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A Study To Compare Giving AVODART And FLOMAX Together Or In A Combination Capsule In The Fed And Fasted State

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00537654
First received: September 28, 2007
Last updated: March 10, 2017
Last verified: March 2017
  Purpose
This study will be an open-label, randomized, single dose, three way partial crossover study in healthy male subjects. The aim of the study is to evaluate bioequivalence of a fixed dose combination (FDC) capsule of dutasteride and tamsulosin hydrochloride (HCl) (0.5 milligram [mg]/0.4 mg) relative to co-administration of dutasteride 0.5 mg capsules and tamsulosin hydrochloride 0.4 mg tablets in both the fed and fasted states. Approximately 98 healthy adult male subjects will be enrolled into the study. Subjects will receive single oral doses in 3 treatment periods and be randomized to one of twelve different treatment sequences (ABC, ACB, BAC, BCA, CAB, CBA, ABD, ADB, BAD, BDA, DAB, DBA) wherein A= commercially available tamsulosin hydrochloride 0.4 mg and dutasteride 0.5 mg in a fed state, B= fixed dose combination formulation of dutasteride and tamsulosin hydrochloride (0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride) in a fed state, C= commercially available tamsulosin hydrochloride 0.4 mg and dutasteride 0.5 mg in a fasted state, D= fixed dose combination formulation of dutasteride and tamsulosin hydrochloride (0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride) in a fasted state. Each treatment period will be separated by a minimum 28 day washout period. The total duration of a subject's involvement in this study is approximately 15-18 weeks.

Condition Intervention Phase
Prostatic Hyperplasia
Drug: Treatment sequence A
Drug: Treatment sequence B
Drug: Treatment sequence C
Drug: Treatment sequence D
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: An Open-Label, Randomized, Single Dose Three-Period Partial Crossover Study to Determine the Bioequivalence and Food Effect of a Combination Capsule Formulation of Dutasteride and Tamsulosin Hydrochloride (0.5mg/0.4mg) Compared to Concomitant Dosing of AVODART™ 0.5mg and Flomax 0.4mg Commercial Capsules in Healthy Male Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma tamsulosin in fed state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Area under the curve from time zero to infinity (AUC[0-inf]) of plasma tamsulosin in fed state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Concentration maximum (Cmax) of plasma tamsulosin in fed state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma dutasteride in fed state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Area under the curve (AUC) from time zero to 72 hours (AUC[0-72]) of plasma dutasteride in fed state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Concentration maximum (Cmax) of plasma dutasteride in fed state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma tamsulosin in fasted state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Area under the curve from time zero to infinity (AUC[0-inf]) of plasma tamsulosin in fasted state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Concentration maximum (Cmax) of plasma tamsulosin in fasted state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma dutasteride in fasted state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Area under the curve (AUC) from time zero to 72 hours (AUC[0-72]) of plasma dutasteride in fasted state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Concentration maximum (Cmax) of plasma dutasteride in fasted state [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points


Secondary Outcome Measures:
  • Concentration minimum (Cmax) of plasma tamsulosin [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Time to maximum observed plasma drug concentration (tmax) of tamsulosin and dutasteride [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Elimination half-life (t1/2) of tamsulosin and dutasteride [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Negative slope of the terminal phase of tamsulosin and dutasteride [ Time Frame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs ]
    Plasma samples will be collected at indicated time points

  • Number of subjects with adverse event (AE) and serious adverse event (SAE). [ Time Frame: Up to 18 weeks ]
    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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE.

  • Number of subjects with abnormal clinical laboratory parameters [ Time Frame: Up to 18 weeks ]
    Blood samples will be collected to analyze aspartate aminotransferase (AST), alkaline Phosphatase (ALP), alanine aminotransferase (ALT), creatinine, blood urea nitrogen, creatine kinase, total bilirubin, direct bilirubin, total protein, albumin, glucose, sodium, potassium, calcium

  • Number of subjects with abnormal hematology laboratory parameters [ Time Frame: Up to 18 weeks ]
    Blood samples will be collected to analyze White Blood Cells (WBC), neutrophils, basophils, eosionophils, lymphocytes, monocytes, Red Blood Cells (RBC) count, RBC indices, Day -1average red blood cell size (MCV), hemoglobin amount per red blood cell (MCH) hemoglobin, hematocrit, and platelet count

  • Number of subjects with abnormal urinalysis [ Time Frame: Up to 18 weeks ]
    Urine samples will be collected to analyze specific gravity, pH, glucose, protein, blood and ketones

  • Blood pressure assessment as a measure of safety [ Time Frame: Up to 18 weeks ]
    Systolic and diastolic blood pressure will be measured in a supine position at pre-dose, Days 2, 3, 4,5,6,7,43 and 85 post-dose

  • Measurement of pulse rate as a measure of safety [ Time Frame: Up to 18 weeks ]
    Pulse rate will be measured in a supine position at pre-dose, Days 2, 3, 4,5,6,7,43 and 85 post-dose


Enrollment: 81
Study Start Date: October 2007
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fasted state
Subjects will be required to fast overnight. Subjects will participate in 3 treatment periods and assigned to one of 12 treatment sequences ( ABC, ACB, BAC, BCA, CAB, CBA, ABD, ADB, BAD, BDA, DAB, DBA) in accordance with the randomization schedule. The three treatment periods will be separated by a minimum washout period of 28 days
Drug: Treatment sequence C
Commercially available tamsulosin hydrochloride 0.4 mg and dutasteride 0.5 mg in a fasted state
Drug: Treatment sequence D
Fixed dose combination formulation of dutasteride and tamsulosin hydrochloride (0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride) in a fasted state
Experimental: Fed state
Subjects will be served high fat breakfast 30 minutes prior to dosing. Subjects will participate in 3 treatment periods and assigned to one of 12 treatment sequences ( ABC, ACB, BAC, BCA, CAB, CBA, ABD, ADB, BAD, BDA, DAB, DBA) in accordance with the randomization schedule. The three treatment periods will be separated by a minimum washout period of 28 days
Drug: Treatment sequence A
Commercially available tamsulosin hydrochloride 0.4 mg and dutasteride 0.5 mg in a fed state
Drug: Treatment sequence B
Fixed dose combination formulation of dutasteride and tamsulosin hydrochloride (0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride) in a fed state

Detailed Description:
An Open-Label, Randomized, Single Dose Three-Period Partial Crossover Study to Determine the Bioequivalence and Food Effect of a Combination Capsule Formulation of Dutasteride and Tamsulosin Hydrochloride (0.5mg/0.4mg) Compared to Concomitant Dosing of AVODART 0.5mg and FLOMAX 0.4mg Commercial Capsules in Healthy Male Subjects
  Eligibility

Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • 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, laboratory studies, ECGs, and other tests.
  • Males who are 18 - 45 years of age, inclusive.
  • Weight range 55 - 95 kg (inclusive) and body mass index 19 - 30 kg/m2 (inclusive).
  • Willing and able to give written informed consent, willing to participate for the full duration of the study, and able to understand and follow instructions related to study procedures

Exclusion criteria:

  • Slow metabolizer for CYP2D6 as determined by screening PGx analysis.
  • 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.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within 7 days (or 14 days if the drug is a potential enzyme inducer, such as St. John's Wort) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety.
  • Chronic hepatitis B and C, as evidence by positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody.
  • Positive HIV test at screening.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • History of regular alcohol consumption exceeding 14 drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor) within 6 months of screening. Subjects must be able and willing to abstain from beverages and foods containing alcohol 24 hours prior to and during the dosing day.
  • A positive urine drug or alcohol (Breath test or urine) screen result at screening or check-in..
  • The subject has received an investigational drug or participated in any other research trial within 30 days 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.
  • Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period.
  • History or presence of allergy, intolerance, or contraindication to tamsulosin HCl or AVODART or drugs of this class, or a history of drug or other allergy (including true sulfonamide allergy) that, in the opinion of the physician responsible, contraindicates their participation.
  • Subjects who have consumed the following foods or drinks within 7 days prior to the first dose of study medication or at any time during the clinical phase of the study: grapefruit juice; red wine; grapefruit or cruciferous vegetables (watercress, broccoli, cabbage, Brussels sprouts).
  • QTc ≥ 450 msec at screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00537654

Locations
United States, Indiana
GSK Investigational Site
Evansville, Indiana, United States, 47714
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78752
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: ARI109882
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: ARI109882
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: ARI109882
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: ARI109882
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: ARI109882
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: ARI109882
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: ARI109882
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00537654     History of Changes
Other Study ID Numbers: ARI109882
Study First Received: September 28, 2007
Last Updated: March 10, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:
benign prostatic hyperplasia,
AVODART,
FLOMAX

Additional relevant MeSH terms:
Hyperplasia
Prostatic Hyperplasia
Pathologic Processes
Prostatic Diseases
Genital Diseases, Male
Tamsulosin
Dutasteride
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents
5-alpha Reductase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on April 28, 2017