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

12. maj 2017 opdateret af: 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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

54

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 65 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ja

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Enkelt

Våben og indgreb

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

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Up to 60 days
Presence of anti GSK2862277 binding antibodies will be evaluated.
Up to 60 days

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Pharmacokinetic (PK) parameters in subjects receiving single IV or IH dose of GSK2862277 in Part 1 and Part 2
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Up to 48 hours post dose
The urine samples will be collected for urine concentrations of GSK2862277.
Up to 48 hours post dose

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

GlaxoSmithKline

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

22. februar 2013

Primær færdiggørelse (Faktiske)

25. oktober 2013

Studieafslutning (Faktiske)

25. oktober 2013

Datoer for studieregistrering

Først indsendt

14. februar 2013

Først indsendt, der opfyldte QC-kriterier

21. marts 2013

Først opslået (Skøn)

26. marts 2013

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

15. maj 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

12. maj 2017

Sidst verificeret

1. maj 2017

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 116343

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

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

Studiedata/dokumenter

  1. Datasætspecifikation
    Informations-id: 116343
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  2. Individuelt deltagerdatasæt
    Informations-id: 116343
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  3. Klinisk undersøgelsesrapport
    Informations-id: 116343
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  4. Annoteret sagsbetænkningsformular
    Informations-id: 116343
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  5. Formular til informeret samtykke
    Informations-id: 116343
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  6. Statistisk analyseplan
    Informations-id: 116343
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
  7. Studieprotokol
    Informations-id: 116343
    Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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