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Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin HCl Combination Capsule in Fed State

Primary Purpose

Urologic Diseases

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg
Second generation dutasteride 0.5 mg and tamsulosin HCL 0.4 mg combination capsule
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Urologic Diseases focused on measuring combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg, Tamsulosin, healthy subject, bioequivalence, GI198745, dutasteride, tamsulosin hydrochloride

Eligibility Criteria

18 Years - 50 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Males who are 18 to 50 years of age, inclusive.
  • Weight range 55 to 95 kg (inclusive) and body mass index (BMI) 18 to 30 kilogram/meter^2 (kg/m^2) (inclusive).
  • Healthy subjects defined as individuals who are free from clinically significant illness or disease as determined by the investigator based on their medical history, physical examination, vital signs, laboratory studies, and electrocardiograms (ECGs).
  • Single QTc <450 millisecond (msec) or QTc <480 msec in subjects with Bundle Branch Block, no clinically relevant abnormal finding on the screening ECG.
  • Serum creatinine <1.5 x upper limit of normal (ULN) at screening.
  • CYP2D6 Extensive Metabolizers only at screening
  • Willing and able to give written informed consent
  • Able to swallow and retain oral medication.
  • Male subjects with female partners of child-bearing potential must agree to use 1 of the contraception methods.
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), and bilirubin <=1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

Exclusion Criteria:

  • 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 any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with a subject's safety, or interfere with the subject's ability to follow indications or study procedures, or the interpretation of study results or obtaining informed consent or compliance to study procedures in the opinion of the Investigator or GSK Medical Monitor.
  • History of myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident prior to Screening visit; or diabetes or peptic ulcer disease which is uncontrolled by medical management.
  • History of breast cancer or clinical breast examination finding suggestive of malignancy, malignancy within the past 5 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. Subjects 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.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • Positive human immunodeficiency virus (HIV) test at screening.
  • Use of prescription or non-prescription drugs.
  • Strong CYP3A4 inhibitors (e.g. ketoconazole) and/or strong CYP2D6 inhibitors (e.g. paroxetine) usage throughout the study.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • History of regular alcohol consumption exceeding 21 drinks/week for men (1 unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 millilitre [mL]) of beer, 1 glass (equivalent to 125 mL) of wine or 1 (equivalent to 25 mL) measure of spirits) within 6 months of screening. 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 the completion of the final PK sample during each period.
  • A positive urine drug or alcohol screen result at screening and at Day -1. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines.
  • 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.
  • 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, exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • 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 or presence of allergy, intolerance, contraindication or sensitivity to alpha blockers (e.g., tamsulosin), or 5 alpha reductase inhibitors (e.g., dutasteride) or drugs of these therapeutic classes, soya or peanuts, or any ingredients of commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg, or a history of drug or other allergy (including true sulfonamide allergy) that, in the opinion of the investigator, contraindicates your participation in the study.

Sites / Locations

  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Sequence AB

Sequence BA

Arm Description

Subjects will receive Treatment A (commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg) in period 1 and Treatment B (combination of second generation dutasteride 0.5 mg and tamsulosin HCL 0.4 mg combination) in period 2 orally once daily under fed condition.

Subjects will be randomized to receive Treatment B (combination of second generation dutasteride 0.5 mg and tamsulosin HCl 0.4 mg combination) in period 1 and Treatment A (commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg) in period 2 orally once daily under fed condition.

Outcomes

Primary Outcome Measures

Pharmacokinetic profile for second generation dutasteride when co-administered with tamsulosin HCL relative to the currently available commercial combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg in the fed state to investigate bioequivalence
PK parameters include: area under the concentration-time curve from time zero to last time of quantifiable concentration within a subject (AUC [0-t]), and maximum observed concentration (Cmax) as data permit.
Composite of PK parameters for tamsulosin HCL when it is co-adminstered with second generation dutasteride relative to the currently available commercial dutasteride 0.5 mg and tamsulosin HCL 0.4 mg in the fed state to investigate bioequivalence
PK parameters include: AUC[0-t]), area under the concentration-time curve from time zero extrapolated to infinite time (AUC[0-infinity]) [defaulting to AUC(0-t)

Secondary Outcome Measures

PK profile of dutasteride
PK parameters include: time of occurrence of Cmax (tmax), and negative slope of the terminal phase (lambda) as data permit.
PK profile of tamsulosin HCL
PK parameters include: tmax, lambda, and half life (t1/2)
Clinically significant changes in Vital signs measurements to assess safety and tolerability
Vital signs will include blood pressure and pulse rate measurements
Incidence of adverse events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Clinical laboratory parameter assessment as a measure of safety and tolerability
Laboratory parameters include: hematology, clinical chemistry and urinalysis.

Full Information

First Posted
February 6, 2014
Last Updated
September 11, 2018
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT02058576
Brief Title
Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin HCl Combination Capsule in Fed State
Official Title
A Single-Dose, Randomised, Open-Label, Two-Period Crossover Study to Determine the Bioequivalence of the Second Generation Dutasteride and Tamsulosin HCl Combination Capsule in the Fed State in Healthy Adult Male Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
February 11, 2014 (Actual)
Primary Completion Date
January 2, 2015 (Actual)
Study Completion Date
January 2, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to assess the bioequivalence of the second generation dutasteride and tamsulosin hydrochloride (HCL) combination capsule versus currently available commercial combination of dutasteride 0.5 milligrams (mg) and tamsulosin HCL 0.4 mg capsule in healthy adult male subjects. Subjects in this study will receive either a single oral dose of the second generation dutasteride 0.5 mg and tamsulosin 0.4 mg combination capsule or a single dose of commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg capsule followed by a 28-day washout period both in fed state. The study will enroll approximately 92 healthy adult male subjects in order to complete approximately 76 evaluable subjects. The total duration of a subject's involvement in this study is anticipated to be approximately 12 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Urologic Diseases
Keywords
combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg, Tamsulosin, healthy subject, bioequivalence, GI198745, dutasteride, tamsulosin hydrochloride

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
77 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sequence AB
Arm Type
Experimental
Arm Description
Subjects will receive Treatment A (commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg) in period 1 and Treatment B (combination of second generation dutasteride 0.5 mg and tamsulosin HCL 0.4 mg combination) in period 2 orally once daily under fed condition.
Arm Title
Sequence BA
Arm Type
Experimental
Arm Description
Subjects will be randomized to receive Treatment B (combination of second generation dutasteride 0.5 mg and tamsulosin HCl 0.4 mg combination) in period 1 and Treatment A (commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg) in period 2 orally once daily under fed condition.
Intervention Type
Drug
Intervention Name(s)
Commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg
Intervention Description
Commercially available, orange and brown, hard shell capsule, administered orally as a single dose on Day 1 under fed condition.
Intervention Type
Drug
Intervention Name(s)
Second generation dutasteride 0.5 mg and tamsulosin HCL 0.4 mg combination capsule
Intervention Description
Orange and brown, hard shell capsule, administered orally, as a single-dose on Day 1 under fed condition
Primary Outcome Measure Information:
Title
Pharmacokinetic profile for second generation dutasteride when co-administered with tamsulosin HCL relative to the currently available commercial combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg in the fed state to investigate bioequivalence
Description
PK parameters include: area under the concentration-time curve from time zero to last time of quantifiable concentration within a subject (AUC [0-t]), and maximum observed concentration (Cmax) as data permit.
Time Frame
PK blood samples will be collected at pre-dose, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72 hour post dose in each period.
Title
Composite of PK parameters for tamsulosin HCL when it is co-adminstered with second generation dutasteride relative to the currently available commercial dutasteride 0.5 mg and tamsulosin HCL 0.4 mg in the fed state to investigate bioequivalence
Description
PK parameters include: AUC[0-t]), area under the concentration-time curve from time zero extrapolated to infinite time (AUC[0-infinity]) [defaulting to AUC(0-t)
Time Frame
PK blood samples will be collected at pre-dose, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72 hour post dose in each period.
Secondary Outcome Measure Information:
Title
PK profile of dutasteride
Description
PK parameters include: time of occurrence of Cmax (tmax), and negative slope of the terminal phase (lambda) as data permit.
Time Frame
PK blood samples will be collected at pre-dose, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72 hour post dose in each period.
Title
PK profile of tamsulosin HCL
Description
PK parameters include: tmax, lambda, and half life (t1/2)
Time Frame
PK blood samples will be collected at pre-dose, 0, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 6.5, 7, 7.5, 8, 10, 12, 16, 24, 48, 72 hour post dose in each period.
Title
Clinically significant changes in Vital signs measurements to assess safety and tolerability
Description
Vital signs will include blood pressure and pulse rate measurements
Time Frame
Baseline (screening) and up to 33 days.
Title
Incidence of adverse events (AEs)
Description
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame
Up to 48 days
Title
Clinical laboratory parameter assessment as a measure of safety and tolerability
Description
Laboratory parameters include: hematology, clinical chemistry and urinalysis.
Time Frame
Up to 33 days

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Males who are 18 to 50 years of age, inclusive. Weight range 55 to 95 kg (inclusive) and body mass index (BMI) 18 to 30 kilogram/meter^2 (kg/m^2) (inclusive). Healthy subjects defined as individuals who are free from clinically significant illness or disease as determined by the investigator based on their medical history, physical examination, vital signs, laboratory studies, and electrocardiograms (ECGs). Single QTc <450 millisecond (msec) or QTc <480 msec in subjects with Bundle Branch Block, no clinically relevant abnormal finding on the screening ECG. Serum creatinine <1.5 x upper limit of normal (ULN) at screening. CYP2D6 Extensive Metabolizers only at screening Willing and able to give written informed consent Able to swallow and retain oral medication. Male subjects with female partners of child-bearing potential must agree to use 1 of the contraception methods. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), and bilirubin <=1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). Exclusion Criteria: 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 any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with a subject's safety, or interfere with the subject's ability to follow indications or study procedures, or the interpretation of study results or obtaining informed consent or compliance to study procedures in the opinion of the Investigator or GSK Medical Monitor. History of myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident prior to Screening visit; or diabetes or peptic ulcer disease which is uncontrolled by medical management. History of breast cancer or clinical breast examination finding suggestive of malignancy, malignancy within the past 5 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. Subjects 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. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. Positive human immunodeficiency virus (HIV) test at screening. Use of prescription or non-prescription drugs. Strong CYP3A4 inhibitors (e.g. ketoconazole) and/or strong CYP2D6 inhibitors (e.g. paroxetine) usage throughout the study. History of sensitivity to heparin or heparin-induced thrombocytopenia. History of regular alcohol consumption exceeding 21 drinks/week for men (1 unit is equivalent to 8 gram of alcohol: a half-pint (equivalent to 240 millilitre [mL]) of beer, 1 glass (equivalent to 125 mL) of wine or 1 (equivalent to 25 mL) measure of spirits) within 6 months of screening. 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 the completion of the final PK sample during each period. A positive urine drug or alcohol screen result at screening and at Day -1. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids, and benzodiazepines. 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. 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, exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. 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 or presence of allergy, intolerance, contraindication or sensitivity to alpha blockers (e.g., tamsulosin), or 5 alpha reductase inhibitors (e.g., dutasteride) or drugs of these therapeutic classes, soya or peanuts, or any ingredients of commercially available combination of dutasteride 0.5 mg and tamsulosin HCL 0.4 mg, or a history of drug or other allergy (including true sulfonamide allergy) that, in the opinion of the investigator, contraindicates your participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Belfast
ZIP/Postal Code
BT9 6AD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Access Criteria
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD Sharing URL
https://clinicalstudydatarequest.com

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Bioequivalence Study of the Second Generation Dutasteride and Tamsulosin HCl Combination Capsule in Fed State

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