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

NCT00537654 | Completed Phase 1

• 1 other identifier: ARI109882
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostatic Hyperplasia

Keywords

benign prostatic hyperplasia,; AVODART,; FLOMAX

Outcome Measures

Primary Outcomes (12)

• Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma tamsulosin in fed state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Area under the curve from time zero to infinity (AUC[0-inf]) of plasma tamsulosin in fed state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Concentration maximum (Cmax) of plasma tamsulosin in fed state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma dutasteride in fed state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Area under the curve (AUC) from time zero to 72 hours (AUC[0-72]) of plasma dutasteride in fed state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Concentration maximum (Cmax) of plasma dutasteride in fed state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma tamsulosin in fasted state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Area under the curve from time zero to infinity (AUC[0-inf]) of plasma tamsulosin in fasted state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Concentration maximum (Cmax) of plasma tamsulosin in fasted state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Area under the curve (AUC) from time zero to 24 hours (AUC[0-24]) of plasma dutasteride in fasted state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Area under the curve (AUC) from time zero to 72 hours (AUC[0-72]) of plasma dutasteride in fasted state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Concentration maximum (Cmax) of plasma dutasteride in fasted state

  Plasma samples will be collected at indicated time points

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

Secondary Outcomes (10)

• Concentration minimum (Cmax) of plasma tamsulosin

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Time to maximum observed plasma drug concentration (tmax) of tamsulosin and dutasteride

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Elimination half-life (t1/2) of tamsulosin and dutasteride

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Negative slope of the terminal phase of tamsulosin and dutasteride

  Pre-dose and post dose at 1,2,3,4,5,6,7,8,10,12,16,24,36,48,72hrs

• Number of subjects with adverse event (AE) and serious adverse event (SAE).

  Up to 18 weeks

Study Arms (2)

Fasted state

EXPERIMENTAL

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; Drug: Treatment sequence D

Fed state

EXPERIMENTAL

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; Drug: Treatment sequence B

Interventions

Treatment sequence A DRUG

Commercially available tamsulosin hydrochloride 0.4 mg and dutasteride 0.5 mg in a fed state

Fed state

Treatment sequence B DRUG

Fixed dose combination formulation of dutasteride and tamsulosin hydrochloride (0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride) in a fed state

Fed state

Treatment sequence C DRUG

Commercially available tamsulosin hydrochloride 0.4 mg and dutasteride 0.5 mg in a fasted state

Fasted state

Treatment sequence D DRUG

Fixed dose combination formulation of dutasteride and tamsulosin hydrochloride (0.5 mg dutasteride, 0.4 mg tamsulosin hydrochloride) in a fasted state

Fasted state

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Evansville, Indiana, 47714, United States

Location

GSK Investigational Site

Austin, Texas, 78752, United States

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study ARI109882 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Prostatic Hyperplasia

Condition Hierarchy (Ancestors)

Prostatic Diseases; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2007
• First Posted: October 1, 2007
• Study Start: October 18, 2007
• Primary Completion: February 22, 2008
• Study Completion: February 22, 2008
• Last Updated: August 17, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (2)