Last updated: 11/07/2018 11:20:58
Comparative Bioavailability of Two Fixed Dose Combination (FDC) Formulations of Dutasteride and Tamsulosin Hydrochloride relative to Co-administration of Dutasteride with Tamsulosin Hydrochloride in Healthy Male Subjects under Fed and Fasted states
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: An Open-label, Randomized, Single Dose, three-way Crossover study to determine the Bioavailability of Two Fixed Dose Combination Capsule Formulations of Dutasteride and Tamsulosin Hydrochloride (0.5mg/0.2mg) Relative to Co-administration of Dutasteride 0.5mg capsules and Tamsulosin Hydrochloride 0.2mg tablets in Healthy Male Subjects in the fed and fasted states
Trial description: 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.
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Area under the curve from 0 to the time of the last quantifiable concentration (AUC[0-t]) of tamsulosin in serum
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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.
Secondary outcomes:
Time to reach maximum serum concentration (tmax) of tamsulosin and dutasteride in serum
Timeframe: 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).
Timeframe: 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])
Timeframe: Up to Day 110
Safety and tolerability as assessed by electrocardiogram (ECG) measurements
Timeframe: Up to Day 110
Safety and tolerability as assessed by review of adverse events (AEs)
Timeframe: Up to Day 110
Safety and tolerability as assessed by clinical laboratory safety data
Timeframe: Up to Day 56
Interventions:
Enrollment:
84
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Olivia Burns, John Zhu, Michael J Manyak, Ramiya Ravindranath, Fariba Koosha, Nazneen Haque, Sally Chung. Relative bioavailability of fixed-dose combinations of tamsulosin and dutasteride: results from two randomized trials in healthy male volunteers. Clin Pharmacol Drug Devel. 2017
Medical condition
Prostatic Hyperplasia
Product
dutasteride, dutasteride/tamsulosin, tamsulosin
Collaborators
Not applicable
Study date(s)
July 2014 to February 2015
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
- 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.
- Criteria Based Upon Medical Histories
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Inclusion and exclusion criteria
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)
Exclusion criteria:
- Criteria Based Upon Medical Histories
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.
- 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 regular alcohol consumption within 6 months of the study defined for US sites as: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 millilitre [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- History of diabetes or peptic ulcer disease which is uncontrolled by medical management.
- History of breast cancer or clinical breast examination finding suggestive of malignancy. History of malignancy within the past five 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 (e.g., positive biopsy, or suspicious ultrasound, or suspicious digital rectal examination [DRE]). Patients with suspicious ultrasound or DRE who have had a negative biopsy within the preceding 6 months and stable prostate specific antigen (PSA) are eligible for the study. Note: The investigator should make every appropriate effort to exclude the possibility of prostate cancer, including consideration of prostate biopsy in any subject with a known abnormal PSA. Criteria Based Upon Diagnostic Assessments
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening;
- A positive pre-study drug/alcohol screen.
- A positive test for Human Immunodeficiency Virus (HIV) antibody. Other Criteria
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
Trial location(s)
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21225
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
Not applicable
Actual study completion date
2015-23-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 117057 can be found on the GSK Clinical Study Register.
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