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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Fasted state | Experimental | Treatment will be administered orally to 42 subjects in the fasted state. Subjects will be required to fast overnight (minimum 10 hours) and for a minimum of 4 hours after each dose. Subjects will participate in 3 treatment periods and assigned to one of six treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA) in accordance with the randomization schedule generated by Clinical Statistics. The three treatment periods will be separated by a minimum washout period of 28 days |
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| Cohort 2 : Fed state | Experimental | Treatment will be administered orally to 42 subjects in the fed state (high fat breakfast). Dosing will take place within 30 minutes of the start of the meal. Subjects will participate in 3 treatment periods and assigned to one of six treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA) in accordance with the randomization schedule generated by Clinical Statistics. The three treatment periods will be separated by a minimum washout period of 28 days |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treatment sequence A | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the curve from 0 to the time of the last quantifiable concentration (AUC[0-t]) of tamsulosin in serum | Relative bioavailability of tamsulosin will be assessed by evaluating AUC (0-t). | 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). |
| Area under the curve from 0 to infinity (AUC[0-infinity]) of tamsulosin in serum | Relative bioavailability of tamsulosin will be assessed by evaluating AUC (0-infinity). | 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. |
| Maximum drug concentration (Cmax) of dutasteride in serum | Relative bioavailability of dutasteride will be assessed by evaluating Cmax | 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. |
| AUC(0-t) of dutasteride in serum | Relative bioavailability of dutasteride will be assessed by evaluating AUC(0-t) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to reach maximum serum concentration (tmax) of tamsulosin and dutasteride in serum | Pharmacokinetics of dutasteride and tamsulosin will be characterised by measuring tmax. | 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 |
| Terminal half-life (t½) of tamsulosin in serum (as data permit). |
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Inclusion Criteria:
Exclusion Criteria:
Criteria Based Upon Medical Histories
Criteria Based Upon Diagnostic Assessments
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Baltimore | Maryland | 21225 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28800206 | Derived | Burns O, Zhu J, Manyak MJ, Ravindranath R, Koosha F, Haque N, Chung S. Relative Bioavailability of Fixed-Dose Combinations of Tamsulosin and Dutasteride: Results From 2 Randomized Trials in Healthy Male Volunteers. Clin Pharmacol Drug Dev. 2018 May;7(4):422-434. doi: 10.1002/cpdd.380. Epub 2017 Aug 11. |
| Label | URL |
|---|---|
| Results for study 117057 can be found on the GSK Clinical Study Register. | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| 117057 | Annotated Case Report Form | View IPD |
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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| Treatment sequence B | Drug | 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. |
|
| Treatment sequence C | Drug | 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). |
|
Pharmacokinetics of dutasteride and tamsulosin will be characterised by measuring t½ |
| 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 |
| Safety and tolerability as assessed by Vital signs (blood pressure and pulse rate [PR]) | 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. | Up to Day 110 |
| Safety and tolerability as assessed by electrocardiogram (ECG) measurements | 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 | Up to Day 110 |
| Safety and tolerability as assessed by review of adverse events (AEs) | AEs will be collected from the start of dosing with Investigational Product and until the follow-up visit | Up to Day 110 |
| Safety and tolerability as assessed by clinical laboratory safety data | Clinical laboratory tests will include hematology, clinical chemistry and urinalysis | Up to Day 56 |
For additional information about this study please refer to the GSK Clinical Study Register |
| 117057 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117057 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117057 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117057 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117057 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| 117057 | Statistical Analysis Plan | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| ID | Term |
|---|---|
| D011470 | Prostatic Hyperplasia |
| ID | Term |
|---|---|
| D011469 | Prostatic Diseases |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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