Prostatic Hyperplasia
Conditions
Keywords
Bioequivalence, Fasted state, Japanese male healthy subjects, Dutasteride
Brief summary
This will be a single center, open-label, single dose, randomized and 2-way crossover study in healthy Japanese male subjects under fasting conditions. The study will be conducted to determine the bioequivalence between dutasteride capsules manufactured at GSK (test product) and dutasteride capsule manufactured at Catalent (reference product) in healthy Japanese male subjects. Subjects will have a screening visit within 30 days prior to the first dose of study treatment, two treatment periods separated by 28-days washout period, a re-visit 10-14 days after the second dose for the first follow-up and a second follow up via telephone 50-54 days after the second dose. The total duration of the study will be approximately 15 weeks from screening to the second follow up.
Interventions
Dutasteride Capsules are oblong, opaque, dull-yellow, gelatin capsules. The capsules contain 0.5 mg dutasteride for oral administration. The capsules also contain Butylated Hydroxytoluene, Mono-di-glycerides of Caprylic/Capric Acid (MDC), Gelatin, Concentrated Glycerin, Titanium Dioxide, Iron Oxide Yellow as ingredients. This product will be manufactured by GSK, Poznan.
Dutasteride Capsules are oblong, opaque, dull-yellow, gelatin capsules. The capsules contain 0.5 mg dutasteride for oral administration. The capsules also contain Butylated Hydroxytoluene, Mono-di-glycerides of Caprylic/Capric Acid (MDC), Gelatin, Glycerin, Concentrated Glycerin, Titanium Dioxide, Iron Oxide Yellow as ingredients. This product will be manufactured by Catalent, Beinheim.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Between 20 and 64 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the investigator or medically qualified designee 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 Medical Monitor if required agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>=50 kilograms (kg) and body mass index (BMI) within the range 18.5-24.9 kg/meter squared at screening. * Japanese male. * Male subjects with female partners of child bearing potential must comply with the contraception requirements from the time of first dose of study medication until the second follow-up. * Capable of giving signed informed consent as described in which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC 0-t) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Maximal measured plasma concentration (Cmax) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in clinical chemistry parameters | Baseline (screening or Day-1) and Day 2 of each treatment period. | Clinical chemistry parameters includes: blood urea nitrogen, creatinine, uric acid, creatin phosphokinase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase, alkarine phosphatise (ALP), amylase, lactate dehydrogenase, total and direct bilirubin, albumin, fasting glucose, total protein, triglyceride, total cholesterol, high density lipoprotein -cholesterol, low density lipoprotein -cholesterol, potassium, chloride, calcium, phosphorus and sodium. |
| Change from Baseline in routine urinalysis parameters | Baseline (screening or Day-1) and Day 2 of each treatment period. | Routine urinalysis parameters includes: Specific gravity; pH, glucose, protein, blood and ketones, bilirubin and urobilinogen by dipstick; Sediment. |
| Change from Baseline in systolic and diastolic blood pressure measurements | Baseline (screening) and Day 1and Day 2 of each treatment period and at first follow-up visit (approximately up to 11 weeks). | Blood pressure measurements will be collected at screening; pre-dose and 3 hours, 24 hours post-dose in each period; and first follow-up visit. |
| Change from Baseline in pulse rate | Baseline (screening) and Day 1and Day 2 of each treatment period and at first follow-up visit (approximately up to 11 weeks). | Pulse rate measurement will be collected at screening; pre-dose and 3 hours, 24 hours post-dose in each period; and first follow-up visit. |
| Change from Baseline in electrocardiogram (ECG) parameters | Baseline (screening) and Day 1and Day 2 of each treatment period and at first follow-up visit (approximately up to 11 weeks). | Electrocardiograms (ECGs) will be recorded whilst the subject is in a supine position, after 10 minutes of rest. Baseline will be defined as the mean of the three pre-dose measurements (separated by a minimum of 5 minutes) that occurred pre-dose on Day 1. |
| Change from Baseline in body temperature | Baseline (screening) and Day 1and Day 2 of each treatment period and at first follow-up visit (approximately up to 11 weeks). | Body temperature measurement will be collected at screening; pre-dose and 3 hours, 24 hours post-dose in each period; and first follow-up visit. |
| Area under the concentration-time curve from pre-dose to 24 hours (AUC[0-24]) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Area under the plasma concentration-time curve from time zero to infinity (AUC 0-infinity) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Number of subjects with adverse events | Approximately 12 weeks | An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Elimination rate constant (Kel) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Terminal half life (t1/2e) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Percentage of AUC0-infinity obtained by extrapolation (%AUCex) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Apparent clearance following oral dosing (CL/F) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Apparent volume of distribution after oral administration (Vz/F) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Mean residence time (MRT) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Correlation coefficient between time and log concentration of dutasteride for the points used in the estimation of kel. | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Time of the maximum plasma concentration (tmax) of dutasteride test product and reference product | Pre-dose and at the following times post dose: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours) in each period. | Blood samples will be collected for PK analyses in each period before dosing (0 hour) and at the following times after the dose 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 6, 8, 10, 12, 18, 24, 36, 48 and 72 hours. |
| Change from Baseline in hematology parameters | Baseline (screening or Day-1) and Day 2 of each treatment period. | Hematology parameters includes: red blood cells (RBC) count, white blood cell (WBC) count (absolute), platelet count, hemoglobin, hematocrit, RBC indices (mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) |
Countries
Japan
Outcome results
None listed