An Open Label, Single Sequence, Three Period, Drug-Drug Interaction Study To Examine The Pharmacokinetics Of Dutasteride And Tamsulosin And Their Interactions In Chinese Male Healthy Volunteers
Overview
- Phase
- Phase 1
- Intervention
- Dutasteride and Tamsulosin
- Conditions
- Prostatic Hyperplasia
- Sponsor
- GlaxoSmithKline
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- To evaluate the pharmacokinetics of dutasteride and tamsulosin when dosed alone and in combination
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Detailed Description
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. The study will last approximately eleven weeks. Blood samples for pharmacokinetic analysis will be taken at pre-specified times. Safety will be assessed by measurement of concurrent medication,changes in clinical laboratory values, ECG, vital signs, and collection of adverse events.Approximately 24 healthy adult males will be enrolled such that approximately 18 subjects complete dosing and critical assessments.This will be an open label, single sequence, three-period study. Approximately 24 healthy male volunteers will be enrolled. At the first study period, the subjects will receive 0.5mg of dutasteride (Dut) as a single dose (SD) under fed conditions. Serum sampling will take place pre-dose and over the next 72 hours post dose (Per. A). After a 28-30 days washout, the subjects will be brought in and be given 0.2mg tamsulosin as Harnal D tablet for 7 days with the morning meal. Serum sampling for pharmacokinetics of tamsulosin will take place at day 1, day 2 and day 3 pre-dose and at days 4 for 24 hours (Per. B). On the next day (Day 5), the subjects will be given both 0.2mg tamsulosin Harnal D tablet and 0.5mg of dutasteride. Serum sampling will take place at Day 5 pre-dose and followed for 72 hours (Per. C) for both dutasteride and tamsulosin. Subjects will participate in a follow-up visit approximately 2 weeks after the last dose of study drug.
Investigators
Eligibility Criteria
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.
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).
Arms & Interventions
Dutasteride with/ without Tamsulosin
All subjects will be assigned to the same treatment group
Intervention: Dutasteride and Tamsulosin
Outcomes
Primary Outcomes
To evaluate the pharmacokinetics of dutasteride and tamsulosin when dosed alone and in combination
Time Frame: Pre-dose (within 10 minutes of the dutasteride administration), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose.Pre-dose (within 10 minutes of tamsulosin administration) on Day 1, Day 2 and Day 3 and pre-dose, 0.25, 0.5, 1, 2, 3, 4, 6,
Serum dutasteride AUC (0-t), Cmax, tmax, following 0.5mg single dose administration with and without tamsulosin 0.2mg q24h. Serum tamsulosin AUC(0-τ), Cmax, tmax, Cτ and CL/F following 0.2mg q24h administration with and without dutasteride 0.5mg single dose.
Secondary Outcomes
- To evaluate the safety and tolerability of dutasteride and tamsulosin when administered alone and in combination.(11 Weeks)