Prostatic HyperplasiaPhase 1ARI115707NCT01471678
Bioavailability of Two Combination Products of Dutasteride (0.5mg) and Tamsulosin Hydrochloride (0.2mg) in Asian Males.
A Phase 1 study testing Dutasteride (0.5mg), FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg) and Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl) in people with Prostatic Hyperplasia, run by GlaxoSmithKline at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Prostatic Hyperplasia
- What is being tested?
- Dutasteride (0.5mg), FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg) and Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteAustralia
- Study dates
- 30 Jun 2011to 7 Sep 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
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- 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%).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
This study is an open-label, randomized, single dose, four-period crossover study which 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. 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.
BACKGROUND:
Dutasteride (AVODART ™) is an approved potent 5-alpha-reductase inhibitor indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary retention and reduce the risk of the need for BPH-related surgery [AVODART Package Insert, 2009].
In humans, dutasteride is well-tolerated in single doses up to 40mg/day, multiple doses up to 40mg/day administered for 7 days, and 5 mg/day administered for 24 weeks. In single dose clinical studies, the overall incidence and type of adverse events (AEs) was similar across the dutasteride, placebo, and finasteride treatment groups.
Tamsulosin (Harnal, Harnal D, Flomax) is an alpha-1-adrenoceptor blocking agent approved for the treatment of signs and symptoms of benign prostatic hyperplasia. Tamsulosin HCl is extensively metabolized, with less than 10% of the dose excreted in the urine unchanged [Harnal, 2009; Harnal, 2011; Flomax, 2011]. In human liver microsomes and human lymphoblastoid cells expressing CYP cDNAs in vitro, tamsulosin HCl is metabolized by both CYP3A4 and CYP2D6 [Matsushima, 1998].
Clinical data exist to support that tamsulosin (an alpha-1-adrenoceptor antagonist), when used in combination with dutasteride (a 5-alpha reductase inhibitor), offers a more effective treatment for the symptoms of benign prostatic hyperplasia than either drug used alone [GSK study ARI40005, GlaxoSmithKline document number HM2002/00171/01]. In addition, data from a large, multi-centre National Institutes of Health-sponsored Medical Therapy of Prostatic Symptoms (MTOPS) study revealed greater benefits of combination alpha-1-adreoceptor antagonist and 5-alpha-reductase inhibitor therapy compared with either monotherapy in males with BPH [McConnell, 2002].
Clinical drug interaction studies have shown no pharmacokinetic or pharmacodynamic interactions between dutasteride and tamsulosin. Dutasteride may be administered with or without food. Tamsulosin should be administered with food. Food effect PK data exists for co-administration of dutasteride and tamsulosin given in a fixed dose combination (FDC) capsule formulation relative to the co-administration of the two components, dutasteride and tamsulosin HCl; GSK studies ARI109882, [GlaxoSmithKline document number ZM2007/00022/00], and ARI114694, [GlaxoSmithKline document number ZM2010/00028/00]. In the latter study, the dose of tamsulosin HCl administered was 0.2 mg versus 0.4mg administered in ARI109882. The dose of dutasteride was the same in both studies (0.5mg). In ARI109882, the GSK combination capsule was found to be bioequivalent (under both fed and fasted conditions) to the marketed products administered separately. ARI114694 demonstrated bioequivalence for dutasteride but not for tamsulosin when administered as an FDC product (of dutasteride 0.5 mg and tamsulosin 0.2 mg) relative to co-administration of separate commercial formulations of dutasteride (0.5 mg) and tamsulosin (0.2 mg) in the fed and fasted stage in different North East Asian ethnic groups.
This study aims to investigate the bioequivalence of tamsulosin only by investigating two different FDC formulations with 10 % or 15% Enteric Coated Tamsulosin pellets (0.2 mg) and Dutasteride 0.5 mg relative to co-administration of a commercial formulation of dutasteride (0.5 mg) and two different commercial formulations of 0.2 mg tamsulosin,Harnal Capsule and Harnal-D Tablet. Specifically, the study aims to investigate the bioavailability of the following:
- FDC (with 10% enteric coated tamsulosin pellets) to a commercial formulation of dutasteride plus tamsulosin (Harnal-D Tablet)
- FDC (with 10% enteric coated tamsulosin pellets) to a commercial formulation of dutasteride plus tamsulosin (Harnal Capsule)
- FDC (with 15% enteric coated tamsulosin pellets) to a commercial formulation of dutasteride plus tamsulosin (Harnal-D Tablet) (also investigated in ARI114694)
- FDC (with 15% enteric coated tamsulosin pellets) to a commercial formulation of dutasteride plus tamsulosin (Harnal Capsule) Both Harnal-D tablets and Harnal capsules are included as comparators as bioequivalence of the 10 or 15 % FDC formulations to Harnal Capsules would provide a registration pathway for China, where Harnal Capsules are commercially available. As Harnal capsules are not available in Korea and Japan, bioequivalence to Harnal-D tablets would allow the FDC to be registered in China, Korea and Japan, where Harnal-D tablets are approved.
- Conditions
- Prostatic Hyperplasia
- Being tested
- Dutasteride (0.5mg), FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg), Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl)
- Keywords
- Cross-over design, Pilot bioequivalence, North east Asian ancestry, GI198745, Tamsulosin hydrochloride, healthy male subjects, Bioequivalence, Dutasteride
- Medical subject headings
- Prostatic Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dutasteride (0.5mg)Drug
This study is an open-label, randomized, single dose, four-period cross-over study.
FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg)Drug
FDC (with 10% enteric coated tamsulosin pellets); (2): FDC (with 15% enteric coated tamsulosin pellets);
Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl)Drug
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
| Study group | Role | What they receive |
|---|---|---|
| Fixed dose combination product | Experimental | Fixed Dose Combination capsule containing dutasteride 0.5mg and tamsulosin 0.2 mg Receives: Drug: Dutasteride (0.5mg); Drug: Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl) |
| Dutasteride (0.5mg) | Experimental | Commercial formulation of dutasteride Receives: Drug: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg) |
| Harnal-D Tablets and Harnal capsules | Experimental | Commercial formulations of Harnal-D Tablets and Harnal Capsules both comprising 0.2mg tamsulosin HCl Receives: Drug: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: From dosing to 72 hours post-dose
Secondary outcomes (2)
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.
Measured: 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
Measured: Vital signs from dosing to 72 hr post-dose. Adverse events monitoring from dosing to 72hr post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2011 (estimated)
- Study start30 Jun 2011
- Primary completion7 Sep 2011
- Study completion7 Sep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Prostatic HyperplasiaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01471678
- Sponsor's protocol ID
- 115707
- Acronym
- ARI115707
- Status last verified
- Jun 2018
- First submitted
- 13 Oct 2011
- Last updated
- 19 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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.
PubMed 9492387McConnell 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 at a glance
From the registry record, last updated by the sponsor on 19 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01471678
- Acronym / sponsor ID
- ARI115707 / 115707
- Conditions
- Prostatic Hyperplasia
- Keywords
- Cross-over design, Pilot bioequivalence, North east Asian ancestry, GI198745, Tamsulosin hydrochloride, healthy male subjects, Bioequivalence, Dutasteride
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 30 Jun 2011 (actual)
- Primary completion
- 7 Sep 2011 (actual)
- Study completion
- 7 Sep 2011 (actual)
- First posted
- 16 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is an open-label, randomized, single dose, four-period crossover study which 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. 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.
BACKGROUND:
Dutasteride (AVODART ™) is an approved potent 5-alpha-reductase inhibitor indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary retention and reduce the risk of the need for BPH-related surgery [AVODART Package Insert, 2009].
In humans, dutasteride is well-tolerated in single doses up to 40mg/day, multiple doses up to 40mg/day administered for 7 days, and 5 mg/day administered for 24 weeks. In single dose clinical studies, the overall incidence and type of adverse events (AEs) was similar across the dutasteride, placebo, and finasteride treatment groups.
Tamsulosin (Harnal, Harnal D, Flomax) is an alpha-1-adrenoceptor blocking agent approved for the treatment of signs and symptoms of benign prostatic hyperplasia. Tamsulosin HCl is extensively metabolized, with less than 10% of the dose excreted in the urine unchanged [Harnal, 2009; Harnal, 2011; Flomax, 2011]. In human liver microsomes and human lymphoblastoid cells expressing CYP cDNAs in vitro, tamsulosin HCl is metabolized by both CYP3A4 and CYP2D6 [Matsushima, 1998].
Clinical data exist to support that tamsulosin (an alpha-1-adrenoceptor antagonist), when used in combination with dutasteride (a 5-alpha reductase inhibitor), offers a more effective treatment for the symptoms of benign prostatic hyperplasia than either drug used alone [GSK study ARI40005, GlaxoSmithKline document number HM2002/00171/01]. In addition, data from a large, multi-centre National Institutes of Health-sponsored Medical Therapy of Prostatic Symptoms (MTOPS) study revealed greater benefits of combination alpha-1-adreoceptor antagonist and 5-alpha-reductase inhibitor therapy compared with either monotherapy in males with BPH [McConnell, 2002].
Clinical drug interaction studies have shown no pharmacokinetic or pharmacodynamic interactions between dutasteride and tamsulosin. Dutasteride may be administered with or without food. Tamsulosin should be administered with food. Food effect PK data exists for co-administration of dutasteride and tamsulosin given in a fixed dose combination (FDC) capsule formulation relative to the co-administration of the two components, dutasteride and tamsulosin HCl; GSK studies ARI109882, [GlaxoSmithKline document number ZM2007/00022/00], and ARI114694, [GlaxoSmithKline document number ZM2010/00028/00]. In the latter study, the dose of tamsulosin HCl administered was 0.2 mg versus 0.4mg administered in ARI109882. The dose of dutasteride was the same in both studies (0.5mg). In ARI109882, the GSK combination capsule was found to be bioequivalent (under both fed and fasted conditions) to the marketed products administered separately. ARI114694 demonstrated bioequivalence for dutasteride but not for tamsulosin when administered as an FDC product (of dutasteride 0.5 mg and tamsulosin 0.2 mg) relative to co-administration of separate commercial formulations of dutasteride (0.5 mg) and tamsulosin (0.2 mg) in the fed and fasted stage in different North East Asian ethnic groups.
This study aims to investigate the bioequivalence of tamsulosin only by investigating two different FDC formulations with 10 % or 15% Enteric Coated Tamsulosin pellets (0.2 mg) and Dutasteride 0.5 mg relative to co-administration of a commercial formulation of dutasteride (0.5 mg) and two different commercial formulations of 0.2 mg tamsulosin,Harnal Capsule and Harnal-D Tablet. Specifically, the study aims to investigate the bioavailability of the following:
- FDC (with 10% enteric coated tamsulosin pellets) to a commercial formulation of dutasteride plus tamsulosin (Harnal-D Tablet)
- FDC (with 10% enteric coated tamsulosin pellets) to a commercial formulation of dutasteride plus tamsulosin (Harnal Capsule)
- FDC (with 15% enteric coated tamsulosin pellets) to a commercial formulation of dutasteride plus tamsulosin (Harnal-D Tablet) (also investigated in ARI114694)
- FDC (with 15% enteric coated tamsulosin pellets) to a commercial formulation of dutasteride plus tamsulosin (Harnal Capsule) Both Harnal-D tablets and Harnal capsules are included as comparators as bioequivalence of the 10 or 15 % FDC formulations to Harnal Capsules would provide a registration pathway for China, where Harnal Capsules are commercially available. As Harnal capsules are not available in Korea and Japan, bioequivalence to Harnal-D tablets would allow the FDC to be registered in China, Korea and Japan, where Harnal-D tablets are approved.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fixed dose combination product | Experimental | Drug: Dutasteride (0.5mg), Drug: Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl)Fixed Dose Combination capsule containing dutasteride 0.5mg and tamsulosin 0.2 mg |
| Dutasteride (0.5mg) | Experimental | Drug: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg)Commercial formulation of dutasteride |
| Harnal-D Tablets and Harnal capsules | Experimental | Drug: FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg)Commercial formulations of Harnal-D Tablets and Harnal Capsules both comprising 0.2mg tamsulosin HCl |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dutasteride (0.5mg)This study is an open-label, randomized, single dose, four-period cross-over study. | Drug | Fixed dose combination product |
| 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); | Drug | Dutasteride (0.5mg), Harnal-D Tablets and Harnal capsules |
| 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 | Drug | Fixed dose combination product |
Primary outcome
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
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2018.
- BackgroundAVODART (Dutasteride 0.5 mg) Product Information. February, 2009.
- BackgroundFLOMAX (Tamsulosin hydrochloride) Product Information. January, 2011.
- BackgroundGlaxoSmithKline 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.
- BackgroundGlaxoSmithKline 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.
- BackgroundGlaxoSmithKline 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.
- BackgroundHARNAL (Tamsulosin hydrochloride 0.2 mg) Product Information. , 2011.
- BackgroundHARNAL-D (Tamsulosin hydrochloride 0.2 mg) Product Information. , 2009.
- Background: PubMed 9492387Matsushima 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.
- BackgroundMcConnell 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.
- Results for study 115707 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dutasteride (0.5mg), FDC product of dutasteride (0.5mg) and tamsulosin HCl (0.2mg) and Harnal D Tablets and Harnal Capsules (both comprising 0.2 mg tamsulosin HCl) in people with Prostatic Hyperplasia, run by GlaxoSmithKline at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01471678, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2018.