Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01495026




Registration number
NCT01495026
Ethics application status
Date submitted
15/12/2011
Date registered
19/12/2011
Date last updated
19/06/2018

Titles & IDs
Public title
A Study Assessing a Range of Formulations of the Fixed Dose Combination Product Containing Dutasteride (0.5mg) and Tamsulosin Hydrochloride (0.2mg) to Find a Formulation Which is Bioequivalent to Harnal-D Tablets (Tamsulosin Hydrochloride, 0.2mg) in Healthy Male Subjects From North East Asia
Scientific title
An Open-label, Randomized, Single Dose, Multi-stage, Cross-over Study to Determine the Relative Bioavailability of Fixed Dose Combination Products Containing a 3-oblong Dutasteride Soft Gel Capsule and Tamsulosin (0.5 mg Dutasteride /0.2 mg Tamsulosin HCl) Pellets Having a Range of Tamsulosin Release Rates Produced by Different Mixtures of Enteric Coated and Uncoated Pellets Relative to Harnal-D Tablets, in Healthy Male Subjects of North East Asian Ancestry.
Secondary ID [1] 0 0
115708
Universal Trial Number (UTN)
Trial acronym
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, fasted state)
Treatment: Drugs - Dutasteride (0.5mg, fed state)
Treatment: Drugs - Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
Treatment: Drugs - Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
Treatment: Drugs - Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
Treatment: Drugs - Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fed state)
Treatment: Drugs - Harnal-D Tablets with water (fasted state)
Treatment: Drugs - Harnal-D Tablets with water (fed state)
Treatment: Drugs - Harnal-D tablets without water (fasted state)

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

Experimental: Dutasteride - Commercial formulation of Dutasteride 0.5mg

Experimental: Harnal-D Tablets - Commercial formulation of Harna--D Tablets comprising 0.2mg Tamsulosin Hydrochloride


Treatment: Drugs: Dutasteride (0.5mg, fasted state)
Open-label, randomized, single dose, multi-stage, cross-over study

Treatment: Drugs: Dutasteride (0.5mg, fed state)
Commercial formulation of Dutasteride 0.5mg

Treatment: Drugs: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
FDC with 85%, 65% and 0% of the dose as enteric-coated pellets and with X and/or Y% of the dose as enteric-coated pellets (X and Y to be determined from PK results from Stage 1)

Treatment: Drugs: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
FDC containing faster-release enteric-coated pellets

Treatment: Drugs: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
FDC bioequivalent to Harnal-D tablets

Treatment: Drugs: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fed state)
FDC bioequivalent to Harnal-D tablets

Treatment: Drugs: Harnal-D Tablets with water (fasted state)
Commercial formulation of Harnal-D Tablets

Treatment: Drugs: Harnal-D Tablets with water (fed state)
Commercial formulation of Harnal-D Tablets

Treatment: Drugs: Harnal-D tablets without water (fasted state)
Commercial formulation of Harnal-D Tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Relative bioavailability of tamsulosin from FDC products (0.5 mg dutasteride /0.2 mg tamsulosin HCl) containing a size 3-oblong dutasteride soft gel capsule and tamsulosin pellets having a range of tamsulosin release rates produced by different mixtures
Timepoint [1] 0 0
0, 15 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 48 hr, 72 hr
Secondary outcome [1] 0 0
Effect of food on the relative bioavailability of tamsulosin in a selected FDC product in healthy male subjects of North East Asian ancestry
Timepoint [1] 0 0
0, 15 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 48 hr, 72 hr
Secondary outcome [2] 0 0
Effect of water on the relative bioavailability of tamsulosin in Harnal-D Tablets in the fasted state in healthy male subjects of North East Asian ancestry.
Timepoint [2] 0 0
0, 15 min, 30 min, 45 min, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 16 hr, 24 hr, 48 hr, 72 hr
Secondary outcome [3] 0 0
Safety and tolerability of dosing with the different FDC capsule formulations in healthy male subjects of North East Asian ancestry
Timepoint [3] 0 0
Vital signs: 0, 2 hr, 4 hr, 6 hr, 10 hr, 24 hr, 48 hr and 72 hr. Adverse events: 5 timepoints from pre-dose to follow-up visit (10-14 days post-dose)

Eligibility
Key inclusion criteria
A subject will be eligible for inclusion in this study only if all of the following
criteria apply:

- 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 criterion 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 QTc < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

- 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%).
Minimum age
20 Years
Maximum age
45 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
A subject will not be eligible for inclusion in this study if any of the following criteria
apply:

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.

Medical Exclusions:

- Subjects must be able and willing to refrain from 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 HCl or dutasteride, 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.

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
6/11/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/04/2012
Sample size
Target
Accrual to date
Final
63
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 is an open-label, randomized, single dose, multi-stage, cross-over study in
healthy male subjects of North East Asian ancestry. The aims are to:

- evaluate the pharmacokinetic parameters of several formulations of a fixed dose
combination (FDC) 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 in the fasted state in order to define a formulation which
is bioequivalent to a 0.2 mg orally disintegrating tamsulosin tablet, (Harnal-D Tablets)

- determine the effect of food on the relative bioavailability of tamsulosin in the FDC
product which is assessed to be bioequivalent to Harnal-D Tablets in the fasted state

- assess the effect of water on the relative bioavailability of tamsulosin in Harnal-D
Tablets in the fasted state

- assess the safety and tolerability of dosing with the different FDC capsule formulations
Subjects will receive single oral doses in at least one treatment period; treatment
periods will be 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. Each
stage of the study will enrol 18 subjects to ensure 16 complete. Subjects may consent to
participate in more than one stage.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01495026
Trial related presentations / publications
AVODART (Dutasteride 0.5 mg) Product Information. March 2011.
Cai G, Thiessen JJ, Baidoo CA, Fossler MJ. Operating characteristics of a partial-block randomized crossover bioequivalence study for dutasteride, a drug with a long half-life: investigation through simulation and comparison with final results. J Clin Pharmacol. 2010 Oct;50(10):1142-50. doi: 10.1177/0091270009355155. Epub 2010 Feb 16.
FLOMAX (Tamsulosin hydrochloride) Product Information. January, 2011.
Food and Drug Administration (FDA). Guidance for Industry: Handling and Retention of BA and BE Testing Samples. Centre for Drug Evaluation and Research, USA; 2004.
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 ZM2008/00126/02. Dutasteride Clinical Investigators Brochure v10. Report Date 27 May 2011.
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.
Schuirmann DJ. A comparison of the two one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm. 1987 Dec;15(6):657-80. doi: 10.1007/BF01068419.
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/NCT01495026