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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01495026
First received: December 15, 2011
Last updated: August 30, 2012
Last verified: August 2012
  Purpose

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.

Condition Intervention Phase
Prostatic Hyperplasia
Drug: Dutasteride (0.5mg, fasted state)
Drug: Dutasteride (0.5mg, fed state)
Drug: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
Drug: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fed state)
Drug: Harnal-D Tablets with water (fasted state)
Drug: Harnal-D Tablets with water (fed state)
Drug: Harnal-D tablets without water (fasted state)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Effect of food on the relative bioavailability of tamsulosin in a selected FDC product in healthy male subjects of North East Asian ancestry [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Safety and tolerability of dosing with the different FDC capsule formulations in healthy male subjects of North East Asian ancestry [ Time Frame: 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) ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: November 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fixed dose combination product
Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg
Drug: Dutasteride (0.5mg, fasted state)
Open-label, randomized, single dose, multi-stage, cross-over study
Drug: Dutasteride (0.5mg, fed state)
Commercial formulation of Dutasteride 0.5mg
Drug: Harnal-D Tablets with water (fasted state)
Commercial formulation of Harnal-D Tablets
Drug: Harnal-D Tablets with water (fed state)
Commercial formulation of Harnal-D Tablets
Drug: Harnal-D tablets without water (fasted state)
Commercial formulation of Harnal-D Tablets
Experimental: Dutasteride
Commercial formulation of Dutasteride 0.5mg
Drug: 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)
Drug: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
FDC containing faster-release enteric-coated pellets
Drug: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
FDC bioequivalent to Harnal-D tablets
Drug: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fed state)
FDC bioequivalent to Harnal-D tablets
Experimental: Harnal-D Tablets
Commercial formulation of Harna--D Tablets comprising 0.2mg Tamsulosin Hydrochloride
Drug: Dutasteride (0.5mg, fasted state)
Open-label, randomized, single dose, multi-stage, cross-over study
Drug: Dutasteride (0.5mg, fed state)
Commercial formulation of Dutasteride 0.5mg
Drug: 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)
Drug: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
FDC containing faster-release enteric-coated pellets
Drug: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state)
FDC bioequivalent to Harnal-D tablets
Drug: Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fed state)
FDC bioequivalent to Harnal-D tablets

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   20 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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%).

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01495026

Locations
Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01495026     History of Changes
Other Study ID Numbers: 115708
Study First Received: December 15, 2011
Last Updated: August 30, 2012
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by GlaxoSmithKline:
Healthy male subjects
North-East Asian ancestry
Bioequivalence
Food effect
Tamsulosin hydrochloride
Cross-over design
Pilot bioequivalence
Dutasteride (GI198745)

Additional relevant MeSH terms:
Hyperplasia
Prostatic Hyperplasia
Pathologic Processes
Prostatic Diseases
Genital Diseases, Male
Tamsulosin
Dutasteride
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Urological Agents
Therapeutic Uses
5-alpha Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014