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

NCT01495026 | Completed Phase 1

• 1 other identifier: 115708
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostatic Hyperplasia

Keywords

Healthy male subjects; North-East Asian ancestry; Bioequivalence; Food effect; Tamsulosin hydrochloride; Cross-over design; Pilot bioequivalence; Dutasteride (GI198745)

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (3)

• Effect of food on the relative bioavailability of tamsulosin in a selected FDC product in healthy male subjects of North East Asian ancestry

  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

• 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.

  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

• Safety and tolerability of dosing with the different FDC capsule formulations in healthy male subjects of North East Asian ancestry

  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)

Study Arms (3)

Fixed dose combination product

EXPERIMENTAL

Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg

Drug: Dutasteride (0.5mg, fasted state); Drug: Dutasteride (0.5mg, 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)

Dutasteride

EXPERIMENTAL

Commercial formulation of Dutasteride 0.5mg

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)

Harnal-D Tablets

EXPERIMENTAL

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

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)

Interventions

Dutasteride (0.5mg, fasted state) DRUG

Open-label, randomized, single dose, multi-stage, cross-over study

Fixed dose combination product; Harnal-D Tablets

Dutasteride (0.5mg, fed state) DRUG

Commercial formulation of Dutasteride 0.5mg

Fixed dose combination product; Harnal-D Tablets

Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fasted state) DRUG

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)

Dutasteride; Harnal-D Tablets

Fixed dose combination capsule containing dutasteride 0.5mg and tamsulosin 0.2mg (fed state) DRUG

FDC bioequivalent to Harnal-D tablets

Dutasteride; Harnal-D Tablets

Harnal-D Tablets with water (fasted state) DRUG

Commercial formulation of Harnal-D Tablets

Fixed dose combination product

Harnal-D Tablets with water (fed state) DRUG

Commercial formulation of Harnal-D Tablets

Fixed dose combination product

Harnal-D tablets without water (fasted state) DRUG

Commercial formulation of Harnal-D Tablets

Fixed dose combination product

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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%).

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Publications (15)

• AVODART (Dutasteride 0.5 mg) Product Information. March 2011.

  BACKGROUND

• 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.

  PMID: 20160156 BACKGROUND

• FLOMAX (Tamsulosin hydrochloride) Product Information. January, 2011.

  BACKGROUND

• 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.

  BACKGROUND

• 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.

  BACKGROUND

• GlaxoSmithKline Document Number ZM2008/00126/02. Dutasteride Clinical Investigators Brochure v10. Report Date 27 May 2011.

  BACKGROUND

• HARNAL (Tamsulosin hydrochloride 0.2 mg) Product Information. , 2011.

  BACKGROUND

• HARNAL-D (Tamsulosin hydrochloride 0.2 mg) Product Information. , 2009.

  BACKGROUND

• 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.

  PMID: 9492387 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 3450848 BACKGROUND

• GlaxoSmithKline Document Number 2011N112801_00 Study ID ARI114694. GlaxoSmithKline studyARI114694: An open-label, randomized, single dose, two-period cross-over 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.

  RESULT

• GlaxoSmithKline Document Number RM2001/00128/01 Study ID ARI10019. A Double-Blind, Placebo Controlled, Randomized, Parallel Group Study To Investigate The Changes In The Corrected QT Interval Following Repeat Oral Doses Of GI198745 In Healthy Male Volunteers. Report Date 02-Oct-2002.

  RESULT

• GlaxoSmithKline Document Number RM2003/00174/01 Study ID ARI10021. An Open-Label, Single Dose, 2-Way Cross-over Study to Investigate the Pharmacokinetics, Safety and Tolerability of oral Flomax (tamsulosin hydrochloride 0.4mg capsule-US) and Omnic (tamsulosin hydrochloride 0.4mg capsule-Germany) in Healthy Male Volunteers. Report Date 04-Sep-2003.

  RESULT

• GlaxoSmithKline Document Number ZM2007/00022/00 Study ID ARI109882. An Open-Label, Randomized, Single Dose, Three-Period Cross-over 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.

  RESULT

Related Links

• Results for study 115708 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Prostatic Hyperplasia

Interventions

Dutasteride; Tamsulosin

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Azasteroids; Steroids, Heterocyclic; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2011
• First Posted: December 19, 2011
• Study Start: November 6, 2011
• Primary Completion: April 3, 2012
• Study Completion: April 3, 2012
• Last Updated: June 19, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)