A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of GSK2256294 in Healthy Young Males and Elderly Subjects
A Study to Evaluate the Effect of Age, Food and Gender on Tolerability and Pharmacokinetics of GSK2256294 Following a Single Oral Administration in Healthy Fed and Fasted Elderly Subjects. This Study Will Also Evaluate the Biliary Metabolites in Healthy Young Males Following a Single Dose of GSK2256294
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Typ studie
Typ studie
Zápis (Aktuální)
Zápis
Fáze
Fáze
- Fáze 1
Kontakty a umístění
Studijní místa
-
-
Maryland
-
Baltimore, Maryland, Spojené státy, 21225
- GSK Investigational Site
-
-
Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Safety - All Cohorts
- 12 lead ECG without any clinically significant abnormality as judged by the Investigator, and ECGs QT duration corrected for heart rate by Fridericia's formula (QTcF) <450 milliseconds (msec) determined by the average of triplicate ECGs.
- Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 2 weeks post-last dose.
- Body weight >=60 kilogram (kg) and body mass index (BMI) within the range 19 - 35 kg per meter square (kg/m^2) (inclusive).
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <=1.5xUpper limit of normal [ULN] (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- 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 outside the reference range for the population being studies may be included only of the Investigator agree that the finding is unlikely to introduce additional risk factors and will not interfere with study procedures. Consultation with the GSK Medical Monitor is required.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Safety - Cohort 2 Only
- A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy [for this definition, "documented" refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records]; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) >40 milli international units per milliliter (mIU/mL) and estradiol <40 picogram per milliliter (pg/mL) (<147 picomole per liter) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods listed in the protocol if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.]
- Other - Cohort 1 Only.
- Cohort 1 only: Male aged between 18 and 45 years of age inclusive, at the time of signing the informed consent.
Cohort 1 only: BP <=130/80.
- Other - Cohort 2 Only
- Cohort 2 only: Male and females (of non-child bearing potential) aged >=60 years of age, at the time of signing the informed consent.
- Cohort 2 only: BP <=160/100.
Exclusion 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.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
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 regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for human immunodeficiency virus (HIV) antibody.
- A positive pre-study drug/alcohol screen.
- Subjects with a history of any type of malignancy with the exception of successfully treated squamous cell cancer of the skin.
- History of sensitivity to the study medication, or components thereof or a history of drug allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicated their participation.
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
|
Experimentální: Cohort 1
Cohort 1 will enrol 8 healthy male volunteers, who will receive a single 10 mg dose of GSK225694 in the fasted state.
|
GSK2256294 is a 5 mg capsule administered orally as a 10 mg dose in the fasted or fed state
|
|
Experimentální: Cohort 2
Cohort 2 will enrol 20 healthy elderly male and female volunteers (10 males and 10 females), who will receive a single 10 mg dose of GSK225694 in the fasted or fed state according to the randomization schedule.
|
GSK2256294 is a 5 mg capsule administered orally as a 10 mg dose in the fasted or fed state
|
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Cohort 2: PK profiles of a single oral dose of GSK2256294
Časové okno: Pre-dose, 15 minutes (min), 30 min, 1 hour (h), 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1) and 24 h (Day 2), 48 h (Day 3) and 72 h (Day 4)
|
PK parameters including area under the concentration-time curve (AUC) and maximum blood concentrations (Cmax), half life (T1/2), time to Cmax (Tmax) following a single oral dose of GSK2256294 administered under fed and fasted conditions in healthy elderly male and female subjects will be estimated
|
Pre-dose, 15 minutes (min), 30 min, 1 hour (h), 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h (Day 1) and 24 h (Day 2), 48 h (Day 3) and 72 h (Day 4)
|
|
Cohort 2: Electrocardiogram (ECG) as a measure of safety and tolerability
Časové okno: Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
|
Twelve-lead ECGs will be obtained as a measure of safety and tolerability
|
Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
|
|
Cohort 2: Adverse events (AEs ) as a measure of safety and tolerability
Časové okno: From the start of study treatment and until approximately 2 weeks after the final dose
|
From the start of study treatment and until approximately 2 weeks after the final dose
|
|
|
Cohort 2: Vital signs as a measure of safety and tolerability
Časové okno: Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
|
Vital sign measurements will include systolic and diastolic blood pressure (BP) and pulse rate
|
Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
|
|
Cohort 2: Laboratory assessments as a measure of safety and tolerability
Časové okno: Screening and follow-up. In addition, clinical chemistry will also be done at 12 h (Day 1) and 24 h (Day 2)
|
Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests
|
Screening and follow-up. In addition, clinical chemistry will also be done at 12 h (Day 1) and 24 h (Day 2)
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Cohort 1: Biliary metabolite profile of GSK2256294
Časové okno: Until 7 hours post-dose on Day 1
|
Bile will be collected for metabolic analysis of GSK2256294 + metabolites via the use of the Entero-Test capsule in healthy male younger subjects
|
Until 7 hours post-dose on Day 1
|
|
Cohort 1: AEs as a measure of safety and tolerability
Časové okno: From the start of study treatment and until approximately 2 weeks after the final dose
|
From the start of study treatment and until approximately 2 weeks after the final dose
|
|
|
Cohort 1: ECG as a measure of safety and tolerability
Časové okno: Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
|
Twelve-lead ECGs will be obtained to assess safety and tolerability
|
Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
|
|
Cohort 1: Vital signs as a measure of safety and tolerability
Časové okno: Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
|
Vital sign measurements will include systolic and diastolic BP and pulse rate
|
Screening, Pre-dose, 30 min, 2 h, 4 h, 6 h and at follow-up
|
|
Cohort 1: Laboratory assessments as a measure of safety and tolerability
Časové okno: Screening and follow-up
|
Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests
|
Screening and follow-up
|
|
Cohort 1 and Cohort 2: AUC, Cmax, t1/2,and Tmax of GSK2256294
Časové okno: Cohort 1: Pre-dose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 7 h, 12 h and 24 h, 48 h, and 72 h; Cohort 2: Pre-dose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 24 h, 48 h and 72 h
|
To compare the pharmacokinetic profiles of single oral doses of GSK2256294 in healthy elderly and healthy younger subjects, and between healthy elderly male and female subjects
|
Cohort 1: Pre-dose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 7 h, 12 h and 24 h, 48 h, and 72 h; Cohort 2: Pre-dose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h and 24 h, 48 h and 72 h
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Publikace a užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Aktuální)
Primární dokončení
Dokončení studie (Aktuální)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
Další identifikační čísla studie
Další identifikační čísla studie
- 117023
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Popis plánu IPD
Studijní data/dokumenty
-
Formulář komentované zprávy o případu
Identifikátor informace: 117023Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Plán statistické analýzy
Identifikátor informace: 117023Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Specifikace datové sady
Identifikátor informace: 117023Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Zpráva o klinické studii
Identifikátor informace: 117023Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Formulář informovaného souhlasu
Identifikátor informace: 117023Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Soubor dat jednotlivých účastníků
Identifikátor informace: 117023Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
-
Protokol studie
Identifikátor informace: 117023Komentáře k informacím: For additional information about this study please refer to the GSK Clinical Study Register
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .