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Sikkerhed, tolerabilitet og farmakokinetik (PK) undersøgelse af GSK3494245 hos raske deltagere

8. april 2026 opdateret af: GlaxoSmithKline

En randomiseret, dobbeltblind, placebokontrolleret, første gang i menneskelig undersøgelse for at evaluere sikkerheden, tolerabiliteten og farmakokinetikken af ​​enkeltdoser (i både føde- og fastestater) af GSK3494245 hos raske deltagere

Dette er en fase 1, dobbeltblind, randomiseret, placebokontrolleret, første gang i human (FTIH) undersøgelse for at vurdere sikkerheden, tolerabiliteten og PK af en enkelt dosis GSK3494245. Undersøgelsen vil bestå af 3 kohorter, udført på en sekventiel måde. Kohorte 1 og 2 vil bestå af en enkelt stigende dosis (SAD), crossover design, hvor hver deltager vil modtage maksimalt 3 stigende orale doser af GSK3494245 og 1 placebo dosis under fastende forhold. Ved hvert dosisniveau vil GSK3494245 og placebo blive administreret i et forhold på 3:1 inden for hver periode i henhold til randomiseringsskemaet på en blind måde. Kohorte 3 vil bestå af en 2-vejs overkrydsning, som inkluderer 1 doseringsregime under faste og derefter fodrede forhold og 1 regime under foder og derefter fastende forhold i forholdet 1:1. De fodrede forhold vil undersøge effekten af ​​sikkerhed, tolerabilitet og PK af en enkelt dosis GSK3494245 efter fødevareadministration.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

The study originally planned to include 2 parts - a single ascending doses (SAD) part and a multiple ascending doses (MAD) part, incorporating a food effect component to investigate the influence of food on the PK of GSK3494245. However, only the SAD part was conducted due to a decision to terminate the study early.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

59

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 50 år (Voksen)

Tager imod sunde frivillige

Ja

Beskrivelse

Inklusionskriterier

  • Deltageren skal være 18 til <=50 år på tidspunktet for underskrivelsen af ​​det informerede samtykke.
  • Deltageren skal være rask som bestemt af efterforskeren eller den medicinsk kvalificerede udpegede baseret på en medicinsk evaluering, herunder sygehistorie, fysisk undersøgelse, laboratorietest og hjerteovervågning. En deltager med en klinisk abnormitet eller laboratorieparametre, som ikke er specifikt anført i inklusions- eller eksklusionskriterierne, uden for det normale referenceområde for den population, der undersøges, kan kun inkluderes, hvis investigatoren i samråd med den medicinske monitor ( om nødvendigt) acceptere og dokumentere, at resultatet sandsynligvis ikke vil introducere yderligere risikofaktorer og ikke vil forstyrre undersøgelsesprocedurerne.
  • Kropsvægt >=50 kilogram (kg) og kropsmasseindeks (BMI) inden for intervallet 18,5-28 kilogram pr. kvadratmeter kvadrat (kg/m^2) (inklusive).
  • Kun mandlige deltagere. En mandlig deltager med en kvindelig partner med reproduktionspotentiale skal acceptere at bruge prævention i interventionsperioden og i mindst 90 dage efter den sidste dosis af undersøgelsesbehandlingen og afstå fra at donere sæd i denne periode.
  • I stand til at give underskrevet informeret samtykke, som omfatter overholdelse af kravene og begrænsninger, der er anført i Informed Consent Form (ICF) og protokollen.

Eksklusionskriterier

  • Anamnese eller tilstedeværelse af kardiovaskulære, respiratoriske, lever-, nyre-, gastrointestinale, endokrine, hæmatologiske eller neurologiske lidelser, der er i stand til væsentligt at ændre absorption, metabolisme eller eliminering af lægemidler; udgør en risiko ved at tage undersøgelsesbehandlingen; eller forstyrre fortolkningen af ​​data.
  • Unormalt blodtryk, som bestemt af efterforskeren.
  • Tidligere historie om leishmaniasis.
  • Alaninaminotransferase (ALT) større end 1,5 gange øvre normalgrænse (ULN).
  • Total bilirubin større end 1,5 gange ULN (isoleret bilirubin større end 1,5 gange ULN er acceptabelt, hvis total bilirubin er fraktioneret og direkte bilirubin mindre end 35 procent [%]).
  • Aktuel eller kronisk anamnese med leversygdom eller kendte lever- eller galdeabnormiteter (med undtagelse af Gilberts syndrom eller asymptomatiske galdesten).
  • Aktuel eller historie med klinisk signifikant gastritis eller gastroduodenale ulcera eller regelmæssig brug af ikke-steroide antiinflammatoriske lægemidler (NSAID).
  • Indtagelse af mere end 14 enheder/uge alkohol (mandlige frivillige).
  • Aktuel eller historie med ændring i smag eller lugt uden nogen plausibel klinisk forklaring baseret på investigators kliniske vurdering.
  • QTc større end 450 millisekunder (msec) baseret på gennemsnit af tredobbelte EKG'er.
  • Bølgeformabnormiteter, herunder for tidlig ventrikulær kontraktion (PVC) tripletter og mere end 500 enkelt PVC'er på 24 timer, eller andre abnormiteter efter investigators skøn.
  • Sygehistorie med hjertearytmier eller hjertesygdom eller en familie eller personlig historie med langt QT-syndrom.
  • Tidligere eller påtænkt brug af håndkøbsmedicin eller receptpligtig medicin, herunder naturlægemidler, NSAID'er, protonpumpehæmmere (PPI'er) eller antihistamin 2-receptor (H2) antagonister inden for 7 dage (eller 14 dage, hvis lægemidlet er et potentielt enzym inducer) eller 5 halveringstider (alt efter hvad der er længst) før dosering. Anden samtidig medicinering kan overvejes fra sag til sag af investigator i samråd med den medicinske monitor. Paracetamol er tilladt (begrænset til <=2 gram/dag).
  • Deltagelse i undersøgelsen, der ville resultere i tab af blod eller blodprodukter på over 500 milliliter (ml) inden for en 56-dages periode.
  • Eksponering for mere end 4 nye kemiske enheder inden for 12 måneder før den første doseringsdag.
  • Nuværende tilmelding eller tidligere deltagelse inden for de sidste 30 dage før underskrivelse af samtykke i enhver anden klinisk undersøgelse, der involverer en undersøgelsesintervention eller enhver anden form for medicinsk forskning.
  • Nuværende tilmelding eller tidligere deltagelse i denne kliniske undersøgelse.
  • Deltagere med nyrefunktion defineret som Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) med en aldersegnet glomerulær filtrationshastighed (GFR) <90 (milliliter pr. minut pr. 1,73 kvadratmeter [mL/min/1,73m^2]).
  • Screening af urin albumin:kreatinin-forhold >30 milligram pr. gram (mg/g) (>3 milligram pr. millimol [mg/mmol])
  • Tilstedeværelse af hepatitis B overfladeantigen (HBsAg) testresultat ved screening.
  • Positivt testresultat for hepatitis C antistof ved screening.
  • Positivt resultat af hepatitis C-ribonukleinsyre (RNA) test ved screening.
  • Positiv human immundefekt virus (HIV) antistoftest.
  • Tilstedeværelse af klinisk signifikant hæmaturi og/eller proteinuri.
  • Kulilteniveauer, der indikerer rygning eller historie eller regelmæssig brug af tobak eller nikotinholdige produkter inden for 3 måneder før screening.
  • Positiv lægemiddel/alkoholskærm før undersøgelse.
  • Regelmæssig brug af kendte misbrugsstoffer.
  • Kun fødevareeffekt kohorte 3: Deltageren må ikke have nogen diætrestriktioner (f.eks. laktoseintolerance) eller manglende evne til at spise gelatine eller et tilpasset standardmåltid (inkluderer 35-40 % fedtindhold).
  • Fødevareeffekt kun kohorte 3: Anamnese med galdeblærekirurgi eller fjernelse af galdeblære eller historie med en akut sygdomstilstand (f.eks. kolelithiasis) inden for 14 dage før modtagelse af undersøgelsesbehandlingen.
  • Deltagerne må ikke have rejst til et område (som bestemt af investigator) med en høj forekomst af leishmaniale/parasitære infektioner i de 6 måneder før screening eller har til hensigt at gøre det i de 3 måneder efter den sidste dosis af undersøgelsesbehandlingen.
  • Følsomhed over for en hvilken som helst af undersøgelsesbehandlingerne, eller komponenter deraf, eller lægemidler eller anden allergi, der efter Investigator eller GSK Medical Monitors mening kontraindicerer deltagelse i undersøgelsen.
  • En positiv laboratoriebekræftelse af corona virus sygdom 2019 (COVID-19) infektion eller højt klinisk indeks for mistanke om COVID-19.

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: Sekventiel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Cohort 1 Treatment Sequence (Seq) 1: GSK3494245 20 milligram (mg) fasted/Placebo (PBO)
Participants received 20 mg of GSK3494245 during dosing period 1 and Placebo matching the active dose amount during dosing period 2 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 1 Treatment Seq 2: PBO/GSK3494245 40mg fasted
Participants received Placebo during dosing period 1 and 40 mg of GSK3494245 during dosing period 2 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 1 Treatment Seq 3: GSK3494245 20mg fasted/GSK3494245 40mg fasted
Participants received 20 mg of GSK3494245 during dosing period 1 and 40 mg of GSK3494245 during dosing period 2 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Eksperimentel: Cohort 1 Treatment Seq 4: GSK3494245 20mg fasted/GSK3494245 40mg fasted
Participants received 20 mg of GSK3494245 during dosing period 1 and 40 mg of GSK3494245 during dosing period 2 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Eksperimentel: Cohort 2 Treatment Seq 1:GSK3494245 40mg fasted/GSK3494245 80mg fasted/GSK3494245 120mg fasted/PBO
Participants received 40 mg of GSK3494245 during dosing period 1, 80 mg of GSK3494245 during dosing period 2, 120 mg of GSK3494245 during dosing period 3 and matching Placebo during dosing period 4 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 2 Treatment Seq 2:GSK3494245 40mg fasted/GSK3494245 80mg fasted/PBO/GSK3494245 160mg fasted
Participants received 40 mg of GSK3494245 during dosing period 1, 80 mg of GSK3494245 during dosing period 2, matching placebo during dosing period 3 and 160 mg of GSK3494245 during dosing period 4 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 2 Treatment Seq 3:GSK3494245 40mg fasted/PBO/GSK3494245 120mg fasted/GSK3494245 160mg fasted
Participants received 40 mg of GSK3494245 during dosing period 1, matching placebo during dosing period 2, 120 mg of GSK3494245 during dosing period 3 and 160 mg of GSK3494245 during dosing period 4 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 2 Treatment Seq 4: PBO/GSK3494245 80mg fasted/GSK3494245 120mg fasted/GSK3494245 160mg fasted
Participants received placebo during dosing period 1, 80 mg of GSK3494245 during dosing period 2, 120 mg of GSK3494245 during dosing period 3 and 160 mg of GSK3494245 during dosing period 4 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 2A Treatment Seq 1: GSK3494245 150mg fasted
Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Eksperimentel: Cohort 2A Treatment Seq 2: GSK3494245 150mg fasted
Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Eksperimentel: Cohort 2A Treatment Seq 3: GSK3494245 150mg fasted
Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Eksperimentel: Cohort 2A Treatment Seq 4: PBO fasted
Participants received Placebo during dosing period 1 under fasted conditions, at Day 1.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 3 Treatment Seq 1: PBO fed/PBO fasted/GSK3494245 80mg fasted/GSK3494245 80mg fed
Participants received Placebo in fed conditions during dosing period 1, Placebo in fasted conditions during dosing period 2, 80 mg of GSK3494245 in fasted conditions during dosing period 3 and 80 mg of GSK3494245 in fed conditions during dosing period 4.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 3 Treatment Seq 2: PBO fasted/GSK3494245 80mg fed/PBO fed/GSK3494245 80mg fasted
Participants received Placebo in fasted conditions during dosing period 1, 80 mg of GSK3494245 in fed conditions during dosing period 2, placebo in fed conditions during dosing period 3 and 80 mg of GSK3494245 in fasted conditions during dosing period 4.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 3 Treatment Seq 3: GSK3494245 80mg fed/GSK3494245 80mg fasted/PBO fasted/PBO fed
Participants received 80 mg of GSK3494245 in fed conditions during dosing period 1, 80 mg of GSK3494245 in fasted conditions during dosing period 2, Placebo in fasted conditions during dosing period 3 and placebo in fed conditions during dosing period 4.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 3 Treatment Seq 4: GSK3494245 80mg fasted/PBO fed/GSK3494245 80mg fed/PBO fasted
Participants received 80 mg of GSK3494245 in fasted conditions during dosing period 1, Placebo in fed conditions during dosing period 2, 80 mg of GSK3494245 in fed conditions during dosing period 3 and placebo in fasted conditions during dosing period 4.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 3A Treatment Seq 1: PBO fed/GSK3494245 240mg fed
Participants received placebo in fed conditions during dosing period 1 and 240 mg of GSK3494245 in fed conditions during dosing period 2.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 3A Treatment Seq 2: GSK3494245 160mg fed/PBO fed
Participants received 160 mg of GSK3494245 in fed conditions during dosing period 1 and Placebo in fed conditions during dosing period 2.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Medicin: Placebo
Matching placebo capsules were provided
Eksperimentel: Cohort 3A Treatment Seq 3: GSK3494245 160mg fed/GSK3494245 240mg fed
Participants received 160 mg of GSK3494245 in fed conditions during dosing period 1 and 240 mg of GSK3494245 in fed conditions during dosing period 2.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Eksperimentel: Cohort 3A Treatment Seq 4: GSK3494245 160mg fed/GSK3494245 240mg fed
Participants received 160 mg of GSK3494245 in fed conditions during dosing period 1 and 240 mg of GSK3494245 in fed conditions during dosing period 2.
Medicin: GSK3494245
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of Participants With Adverse Events (AEs)
Tidsramme: From Day 1 (first dose) up to 14 days post last dose in each treatment period
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
From Day 1 (first dose) up to 14 days post last dose in each treatment period
Number of Participants With Serious Adverse Events (SAEs)
Tidsramme: From the signing of the informed consent form (a period starting up to 28 days before the first dose on Day 1) to up to 14 days after the last dose of each treatment period
A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
From the signing of the informed consent form (a period starting up to 28 days before the first dose on Day 1) to up to 14 days after the last dose of each treatment period
Number of Participants With Treatment Emergent AEs (TEAEs) and Treatment Emergent SAEs
Tidsramme: From Day 1 (first dose) up to 2 days post last dose in each treatment period

A TEAE and treatment emergent SAE is considered any untoward medical occurrence in a clinical study participant, considered by the investigator to have a causal relationship with study treatment.

A SAE is defined as any untoward medical occurrence that, at any dose: resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
From Day 1 (first dose) up to 2 days post last dose in each treatment period
Summary of Change From Baseline in Hematology Parameters: Basophils, Neutrophils, Eosinophils, Lymphocytes, Monocytes and Platelets
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the hematology parameters: basophils, neutrophils, eosinophils, lymphocytes, monocytes and platelets. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. Standard deviation (SD)=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Volume
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the hematology parameters: mean corpuscular volume. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the hematology parameters: mean corpuscular hemoglobin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Erythrocytes and Reticulocytes
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the hematology parameters: erythrocytes and reticulocytes. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Hemoglobin
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the hematology parameters: hemoglobin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Hematology Parameters: Hematocrit and Reticulocytes
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the hematology parameters: hematocrit and reticulocytes. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphate (ALP), Aspartate Aminotransferase (AST), Creatine Phosphokinase (CPK), and Gamma Glutamyl Transferase (GGT)
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the clinical chemistry parameters: ALT, ALP, AST, CPK, and GGT. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Clinical Chemistry Parameters: Albumin, Protein
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the clinical chemistry parameters: albumin and protein. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Clinical Chemistry Parameters: Bicarbonate, Calcium Corrected for Albumin, Glucose, Lactic Acid, Magnesium, Phosphate, Potassium, Sodium, Triglycerides, and Urea
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for clinical chemistry parameters: bicarbonate, calcium corrected for albumin, glucose, lactic acid, magnesium, phosphate, potassium, sodium, triglycerides, urea. Baseline was defined as the last non-missing pre-dose assessment for each cohort. Generally, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments on Day 1 lacked timing, the first recorded was used. If one Day 1 assessment lacked timing, the last available from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, Baseline was set to missing. Change from baseline is defined as post-dose value minus baseline value. SD=0.0000 indicates SD below the detectable assay limit, approximated to 0.0000.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the clinical chemistry parameters: bilirubin, creatinine, direct bilirubin. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Clinical Chemistry Parameters: C-reactive Protein (CRP)
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the clinical chemistry parameters: CRP. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Clinical Chemistry Parameters: pH
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Blood samples were collected for the assessment of the clinical chemistry parameters: pH. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.
At Day 2 and Day 4 in each treatment period compared to Baseline
Number of Participants With Worst-case Urinalysis Results
Tidsramme: From Day 1 up to 14 Days post last dose
Urine samples were collected for the assessment of urinalysis parameters, which include pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
From Day 1 up to 14 Days post last dose
Summary of Change From Baseline in Physical Examinations: Body Mass Index (BMI)
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Vital Signs: Respiratory Rate
Tidsramme: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Summary of Change From Baseline in Vital Signs: Supine Diastolic Blood Pressure, Supine Systolic Blood Pressure
Tidsramme: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Summary of Change From Baseline in Vital Signs: Supine Pulse Rate
Tidsramme: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Summary of Change From Baseline in Vital Signs: Tympanic Membrane Temperature
Tidsramme: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day 3 (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Summary of Change From Baseline in Physical Examinations: Weight
Tidsramme: At Day 2 and Day 4 in each treatment period compared to Baseline
Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value. SD=0.0000 is defined as SD resulted below the detectable limit of the assay and approximate to 0.0000.
At Day 2 and Day 4 in each treatment period compared to Baseline
Summary of Change From Baseline in Electrocardiogram (ECG) Parameters: Heart Rate
Tidsramme: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Triplicate 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.
At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Summary of Change From Baseline in ECG Parameters: PR Interval, QRS Interval, QT Interval, Corrected QT (QTc) Interval, QT Interval Corrected Using Bazett's Formula, QT Interval Corrected, Using Fridericia's Formula
Tidsramme: At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Triplicate 12-lead ECGs were obtained using an ECG machine that automatically measured the PR interval, QRS interval, QT interval, and QTc interval. Baseline was defined as the last non-missing pre-dose assessment for each cohort. In general, assessments on Study Day 1 taken before the first dose were used as Baseline. If multiple assessments were captured on Day 1 but the time of the first assessment was missing, the first recorded assessment was used. If only one Day 1 assessment lacked timing, the last available assessment from Day -1 or earlier was used. If no Day 1 assessments were available, the most recent data from Day -1 or screening was used. If all pre-dose data were missing, no derivation was performed, and Baseline was set to missing. Change from baseline value is defined as post-dose value minus baseline value.
At Day 1 (30 minutes, 1 hour [h], 1.5h, 2h, 2.5h, 4h, 8h, 12h), Day 2 (24h), Day (48h), and Day 4 in each treatment period compared to Baseline (pre-dose)
Number of Participants With Abnormal Cardiac Telemetry Findings
Tidsramme: Up to 24 hours post first dose on Day 1
Telemetry is defined as the continuous monitoring of a participant's heart rate and rhythm from a remote location.
Up to 24 hours post first dose on Day 1

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Area Under the Plasma Drug Concentration (AUC) Versus Time Curve (AUC[0-t]) of GSK3494245 Following Single Dose Administration, Under Fasting Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
AUC(0-t) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to the last measurable concentration.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
AUC (0-t) of GSK3494245 Following Single Dose Administration Under Fed Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
AUC(0-t) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to the last measurable concentration.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
AUC-time Curve From Time Zero to Extrapolated to Infinity (AUC[0-inf]) of GSK3494245 Following Single Dose Administration Under Fasting Condition
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
AUC(0-inf) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to infinity.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
AUC (0-inf) of GSK3494245 Following Single Dose Administration Under Fed Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
AUC(0-inf) was calculated by using a standard non-compartmental analysis and was defined as area under the curve from time 0 to infinity
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Maximum Observed Plasma Drug Concentration (Cmax) of GSK3494245 Following Single Dose Administration Under Fasting Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Cmax is defined as the maximum concentration of the drug in plasma.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Cmax of GSK3494245 Following Single Dose Administration Under Fed Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Cmax is defined as the maximum concentration of the drug in plasma.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Time to Maximum Observed Plasma Drug Concentration (Tmax) of GSK3494245 Following Single Dose Administration Under Fasting Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Tmax is defined as a measure of the time required to reach the maximum concentration of the drug.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Tmax of GSK3494245 Following Single Dose Administration Under Fed Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Tmax is defined as a measure of the time required to reach the maximum concentration of the drug.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Apparent Terminal Half-life (t1/2) of GSK3494245 Following Single Dose Administration Under Fasting Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
t1/2 is defined as the time required by the plasma concentration to decline by 50%.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
t1/2 of GSK3494245 Following Single Dose Administration Under Fed Conditions
Tidsramme: At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
t1/2 is defined as the time required by the plasma concentration to decline by 50%.
At Day 1 (post-dose) in each treatment period (1, 2, 3, and 4)
Dose-proportionality Assessment Using AUC(0-inf) Following a Single Dose of GSK3494245
Tidsramme: At Day 1 (post-dose)
A power model was used to assess the dose proportionality. A slope of 1 indicates that PK increased linearly with the dose. A slope greater than 1 indicates that PK increased more than proportionally with increase in the dose.
At Day 1 (post-dose)
Dose-proportionality Assessment Using Cmax Following Single Dose of GSK3494245
Tidsramme: At Day 1 (post-dose)
A power model was used to assess the dose proportionality. A slope of 1 indicates that PK increased linearly with the dose. A slope greater than 1 indicates that PK increased more than proportionally with increase in the dose.
At Day 1 (post-dose)

Samarbejdspartnere og efterforskere

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

Sponsor

GlaxoSmithKline

Efterforskere

  • Studieleder: GSK Clinical Trials, GlaxoSmithKline

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)

29. september 2020

Primær færdiggørelse (Faktiske)

14. januar 2024

Studieafslutning (Faktiske)

14. januar 2024

Datoer for studieregistrering

Først indsendt

5. august 2020

Først indsendt, der opfyldte QC-kriterier

5. august 2020

Først opslået (Faktiske)

7. august 2020

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

1. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

8. april 2026

Sidst verificeret

1. april 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 208441
  • 2019-004492-39 (EudraCT nummer)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

IPD for denne undersøgelse vil blive gjort tilgængelig via webstedet for anmodning om kliniske undersøgelsesdata.

IPD-delingstidsramme

IPD vil blive gjort tilgængelig inden for 6 måneder efter offentliggørelsen af ​​resultaterne af undersøgelsens primære endepunkter, vigtige sekundære endepunkter og sikkerhedsdata.

IPD-delingsadgangskriterier

Adgang gives, efter at et forskningsforslag er indsendt og har modtaget godkendelse fra det uafhængige evalueringspanel, og efter en datadelingsaftale er på plads. Adgangen gives i en indledende periode på 12 måneder, men en forlængelse kan gives, når det er berettiget, i op til yderligere 12 måneder.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

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