Overview

Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin Hydrochloride (HCL) Combination Capsule in Fasted State

Status:
Completed
Trial end date:
2014-12-29
Target enrollment:
0
Participant gender:
Male
Summary
The purpose of this study is to assess the bioequivalence of the second generation dutasteride and tamsulosin hydrochloride (HCL) combination capsule versus currently available commercial combination of dutasteride 0.5 milligram (mg) and tamsulosin HCL 0.4 mg capsule in healthy adult male subjects. Subjects in this study will receive either a single oral dose of the second generation dutasteride 0.5 mg and tamsulosin 0.4 mg combination capsule or a single dose of commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg followed by a 28-day washout period both in fasted state. The study will enroll approximately 92 healthy adult male subjects in order to complete approximately 76 evaluable subjects. The total duration of a subject's involvement in this study is anticipated to be approximately 12 weeks.
Phase:
Phase 1
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
GlaxoSmithKline
Treatments:
Dutasteride
Tamsulosin
Criteria
Inclusion Criteria:

- Males who are 18 to 50 years of age, inclusive.

- Weight range 55 to 95 kg (inclusive) and body mass index (BMI) 18 to 30
kilogram/meter^2 (kg/m^2) (inclusive).

- Healthy subjects defined as individuals who are free from clinically significant
illness or disease as determined by the investigator based on their medical history,
physical examination, vital signs, laboratory studies, and electrocardiograms (ECGs).

- Single QT interval corrected (QTc) <450 millisecond (msec) or QTc <480 msec in
subjects with Bundle Branch Block, no clinically relevant abnormal finding on the
screening ECG.

- Serum creatinine <1.5 x upper limit of normal (ULN) at screening.

- Cytochrome P450 enzyme 2D6 (CYP2D6) Extensive Metabolizers only at screening

- Willing and able to give written informed consent.

- Able to swallow and retain oral medication.

- Male subjects with female partners of child-bearing potential must agree to use 1 of
the contraception methods. - Aspartate aminotransferase (AST), alanine
aminotransferase (ALT), alkaline phosphatise (ALP), and bilirubin <=1.5 x ULN
(isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct
bilirubin <35%).

Exclusion Criteria:

- 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.

- 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 GlaxoSmithKline (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.

- History of breast cancer or clinical breast examination finding suggestive of
malignancy, malignancy within the past 5 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.

- Prior medical history or evidence of prostate cancer. Subjects with suspicious
ultrasound or Digital Rectal Examination (DRE) who have had a negative biopsy within
the preceding 6 months and stable prostate specific antigen (PSA) are eligible for the
study.

- 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.

- Positive human immunodeficiency virus (HIV) test at screening.

- Use of prescription or non-prescription drugs.

- Strong Cytochrome P450 enzyme 3A4 (CYP3A4) inhibitors (e.g. ketoconazole) and/or
strong CYP2D6 inhibitors (e.g. paroxetine) usage throughout the study.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- History of regular alcohol consumption exceeding 21 drinks/week for men (1 unit is
equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 millilitre [mL]) of
beer, 1 glass (equivalent to 125 mL) of wine or 1 (equivalent to 25 mL) measure of
spirits) within 6 months of screening. 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 the completion of the final PK sample during each period.

- A positive urine drug or alcohol screen result at screening and at Day -1. A minimum
list of drugs that will be screened for include amphetamines, barbiturates, cocaine,
opiates, cannabinoids, and benzodiazepines.

- 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.

- 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, exposure to more than 4 new
chemical entities within 12 months prior to the first dosing day.

- 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 or presence of allergy, intolerance, contraindication or sensitivity to alpha
blockers (e.g., tamsulosin), or 5 alpha reductase inhibitors (e.g., dutasteride) or
drugs of these therapeutic classes, soya or peanuts, or any ingredients of Combodart,
or a history of drug or other allergy (including true sulfonamide allergy) that, in
the opinion of the investigator, contraindicates your participation in the study.