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Bioavailability of Two Combination Products of Dutasteride (0.5mg) and Tamsulosin Hydrochloride (0.2mg) in Asian Males. (ARI115707)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01471678
First Posted: November 16, 2011
Last Update Posted: July 18, 2017
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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
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.

Condition Intervention Phase
Prostatic Hyperplasia Drug: Dutasteride (0.5mg) Drug: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg) Drug: Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl) Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 [ Time Frame: From dosing to 72 hours post-dose ]

Secondary Outcome Measures:
  • 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. [ Time Frame: From dosing to 72 hours post-dose ]
  • 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 [ Time Frame: Vital signs from dosing to 72 hr post-dose. Adverse events monitoring from dosing to 72hr post-dose ]

Enrollment: 27
Actual Study Start Date: June 30, 2011
Study Completion Date: September 7, 2011
Primary Completion Date: September 7, 2011 (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 0.2 mg
Drug: Dutasteride (0.5mg)
This study is an open-label, randomized, single dose, four-period cross-over study.
Drug: 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
Experimental: Dutasteride (0.5mg)
Commercial formulation of dutasteride
Drug: 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);
Experimental: Harnal-D Tablets and Harnal capsules
Commercial formulations of Harnal-D Tablets and Harnal Capsules both comprising 0.2mg tamsulosin HCl
Drug: 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);

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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%).

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01471678


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

Additional Information:
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.
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.

Study Data/Documents: Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 115707
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 115707
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 115707
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 115707
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 115707
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 115707
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 115707
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01471678     History of Changes
Other Study ID Numbers: 115707
First Submitted: October 13, 2011
First Posted: November 16, 2011
Last Update Posted: July 18, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
URL: http://

Keywords provided by GlaxoSmithKline:
Cross-over design
Pilot bioequivalence
North east Asian ancestry
GI198745
Tamsulosin hydrochloride
healthy male subjects
Bioequivalence
Dutasteride

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
Physiological Effects of Drugs
Urological Agents
5-alpha Reductase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists