A Study to Determine the Bioavailability of a Fixed Dose Combination Product of Dutasteride (0.5mg) and Tamsulosin Hydrochloride (0.2mg) Relative to Co-administration of the Individual Components in Healthy Male Subjects of North East Asian and Non-Asian Ancestry. (ARI114694)
|ClinicalTrials.gov Identifier: NCT01254071|
Recruitment Status : Completed
First Posted : December 6, 2010
Last Update Posted : June 12, 2017
|Condition or disease||Intervention/treatment||Phase|
|Prostatic Hyperplasia||Drug: Dutasteride (0.5mg); Tamsulosin hydrochloride (0.2mg); fixed dose combination product of duatsteride (0.5mg) and tamsulosin hydrochloride (0.2mg)||Phase 1|
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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.
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.
Tamsulosin (Harnal, Harnal D, Flomax) is an alpha-1-adrenoceptor blocking agent approved for the treatment of signs and symptoms of benign prostatic hyperplasia. Tamsulosin HCl is extensively metabolized, with less than 10% of the dose excreted in the urine unchanged [Harnal, 2009a; Harnal, 2009b; Flomax, 2009]. In human liver microsomes and human lymphoblastoid cells expressing CYP cDNAs in vitro, tamsulosin HCl is metabolized by both CYP3A4 and CYP2D6 [Matsushima, 1998].
Clinical data exist to support that tamsulosin (an alpha-1-adrenoceptor antagonist), when used in combination with dutasteride (a 5-alpha reductase inhibitor), offers a more effective treatment for the symptoms of benign prostatic hyperplasia than either drug used alone [GSK study ARI40005, GlaxoSmithKline document number HM2002/00171/01]. In addition, data from a large, multi-centre National Institutes of Health-sponsored Medical Therapy of Prostatic Symptoms (MTOPS) study revealed greater benefits of combination alpha-1-adreoceptor antagonist and 5-alpha-reductase inhibitor therapy compared with either monotherapy in males with BPH [McConnell, 2002].
Clinical drug interaction studies have shown no pharmacokinetic or pharmacodynamic interactions between dutasteride and tamsulosin. Dutasteride may be administered with or without food. Tamsulosin should be administered with food. While there is food effect PK data on dutasteride and tamsulosin when administered individually, an objective of this study is to evaluate the effect of food (high fat meal state versus fasted state) on the absorption of dutasteride and tamsulosin HCl when given in a combination capsule formulation relative to the co-administration of the two components, dutasteride and tamsulosin HCl. A previous study, ARI109882, [GlaxoSmithKline document number ZM2007/00022/00], also determined the bioequivalence and food effect of the combination capsule formulation relative to the co-administration of each component administered separately. In that study, the GSK combination capsule was found to be bioequivalent (under both fed and fasted conditions) to the marketed products administered separately. In the present study, the dose of tamsulosin HCl administered will be lower than in ARI109882 (0.2 mg versus 0.4mg administered in ARI109882). The dose of dutasteride is the same in both studies (0.5mg).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||86 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||September 10, 2010|
|Primary Completion Date :||December 21, 2010|
|Study Completion Date :||December 21, 2010|
Experimental: Fixed dose combination product
Fixed Dose Combination capsule containing dutasteride 0.5mg and tamsulosin 0.2 mg
Drug: Dutasteride (0.5mg); Tamsulosin hydrochloride (0.2mg); fixed dose combination product of duatsteride (0.5mg) and tamsulosin hydrochloride (0.2mg)
In the first dosing session, twenty-two subjects of each cohort will receive the FDC capsule (dutasteride and tamsulosin hydrochloride (0.5mg/0.2mg) and the other 22 will receive commercial capsules of dutasteride 0.5mg and commercial tablets of tamsulosin hydrochloride 0.2mg co-administered. Following a wash-out period of at least 28 days, those subjects who received the FDC capsule in session 1, will be co-administered commercial capsules of dutasteride 0.5mg and commercial tablets of tamsulosin hydrochloride 0.2mg while those who were co-administered commercial capsules of dutasteride 0.5mg and commercial tablets of tamsulosin hydrochloride 0.2mg in session 1 will receive the FDC capsule in the second dosing session.
- 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. [ Time Frame: PK at pre-dose, at 15,30 and 45 min; 1, 2,3,4,6,8,10,12,16,24,48,and 72 hours. ]
- 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. [ Time Frame: PK at pre-dose, 15, 30,and 45 mins; 1,2,3,4,6,8,10,12,16,24,48,and 72 hrs. ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01254071
|Australia, New South Wales|
|GSK Investigational Site|
|Randwick, New South Wales, Australia, 2031|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|