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A Study to Investigate the Safety Tolerability Pharmacokinetics, and Pharmacodynamics of Inhaled and Intravenous GSK2862277 in Healthy Volunteers

12 mei 2017 bijgewerkt door: GlaxoSmithKline

A Three Part, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Repeat Doses of Inhaled and Intravenous GSK2862277 in Healthy Volunteers

This will be a 3 part study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat doses of GSK2862277 administered via inhalation (IH) or intravenous (IV) routes in healthy subjects.

Part 1 of this study will involve an initial assessment of safety, tolerability and pharmacokinetics of GSK286227, via single escalating intravenous doses, compared to a predecessor molecule, GSK1995057. After completion of Part 1 an interim data review will occur which will assess key comparability criteria to inform progression to Part 2 of the study.

Part 2 of the study will involve single doses of GSK2862277 at a level predicted to be at or close to therapeutic dose levels. Part 2 will investigate both intravenous and inhaled routes of administration, in sequential manner, respectively. An interim data review will also occur after completion of Part 2, where all data accumulated previously will be assessed to examine appropriateness to progress to Part 3.

Part 3 of the study will involve 5 days of repeat dosing via both inhaled and intravenous routes using the same dose administered in Part 2.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

54

Fase

  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigd Koninkrijk
    • Middlesex
      • Harrow, Middlesex, Verenigd Koninkrijk, HA13UJ
        • GSK Investigational Site

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 65 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Ja

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  • Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • 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 parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Subject is positive at screening for HAVH autoantibodies against GSK1995057 (Part 1 only).
  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • A positive pre-study drug/alcohol screen.
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Exclusion Criteria:

  • A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
  • A positive pre-study drug/alcohol screen.
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Enkel

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Part 1: Cohort 1a
Single IV dose of GSK2862277 as a continuous infusion over 2 hours.
Geneesmiddel: Single IV dose of GSK2862277
GSK2862277 solution available in a 40 mg vial for IV administration.
Experimenteel: Part 1: Cohort 1b
Single IV dose of GSK2862277 as a continuous infusion over 3 hours.
Geneesmiddel: Single IV dose of GSK2862277
GSK2862277 solution available in a 40 mg vial for IV administration.
Experimenteel: Part 1: Cohort 1c
Single IV dose of GSK2862277 as a continuous infusion over 3 hours.
Geneesmiddel: Single IV dose of GSK2862277
GSK2862277 solution available in a 40 mg vial for IV administration.
Experimenteel: Part 2: Cohort 2a GSK2862277
Single IV dose of GSK2862277 as a continuous infusion over 1 hour.
Geneesmiddel: Single IV dose of GSK2862277
GSK2862277 solution available in a 40 mg vial for IV administration.
Experimenteel: Part 2: Cohort 2a Placebo
Matching placebo will be administered as a continuous IV infusion over 1 hour.
Geneesmiddel: Matching placebo single dose IV infusion
Matching placebo solution available for IV administration.
Experimenteel: Part 2: Cohort 2b GSK2862277
Single IH dose of GSK2862277.
Geneesmiddel: Single IH dose of GSK2862277
GSK2862277 nebulised solution available in a 40 mg vial for IH administration.
Experimenteel: Part 2: Cohort 2b Placebo
Matching placebo will be administered.
Geneesmiddel: Matching placebo single dose IH
Matching placebo nebulised solution available for IH administration.
Experimenteel: Part 3: Cohort 3a GSK2862277
IV dose of GSK2862277 (decided from Part 2) as a continuous infusion over 1 hour for daily 5 days.
Geneesmiddel: Repeat IV dose of GSK2862277
GSK2862277 solution available in a 40 mg vial for IV administration.
Experimenteel: Part 3: Cohort 3a Placebo
Matching placebo will be administered as IV infusion over 1 hour daily for 5 days.
Geneesmiddel: Matching placebo repeat dose IV infusion
Matching placebo solution available for IV administration.
Experimenteel: Part 3: Cohort 3b GSK2862277
Repeat IH dose of GSK2862277 (decided from Part 2) daily for 5 days.
Geneesmiddel: Repeat IH dose selected of GSK2862277 from Part 2
GSK2862277 nebulised solution available in a 40 mg vial for IH administration.
Experimenteel: Part 3: Cohort 3b Placebo
Matching placebo will be administered as IH daily for 5 days.
Geneesmiddel: Matching placebo repeat dose IH
Matching placebo nebulised solution available for IH administration.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by number of subjects with adverse events (AE)s in Part 1 and Part 2
Tijdsspanne: Up to 42 days
Safety and tolerability parameters will include recording of adverse events (AEs), throughout the study.
Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by number of subjects with AEs in Part 3
Tijdsspanne: Up to 42 days
Safety and tolerability parameters will include recording of AEs, throughout the study.
Up to 42 days
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by laboratory tests in Part 1 and Part 2
Tijdsspanne: Up to 42 days
Laboratory tests will include haemogram, clinical chemistry, urine examination.
Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 as assessed by laboratory tests in Part 3
Tijdsspanne: Up to 42 days
Laboratory tests will include haemogram, clinical chemistry, urine examination.
Up to 42 days
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by vital signs in Part 1 and Part 2
Tijdsspanne: Up to 42 days
Vital signs will include blood pressure (BP), heart rate respiration rate and body temperature.
Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by vital signs in Part 3
Tijdsspanne: Up to 42 days
Vital signs will include BP, heart rate respiration rate and body temperature.
Up to 42 days
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by ECG in Part 1 and Part 2
Tijdsspanne: Up to 42 days
Safety data will include electrocardiogram (ECG) readings obtained at each timepoint during the study.
Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by ECG in Part 3
Tijdsspanne: Up to 42 days
Safety data will include ECG readings obtained at each timepoint during the study.
Up to 42 days
Safety and tolerability of single IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 1 and Part 2
Tijdsspanne: Up to 42 days
Spirometry monitoring will include forced expiratory volume in one second (FEV1) and forced vital capacity (FVC).
Up to 42 days
Safety and tolerability of repeat IV or IH dose of GSK2862277 assessed by spirometry monitoring in Part 3
Tijdsspanne: Up to 42 days
Spirometry monitoring will include FEV1 and FVC.
Up to 42 days
Safety and tolerability of single IV dose of GSK2862277 as assessed by measurement of plasma cytokines in Part 1
Tijdsspanne: Up to 42 days
Blood samples will be collected for assessment of plasma cytokines.
Up to 42 days
Immunogenicity in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Tijdsspanne: Up to 60 days
Presence of anti GSK2862277 binding antibodies will be evaluated.
Up to 60 days
Immunogenicity in subjects receiving repeat IV or IH dose of GSK2862277 in Part 3
Tijdsspanne: Up to 60 days
Presence of anti GSK2862277 binding antibodies will be evaluated.
Up to 60 days

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Tijdsspanne: Up to 48 hours post dose
The blood samples will be collected for plasma concentrations of GSK2862277.
Up to 48 hours post dose
PK parameters in subjects receiving repeat IV dose of GSK2862277 in Part 3 Cohort 3a
Tijdsspanne: Up to 48 hours post last dose
The blood samples will be collected for plasma concentrations of GSK2862277.
Up to 48 hours post last dose
PK parameters in subjects receiving repeat IH dose of GSK2862277 in Part 3 Cohort 3b
Tijdsspanne: Up to 48 hours post last dose
The blood samples will be collected for plasma concentrations of GSK2862277
Up to 48 hours post last dose
PK parameters in subjects receiving single IV dose of GSK2862277 in Part 1
Tijdsspanne: Up to 48 hours post last dose
The PK parameters will be compared with historic GSK1995057 PK data in Part 1
Up to 48 hours post last dose
Pharmacodynamic and immune function biomarkers in serum of subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Tijdsspanne: Up to 48 hours post last dose
The pharmacodynamic and immune function biomarkers in serum.
Up to 48 hours post last dose
Pharmacodynamic and immune function biomarkers in serum of subjects receiving repeat IV or IH dose of GSK2862277in Part 3
Tijdsspanne: Up to 48 hours post last dose
The pharmacodynamic and immune function biomarkers in serum.
Up to 48 hours post last dose
Change from baseline in IL-8 expression in ex vivo WBA in subjects receiving single IV 0.05 mg/kg dose of GSK2862277 in Part 1 in Cohort1c
Tijdsspanne: Up to 12 hours post dose
IL-8 expression in ex vivo whole blood essay (WBA).
Up to 12 hours post dose
Composite of urine parameters in subjects receiving single IV 2 mg/kg dose of GSK2862277 in Part 2 in Cohort 2a
Tijdsspanne: Up to 48 hours post dose
The urine samples will be collected for urine concentrations of GSK2862277.
Up to 48 hours post dose

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

GlaxoSmithKline

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

22 februari 2013

Primaire voltooiing (Werkelijk)

25 oktober 2013

Studie voltooiing (Werkelijk)

25 oktober 2013

Studieregistratiedata

Eerst ingediend

14 februari 2013

Eerst ingediend dat voldeed aan de QC-criteria

21 maart 2013

Eerst geplaatst (Schatting)

26 maart 2013

Updates van studierecords

Laatste update geplaatst (Werkelijk)

15 mei 2017

Laatste update ingediend die voldeed aan QC-criteria

12 mei 2017

Laatst geverifieerd

1 mei 2017

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 116343

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

JA

Beschrijving IPD-plan

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

Bestudeer gegevens/documenten

  1. Specificatie gegevensset
    Informatie-ID: 116343
    Informatie opmerkingen: For additional information about this study please refer to the GSK Clinical Study Register
  2. Gegevensset individuele deelnemers
    Informatie-ID: 116343
    Informatie opmerkingen: For additional information about this study please refer to the GSK Clinical Study Register
  3. Klinisch onderzoeksrapport
    Informatie-ID: 116343
    Informatie opmerkingen: For additional information about this study please refer to the GSK Clinical Study Register
  4. Geannoteerd casusrapportformulier
    Informatie-ID: 116343
    Informatie opmerkingen: For additional information about this study please refer to the GSK Clinical Study Register
  5. Formulier geïnformeerde toestemming
    Informatie-ID: 116343
    Informatie opmerkingen: For additional information about this study please refer to the GSK Clinical Study Register
  6. Statistisch analyseplan
    Informatie-ID: 116343
    Informatie opmerkingen: For additional information about this study please refer to the GSK Clinical Study Register
  7. Leerprotocool
    Informatie-ID: 116343
    Informatie opmerkingen: For additional information about this study please refer to the GSK Clinical Study Register

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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