Assessment of Repeat Ascending Doses of GSK2018682 in Healthy Volunteers (P1A114347)
A Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Repeat Ascending Doses of GSK2018682 (S1P1 Agonist) in Healthy Volunteers
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
New South Wales
-
Randwick, New South Wales, Australien, 2031
- GSK Investigational Site
-
-
South Australia
-
Adelaide, South Australia, Australien, 5000
- GSK Investigational Site
-
-
Western Australia
-
Nedlands, Western Australia, Australien, 6009
- GSK Investigational Site
-
-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- Females must be of non-childbearing potential.
- BMI within the range 19 - 29 kg/m2 (inclusive).
Exclusion Criteria:
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Were participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Other exclusion criteria to be detailed at the time of physical screening by the Investigator
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Crossover opgave
- Maskning: Enkelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Aktiv komparator: GSK2018682
Active Drug
|
Active Drug
|
|
Placebo komparator: Placebo -kontrol
Placebo
|
Placebo
|
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
To investigate the safety and tolerability of repeat oral doses of GSK2018682 in healthy volunteers (males and females of non-childbearing potential)
Tidsramme: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
Adverse event monitoring, Laboratory parameters (haematology, clinical chemistry, urinalysis), Ophthalmic examination
|
Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
|
To investigate effects of repeat oral doses of GSK2018682 on heart rate and blood pressure in healthy volunteers
Tidsramme: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
12-lead ECG, Telemetry ECG, Holter ECG, Vital signs (systolic and diastolic blood pressure, heart rate, respiratory rate, body temperature), Ambulatory blood pressure monitoring
|
Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
|
To investigate effects of repeat oral doses of GSK2018682 on lung function in healthy volunteers
Tidsramme: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
FEV1 obtained via spirometry
|
Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
|
To investigate the pharmacokinetics of repeat oral doses of GSK2018682 in healthy volunteers
Tidsramme: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
Peak blood concentration, Time of peak blood concentration, Area under the blood concentration-time curve over the 24-hour dose interval and area under the blood concentration-time curve from time-zero extrapolated to infinite time, Accumulation ratio, Terminal half-life, Apparent oral clearance, Through concentration
|
Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
|
To characterize the metabolism of GSK2018682
Tidsramme: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
GSK2018682 bile metabolites, GSK2018682 whole blood metabolites
|
Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
|
Evaluate the effect of repeat oral doses of GSK2018682 on lymphocytes in healthy volunteers
Tidsramme: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
% Change from baseline in absolute lymphocyte counts (ALC), % Change from baseline in subsets CD3+ [CD4+ and CD8+], CD19+, CD16+/CD56+ counts, % Change from baseline in further defined functional T cell subsets (naïve, central memory, effector memory and regulatory T cells)
|
Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
|
To explore the PK/PD relationship between blood concentrations and changes in vital signs and ECG parameters
Tidsramme: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
PK/PD model with parameters of the models will be determined that best describe the relationship between blood concentrations of GSK2018682 and vital signs and ECG parameters
|
Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
|
To explore the PK/PD relationship between blood concentrations of GSK2018682 and reduction in lymphocyte counts
Tidsramme: Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
PK/PD model with parameters of the models will be determined that best describe the relationship between blood concentrations of GSK2018682 and reduction ALC and subset counts CD3+ [CD4+ and CD8+], CD19+, CD16+/CD56+ and further defined functional T cell subsets (naïve, central memory, effector memory and regulatory T cells)
|
Participants will be followed and monitored for the duration of their hospital stay. The longest duration of participation in the study will be approximately 13 weeks
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- 114347
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
Studiedata/dokumenter
-
Individuelt deltagerdatasæt
Informations-id: 114347Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
-
Annoteret sagsbetænkningsformular
Informations-id: 114347Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
-
Formular til informeret samtykke
Informations-id: 114347Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
-
Studieprotokol
Informations-id: 114347Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
-
Statistisk analyseplan
Informations-id: 114347Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
-
Klinisk undersøgelsesrapport
Informations-id: 114347Oplysningskommentarer: For additional information about this study please refer to the GSK Clinical Study Register
-
Datasætspecifikation
Informations-id: 114347Oplysningskommentarer: 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 .