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A Study to Investigate the Safety and Pharmacokinetics of a Single Dose of GSK2256294 in Healthy Young Males and Elderly Subjects

5 maggio 2017 aggiornato da: GlaxoSmithKline

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

This study will investigate the safety and pharmacokinetics (PK) of a single dose of GSK2256294 in healthy young and elderly subjects to explore the effects of food, gender and age on drug exposure. The biliary metabolites in healthy young males will be investigated using the Entero-test after a single oral dose of GSK2256294. This study will be conducted in two cohorts (Cohort 1 and Cohort 2). Cohort 1 is open label in order to characterise the PK profile of GSK2256294 in healthy young males and also to investigate the biliary metabolites of GSK2256294. Cohort 2 uses a crossover design to allow comparison of the PK parameters of GSK2256294 between in the fed and fasted state within subject and also to compare the PK parameters of GSK2256294 between male and female subjects. A washout period of a minimum of 2 weeks has been chosen to allow and adequate washout of GSK2256294.

Panoramica dello studio

Stato

Completato

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

28

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

    • Maryland
      • Baltimore, Maryland, Stati Uniti, 21225
        • GSK Investigational Site

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: 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
Sperimentale: 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

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Cohort 2: PK profiles of a single oral dose of GSK2256294
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Cohort 1: Biliary metabolite profile of GSK2256294
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

31 gennaio 2014

Completamento primario (Effettivo)

27 maggio 2014

Completamento dello studio (Effettivo)

27 maggio 2014

Date di iscrizione allo studio

Primo inviato

5 dicembre 2013

Primo inviato che soddisfa i criteri di controllo qualità

5 dicembre 2013

Primo Inserito (Stima)

10 dicembre 2013

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

9 maggio 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

5 maggio 2017

Ultimo verificato

1 maggio 2017

Maggiori informazioni

Termini relativi a questo studio

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

Descrizione del piano IPD

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Dati/documenti di studio

  1. Modulo di segnalazione del caso annotato
    Identificatore informazioni: 117023
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  2. Piano di analisi statistica
    Identificatore informazioni: 117023
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  3. Specifica del set di dati
    Identificatore informazioni: 117023
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  4. Rapporto di studio clinico
    Identificatore informazioni: 117023
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  5. Modulo di consenso informato
    Identificatore informazioni: 117023
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  6. Set di dati del singolo partecipante
    Identificatore informazioni: 117023
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register
  7. Protocollo di studio
    Identificatore informazioni: 117023
    Commenti informativi: For additional information about this study please refer to the GSK Clinical Study Register

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su GSK2256294

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