5mg/0.2mg) relative to co-administration of dutasteride 0.5mg capsules and tamsulosin hydrochloride 0.2mg tablets in healthy male subjects of North East Asian and non-Asian ancestry. Subjects will receive single oral doses of a combination capsule formulation of dutasteride 0.5 mg/ tamsulosin 0.2 mg in a fed or fasted state or concomitant dosing of dutasteride 0.5 mg and the Japan-sourced Harnal-D 0.2 mg in a fed or fasted state. Each dose of study medication will be separated by a 28-day washout period. Blood samples for pharmacokinetic analysis will be taken at regular intervals after dosing. Safety will be assessed by measurement of blood pressure, heart rate, safety laboratory data, and review of adverse events. The study will enrol 88 healthy male subjects to ensure that 80 complete the study. At least twenty percent of the study population will be of Japanese ancestry, approximately 20% will be of Chinese ancestry and approximately 20% of Korean ancestry while the remainder of the population will be of non-Asian ancestry.
详细描述
Description:
This study will be an open-label, randomized, single dose, two-period crossover study to determine the bioavailability of a fixed dose combination capsule formulation of dutasteride and tamsulosin hydrochloride (0.5mg/0.2mg) relative to co-administration of dutasteride 0.5mg capsules and tamsulosin hydrochloride 0.2mg tablets in healthy male subjects of North East Asian and non-Asian ancestry. Subjects will receive single oral doses of a combination capsule formulation of dutasteride 0.5 mg/ tamsulosin 0.2 mg in a fed or fasted state or concomitant dosing of dutasteride 0.5 mg and the Japan-sourced Harnal-D 0.2 mg in a fed or fasted state. Each dose of study medication will be separated by a 28-day washout period. Blood samples for pharmacokinetic analysis will be taken at regular intervals after dosing. Safety will be assessed by measurement of blood pressure, heart rate, safety laboratory data, and review of adverse events. The study will enrol 88 healthy male subjects to ensure that 80 complete the study. At least twenty percent of the study population will be of Japanese ancestry, approximately 20% will be of Chinese ancestry and approximately 20% of Korean ancestry while the remainder of the population will be of non-Asian ancestry.
Background:
Dutasteride (AVODART ™) is an approved potent 5-alpha-reductase inhibitor indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary retention and reduce the risk of the need for BPH-related surgery [AVODART Package Insert, 2009].
In humans, dutasteride is well-tolerated in single doses up to 40mg/day, multiple doses up to 40mg/day administered for 7 days, and 5mg/day administered for 24 weeks. In clinical studies, the overall incidence and type of adverse events (AEs) was similar across the dutasteride, placebo, and finasteride treatment groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Males between 20 and 45 years of age inclusive, at the time of signing the informed consent form.
- •Japanese ancestry defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese, or Korean ancestry defined as being born in Korea, having four ethnic Korean grandparents, holding a Korean passport or identity papers and being able to speak Korean, or Chinese ancestry defined as being born in China, Hong Kong, Singapore or Taiwan, having four ethnic Chinese grandparents, holding a Chinese passport or identity papers and being able to speak Chinese.
- •Japanese, Korean and Chinese subjects should also have lived outside their respective countries for less than 10 years.
- •Male subjects with female partners who are either pregnant or suspected of being pregnant must agree to the use of a condom during sexual activity. This criterion must be followed from the time of the first dose of study medication until 28 days after the last dose of study medication.
- •BMI : For Caucasians: BMI within the range 18 -30 kg/m2 (inclusive); weight range 55-95 kg (inclusive) For East Asians: BMI within the range 18 -28 kg/m2 (inclusive) and height 1.55m-1.85m (inclusive).
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- •Single QTcB < 450 msec.
- •AST, ALT, alkaline phosphatase and bilirubin less than or equal to 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
排除标准
- •Medical Conditions Exclusions:
- •Poor metabolizer for CYP2D6 substrates as determined by genotyping of selected CYP2D6 variants at screening.
- •History of postural hypotension, dizziness, poor hydration, vertigo, vaso-vagal reactions or any other signs and symptoms of orthostasis, which in the opinion of the investigator could be exacerbated by tamsulosin and result in putting the subject at risk of injury.
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- •A positive test for HIV antibody.
- •Subject is mentally or legally incapacitated.
- •Medication Exclusions:
- •Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort, Black Khosh, Dong Quai, Milk Thistle, licorice) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- •History of sensitivity to tamsulosin hydrochloride or durasteride, components thereof or drugs of this class or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- •History of sensitivity to heparin or heparin-induced thrombocytopenia
- •The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- •Lifestyle Exclusions:
- •A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- •History of regular alcohol consumption within 6 months of the screening visit defined by the following Australian guidelines:
- •Males: An average weekly intake greater than 21 units or an average daily intake greater than 3 units. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits and 100 mL of wine.
- •Subjects must be able and willing to abstain from beverages and foods containing alcohol 24 hours prior to and during the dosing day.
- •Consumption of red wine, grapefruit juice, grapefruit and related hybrids, jufen grapes from 7 days prior to the first dose of study medication.
- •Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- •Unwillingness or inability to follow the procedures outlined in the protocol.
研究组 & 干预措施
Fixed dose combination product
Fixed Dose Combination capsule containing dutasteride 0.5mg and tamsulosin 0.2 mg
干预措施: Dutasteride (0.5mg); Tamsulosin hydrochloride (0.2mg); fixed dose combination product of duatsteride (0.5mg) and tamsulosin hydrochloride (0.2mg) (Drug)
结局指标
主要结局
1. To investigate the bioavailability of a combination capsule formulation of dutasteride 0.5 mg/ tamsulosin HCl 0.2 mg relative to concomitant dosing of dutasteride 0.5 mg capsules and tamsulosin 0.2 mg tablets in the fed and fasted states.
时间窗: PK at pre-dose, at 15,30 and 45 min; 1, 2,3,4,6,8,10,12,16,24,48,and 72 hours.
次要结局
- 1. To investigate the effect of food on the bioavailability of a combination capsule formulation of dutasteride 0.5 mg/ tamsulosin HCl 0.2 mg relative to concomitant dosing of dutasteride 0.5 mg capsules and tamsulosin 0.2 mg tablets.(PK at pre-dose, 15, 30,and 45 mins; 1,2,3,4,6,8,10,12,16,24,48,and 72 hrs.)