This will be an open-label, three-period, fixed-sequence study to evaluate the drug-drug
interaction, pharmacokinetics and safety of dutasteride and tamsulosin when administered
alone and in-combination in Chinese healthy male volunteers.
Inclusion Criteria:
- Ethnic Chinese male subject between the ages of 18 and 45 years old inclusive, at the
time of signing the informed consent.
- Ethnic Chinese are defined as being born in China, having four ethnic Chinese
grandparents, stay in China for most time and be abroad no more than 10 years.
- Healthy subjects defined as individuals who are free from significant
cardiac,pulmonary, gastrointestinal, hepatic, renal, hematological, neurological,
endocrinological and psychiatric disease as determined by medical history,physical
examination, vital signs, electrocardiogram (ECG) and clinical laboratory test
results.
- Body weight >= 50 Kilogram (kg) and BMI within the range 19 - 24 kg/m2(inclusive).
- Serum creatinine < 1. 5xULN at screening.
- Based on single or averaged QTc values of triplicate ECGs obtained over a brief
recording period:
[QTc] < 450 Milliseconds (msec); or QTc < 480 msec in subjects with Bundle Branch Block.
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin ≤ 1. 5xULN
(isolated bilirubin >1. 5xULN is acceptable if bilirubin is fractionated and direct
bilirubin <35%).
- Subjects must be able and willing to stop using of any tobacco or nicotine containing
products 24 hours prior to each dose and for the duration of confinement. At the
discretion of the Investigator, light smokers (smoking ≤10 cigarettes a day) would be
considered for the study inclusion.
- Willing and able of giving written informed consent, which includes compliance with
the all the requirements and restrictions listed in the consent form for the full
duration of the study, and able to understand and follow instructions related to
study procedures.
- Able to swallow and retain oral medication.
- Male subjects with female partners of child-bearing potential must agree to use one
of the contraception methods. This criterion must be followed from the time of the
first dose of study medication until 50 days after the last dose.
Exclusion Criteria:
- The subject has received an investigational product or participated in any other
research trial within 6 months or 5 half-lives, or twice the duration of the
biological effect of any drug (whichever is longer) prior to the first dose of
current study medication or anytime during the study period, or exposure to more than
four new chemical entities within 12 months prior to the first dosing day.
- Previous use of the following medications or involvement in an investigational drug
study of any of these in the previous three months prior to screening:
finasteride, (PROSCAR, PROPECIA) investigational 5 ARIs (i. e., GI198745 and epristeride)
phytotherapy (i. e., over the counter plant extracts for BPH and alopecia) anabolic
steroids (i. e., oxandrolone, testosterone ester) drugs with anti-androgenic properties
(i. e., spironolactone, cimetidine) alpha-1 antagonists (i. e., terazosin, doxazosin,
alfuzosin and tamsulosin) antihypertensive agents or diuretics
- Previous donation of blood or blood products in excess of 500 mL within a 90 day
prior to the first dose of investigational products and the subject agrees not to
donate blood during this study.
- History of regular alcohol consumption within 6 months of the study defined as: an
average weekly intake of >21 units for males. One unit is equivalent to 8 g of
alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure
of spirits. Subjects must be able and willing to abstain from beverages and foods
containing alcohol 24 hours prior to the first dose of study medication and until
collection of the final pharmacokinetic sample during each period.
- Positive test result for Hepatitis B surface antigen (HBsAg), Hepatitis C surface
antibody (HCAb), or HIV antibody at Screening.
- Subjects with a positive urinary drug or alcohol screen at screening and at Day -1of
study participation.
- Poor metabolizer for CYP2D6 substrates as determined by genotyping of selected CYP2D6
variants at screening.
- Subjects with an acute illness requiring treatment by a physician within 30 days
proceeding the screening period of the study, or a significant febrile illness within
five days of the first day the subject will receive the study drug.
- Subjects with sensitivity to currently available 5 ARIs (i. e., finasteride).
- Subjects with sensitivity to currently available alpha 1 antagonists (i. e., terazosin
doxazosin, alfuzosin and tamsulosin). History or presence of allergy, intolerance, or
contraindication to tamsulosin or dutasteride or any of its components, soya or
peanuts, or drugs of these therapeutic classes, or a history of drug or other allergy
(including true sulfonamide allergy) that, in the opinion of the physician
responsible, contraindicates their participation.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- Unable to refrain from the use of prescription or non-prescription drugs, including
vitamins, herbal, dietary supplements within 7 days (or 14 days if the drug is a
potential enzyme inducer, such as St. John's Wort, Black Cohosh, Dong Quai, milk
thistle, and licorice) or 5 half-lives (whichever is longer) prior to the first dose
of study medication and up to 4 days from receiving the last dose of study
medication.
- Unable to refrain from the consumption of red wine, seville oranges, grapefruit or
grapefruit juice and/or pomelos, exotic citrus fruits, grapefruit hybrids or fruit
juices from 7 days prior to the first dose of study medication until collection of
the last blood sample for determination of pharmacokinetic parameters.
- Any clinically significant abnormality on the screening ECG or screening laboratory
tests.
- Current or chronic history of liver disease, or known hepatic or biliary
abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- 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.
- Prior medical history or evidence of prostate cancer (e. g., positive biopsy, or
suspicious ultrasound, or suspicious digital rectal examination (DRE)). Subjects with
suspicious ultrasound or DRE who have had a negative biopsy within the preceding 6
months and stable prostate specific antigen (PSA) are eligible for the study. The
investigator should make every appropriate effort to exclude the possibility of
prostate cancer, including consideration of prostate biopsy in any subject with a
known abnormal PSA.
- History of Breast cancer or clinical breast examination finding suggestive of
malignancy Malignancy within the past five years, except for basal cell carcinoma of
the skin.
Subjects with a prior malignancy who have had no evidence of disease for at least the past
5 years are eligible.
- History of any serious and/or unstable pre-existing medical, psychiatric disorder, or
other conditions that could interfere with a subject's safety, or interfere with the
subject's ability to follow indications or study procedures, or the interpretation of
study results or obtaining informed consent or compliance to study procedures in the
opinion of the Investigator or GSK Medical Monitor.
- History of myocardial infarction, coronary bypass surgery, unstable angina, cardiac
arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident
prior to Screening visit; or diabetes or peptic ulcer disease which is uncontrolled
by medical management.
- Unable to refrain from the use of strong CYP3A4 inhibitors (e. g. ketoconazole) and/or
strong CYP2D6 inhibitors (e. g. paroxetine) throughout the study.
