Prostatic Hyperplasia
Conditions
Keywords
bioavailability, crossover design, healthy male volunteers, tamsulosin hydrochloride, Dutasteride
Brief summary
This study will be an open-label, randomized, single dose, three way crossover study in healthy male subjects. The aim of the study is to evaluate the pharmacokinetic parameters of two formulations of a fixed dose combination (FDC) capsule of dutasteride and tamsulosin hydrochloride (HCl) (0.5 milligram \[mg\]/0.2 mg) relative to co-administration of dutasteride 0.5 mg capsules and tamsulosin hydrochloride 0.2 mg tablets in both the fed and fasted states. Approximately 84 healthy adult male subjects will be enrolled into the study and split into two cohorts (fed and fasted), allowing for approximately 36 subjects to complete each cohort. Subjects from both cohorts will receive single oral doses in 3 treatment periods and be randomized to one of six different treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA) wherein A= FDC1: Dutasteride and tamsulosin HCl (0.5 mg/0.2 mg), B= FDC2: Dutasteride and tamsulosin HCl (0.5 mg/0.2 mg), C= Co-administration of commercial formulations of dutasteride(0.5mg) and tamsulosin HCl (0.2mg). Each treatment period will be separated by a minimum 28 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.
Interventions
FDC 1 - Fixed dose combination capsule of dutasteride and tamsulosin hydrochloride (0.5 mg/0.2 mg). Each capsule will contain dutasteride (0.5 mg) (CJ) and tamsulosin pellets (0.2 mg) version 1.
FDC 2 - Fixed dose combination capsule of dutasteride and tamsulosin hydrochloride (0.5 mg/0.2 mg). Each capsule will contain dutasteride (0.5 mg) (CL) and tamsulosin pellets (0.2 mg) version 2.
Co-administration of dutasteride 0.5 mg capsule (Oblong, size 6, dull yellow capsules: Commercially available) and tamsulosin hydrochloride 0.2 mg tablet (White, round standard convex tablet: Commercially available).
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Males aged between 18 and 65 years of age inclusive, at the time of signing the informed consent. * 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 parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the Investigator, in consultation with the GSK Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 18 - 32 kg/m\^2 (square meter) (inclusive). * Male subjects with female partners of child-bearing potential must agree to use a condom. This criterion must be followed from the time of the first dose of study medication until 50 days post-last dose. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Able to swallow and retain oral medication. * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) \<2x (Upper limit of normal) ULN; alkaline phosphatase and bilirubin \<=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Based on single or averaged corrected QT (QTc) values of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QT duration corrected for heart rate by Fridericia's formula (QTcF) \<450 milliseconds (msec)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve from 0 to the time of the last quantifiable concentration (AUC[0-t]) of tamsulosin in serum | Pre-dose and post dose at 15 minutes (min), 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours (h). | Relative bioavailability of tamsulosin will be assessed by evaluating AUC (0-t). |
| Area under the curve from 0 to infinity (AUC[0-infinity]) of tamsulosin in serum | Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose. | Relative bioavailability of tamsulosin will be assessed by evaluating AUC (0-infinity). |
| Maximum drug concentration (Cmax) of dutasteride in serum | Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose. | Relative bioavailability of dutasteride will be assessed by evaluating Cmax |
| AUC(0-t) of dutasteride in serum | Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose. | Relative bioavailability of dutasteride will be assessed by evaluating AUC(0-t) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability as assessed by review of adverse events (AEs) | Up to Day 110 | AEs will be collected from the start of dosing with Investigational Product and until the follow-up visit |
| Time to reach maximum serum concentration (tmax) of tamsulosin and dutasteride in serum | Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose | Pharmacokinetics of dutasteride and tamsulosin will be characterised by measuring tmax. |
| Safety and tolerability as assessed by clinical laboratory safety data | Up to Day 56 | Clinical laboratory tests will include hematology, clinical chemistry and urinalysis |
| Terminal half-life (t½) of tamsulosin in serum (as data permit). | Pre-dose and post dose at 15 min, 30 min, 45 min, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 h post dose | Pharmacokinetics of dutasteride and tamsulosin will be characterised by measuring t½ |
| Safety and tolerability as assessed by Vital signs (blood pressure and pulse rate [PR]) | Up to Day 110 | Vital sign measurements will be measured in supine position after 5 minutes rest and will include systolic and diastolic blood pressure and pulse rate. Baseline for vital signs will be defined as the mean of the two blood pressure and pulse readings on Day -1. |
| Safety and tolerability as assessed by electrocardiogram (ECG) measurements | Up to Day 110 | Single 12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Baseline for ECG will be defined as the mean of three measurements on Day -1 |
Countries
United States
Outcome results
None listed