Clinical trial NCT00537654: A Study To Compare Giving AVODART And FLOMAX Together Or In A Combination Capsule In The Fed And Fasted State
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostatic Hyperplasia
Keywords: benign prostatic hyperplasia,
AVODART,
FLOMAX
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-10-01
Enrollment: 81
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma tamsulosin in fed state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Area under the curve from time zero to infinity (AUC[0-inf]) of plasma tamsulosin in fed state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Concentration maximum (Cmax) of plasma tamsulosin in fed state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma dutasteride in fed state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Area under the curve (AUC) from time zero to 72 hours (AUC[0-72]) of plasma dutasteride in fed state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Concentration maximum (Cmax) of plasma dutasteride in fed state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma tamsulosin in fasted state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Area under the curve from time zero to infinity (AUC[0-inf]) of plasma tamsulosin in fasted state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Concentration maximum (Cmax) of plasma tamsulosin in fasted state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma dutasteride in fasted state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Area under the curve (AUC) from time zero to 72 hours (AUC[0-72]) of plasma dutasteride in fasted state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Concentration maximum (Cmax) of plasma dutasteride in fasted state
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
Secondary outcomes:
measure: Concentration minimum (Cmax) of plasma tamsulosin
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Time to maximum observed plasma drug concentration (tmax) of tamsulosin and dutasteride
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Elimination half-life (t1/2) of tamsulosin and dutasteride
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Negative slope of the terminal phase of tamsulosin and dutasteride
timeFrame: Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs
measure: Number of subjects with adverse event (AE) and serious adverse event (SAE).
timeFrame: Up to 18 weeks
measure: Number of subjects with abnormal clinical laboratory parameters
timeFrame: Up to 18 weeks
measure: Number of subjects with abnormal hematology laboratory parameters
timeFrame: Up to 18 weeks
measure: Number of subjects with abnormal urinalysis
timeFrame: Up to 18 weeks
measure: Blood pressure assessment as a measure of safety
timeFrame: Up to 18 weeks
measure: Measurement of pulse rate as a measure of safety
timeFrame: Up to 18 weeks
Other outcomes:
Locations:
city: Evansville
country: United States
facility: GSK Investigational Site
state: Indiana
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: