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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01471678




Registration number
NCT01471678
Ethics application status
Date submitted
13/10/2011
Date registered
16/11/2011
Date last updated
19/06/2018

Titles & IDs
Public title
Bioavailability of Two Combination Products of Dutasteride (0.5mg) and Tamsulosin Hydrochloride (0.2mg) in Asian Males.
Scientific title
An Open-label, Randomized, Single Dose, Four-Period Crossover Study to Compare the Bioavailability of Fixed Dose Combination Capsule Formulations of Dutasteride and Tamsulosin Hydrochloride (0.5 mg/0.2 mg) With 10% and 15% of Enteric Coated Pellets With Harnal-D Tablets and Harnal Capsules Co-administered With Dutasteride (0.5 mg) Soft Gel Capsules in Healthy Male Subjects of North East Asian Ancestry
Secondary ID [1] 0 0
115707
Universal Trial Number (UTN)
Trial acronym
ARI115707
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Hyperplasia 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dutasteride (0.5mg)
Treatment: Drugs - FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg)
Treatment: Drugs - Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl)

Experimental: Fixed dose combination product - Fixed Dose Combination capsule containing dutasteride 0.5mg and tamsulosin 0.2 mg

Experimental: Dutasteride (0.5mg) - Commercial formulation of dutasteride

Experimental: Harnal-D Tablets and Harnal capsules - Commercial formulations of Harnal-D Tablets and Harnal Capsules both comprising 0.2mg tamsulosin HCl


Treatment: Drugs: Dutasteride (0.5mg)
This study is an open-label, randomized, single dose, four-period cross-over study.

Treatment: Drugs: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg)
FDC (with 10% enteric coated tamsulosin pellets); (2): FDC (with 15% enteric coated tamsulosin pellets);

Treatment: Drugs: Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl)
a commercial formulation of dutasteride plus tamsulosin HCl (Harnal-D Tablet); (4): a commercial formulation of dutasteride plus tamsulosin HCl(Harnal Capsule). Each dosing session will be separated by a wash-out period of 5 to 10 days
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Bioavailability of tamsulosin in 2 FDC formulations (Tamsulosin 0.2 mg and Dutasteride 0.5 mg) relative to co-administration of AVODART capsules with Harnal-D tablets or Harnal capsules in male subjects of Asian ancestry in the fed state
Timepoint [1] 0 0
From dosing to 72 hours post-dose
Secondary outcome [1] 0 0
Bioavailability of tamsulosin in one FDC formulation relative to the other FDC formulation (each capsule containing 0.2 mg tamsulosin HCl and 0.5 mg dutasteride) in healthy male subjects of Asian ancestry in the fed state.
Timepoint [1] 0 0
From dosing to 72 hours post-dose
Secondary outcome [2] 0 0
Safety and tolerability of dosing with one FDC formulation relative to the other FDC formulation (each capsule containing 0.2 mg tamsulosin HCl and 0.5 mg dutasteride) in healthy male subjects of Asian ancestry in the fed state
Timepoint [2] 0 0
Vital signs from dosing to 72 hr post-dose. Adverse events monitoring from dosing to 72hr post-dose

Eligibility
Key inclusion criteria
- 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 of child-bearing potential must agree to use one of
the protocol-approved contraception methods .This must be followed from the time of
the first dose of study medication until 45 days after the last dose.

- BMI within the range 18 -28 kg/m2 (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 greater than 1.5xULN is acceptable if bilirubin is fractionated and direct
bilirubin is less than 35%).
Minimum age
20 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Medical Condition 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.

Medical 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.

- A 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 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/09/2011
Sample size
Target
Accrual to date
Final
27
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study aims to determine the relative bioavailability of tamsulosin hydrochloride in a
fixed dose combination capsule of dutasteride and tamsulosin hydrochloride (0.5 mg/0.2 mg)
relative to co-administration of dutasteride 0.5 mg capsules and tamsulosin hydrochloride 0.2
mg tablets or capsules. Two fixed dose combination capsules will be tested; one will contain
tamsulosin hydrochloride pellets with a 15% enteric coating, and the other tamsulosin
hydrochloride pellets with a 10% enteric coat. In addition, two formulations of tamsulosin
hydrochloride will be tested in the co-administration with dutasteride 0.5 mg; a 0.2 mg oral
disintegrating tablet and a 0.2 mg hard shell capsule. This will be an open-label,
randomized, single dose, four-period crossover in healthy male subjects of North East Asian
ancestry. Subjects will receive single oral doses in four treatment periods, each separated
by a 5-10 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 and review of adverse events. The study will enrol approximately 30 healthy male
subjects to ensure that 24 complete the study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01471678
Trial related presentations / publications
AVODART (Dutasteride 0.5 mg) Product Information. February, 2009.
FLOMAX (Tamsulosin hydrochloride) Product Information. January, 2011.
GlaxoSmithKline Document Number 2011N112801_00 Study ID ARI114694. GlaxoSmithKline studyARI114694: 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 (0.5 mg/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;. Report Date 02-May-2011.
GlaxoSmithKline Document Number HM2002/00171/01 Study ID ARI40005. A randomised, double-blind, parallel group study to investigate the efficacy and safety of treatment with Dutasteride (0.5mg) and Tamsulosin (0.4mg), administered once daily for 4 years, alone and in combination, on the improvement of symptoms and clinical outcome in men with moderate to severe symptomatic benign prostatic hyperplasia;. Report Date 09-Jul-2004.
GlaxoSmithKline Document Number ZM2007/00022/00 Study ID ARI109882. An Open-Label, Randomized, Single Dose, Three-Period Crossover Study to Determine the Bioequivalence and Food Effect of a Combination Capsule Formulation of Dutasteride and Tamsulosin Hydrochloride (0.5mg/0.4mg) Compared to Concomitant Dosing of AVODART 0.5mg and FLOMAX 0.4 mg Commercial Capsules in Healthy Male Subjects. Report Date 30-Aug-2007.
HARNAL (Tamsulosin hydrochloride 0.2 mg) Product Information. , 2011.
HARNAL-D (Tamsulosin hydrochloride 0.2 mg) Product Information. , 2009.
Matsushima H, Kamimura H, Soeishi Y, Watanabe T, Higuchi S, Tsunoo M. Pharmacokinetics and plasma protein binding of tamsulosin hydrochloride in rats, dogs, and humans. Drug Metab Dispos. 1998 Mar;26(3):240-5.
McConnell JD. The long term effects of medical therapy on the progression of BPH: Results from the MTOPS Trial (abstract 1042). 167 (4):265, 2002. J. Urology. 2002;167 (4):265.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01471678