Säkerhet, tolerabilitet och farmakokinetik (PK) undersökning av GSK3494245 hos friska deltagare
8 april 2026 uppdaterad av: GlaxoSmithKline
En randomiserad, dubbelblind, placebokontrollerad, första gången i mänsklig studie för att utvärdera säkerheten, tolerabiliteten och farmakokinetiken för enstaka (i både matade och fasta stater) doser av GSK3494245 hos friska deltagare
Detta är en fas 1, dubbelblind, randomiserad, placebokontrollerad, första gången i human (FTIH) studie för att bedöma säkerheten, tolerabiliteten och PK för en engångsdos av GSK3494245.
Studien kommer att bestå av 3 kohorter, genomförda i ett sekventiellt sätt.
Kohorter 1 och 2 kommer att bestå av en enkel stigande dos (SAD), crossover-design där varje deltagare kommer att få maximalt 3 stigande orala doser av GSK3494245 och 1 placebodos under fasta.
Vid varje dosnivå kommer GSK3494245 och placebo att administreras i ett 3:1-förhållande, inom varje period, enligt randomiseringsschemat på ett blindat sätt.
Kohort 3 kommer att bestå av en 2-vägs crossover som inkluderar 1 doseringskur under fasta och sedan matade förhållanden och 1 regim under förhållanden med mat och sedan fasta i förhållandet 1:1.
De utfodrade förhållandena kommer att undersöka effekten av säkerhet, tolerabilitet och PK av en enstaka dos av GSK3494245 efter matadministrering.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
59
Fas
- Fas 1
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Cambridge, Storbritannien, CB2 2GG
- GSK Investigational Site
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 50 år (Vuxen)
Tar emot friska volontärer
Ja
Beskrivning
Inklusionskriterier
- Deltagaren måste vara 18 till <=50 år, vid tidpunkten för undertecknandet av det informerade samtycket.
- Deltagaren måste vara frisk enligt utredaren eller medicinskt kvalificerad representant baserat på en medicinsk utvärdering inklusive medicinsk historia, fysisk undersökning, laboratorietester och hjärtövervakning. En deltagare med en klinisk abnormitet eller laboratorieparametrar som inte är specifikt listade i inklusions- eller uteslutningskriterierna, utanför det normala referensintervallet för populationen som studeras får inkluderas endast om utredaren i samråd med medicinsk monitor ( vid behov) samtycka till och dokumentera att fyndet sannolikt inte kommer att introducera ytterligare riskfaktorer och inte kommer att störa studieprocedurerna.
- Kroppsvikt >=50 kilogram (kg) och body mass index (BMI) inom intervallet 18,5-28 kilogram per kvadratmeter kvadrat (kg/m^2) (inklusive).
- Endast manliga deltagare. En manlig deltagare med en kvinnlig partner med reproduktionspotential måste gå med på att använda preventivmedel under interventionsperioden och i minst 90 dagar efter den sista dosen av studiebehandlingen och avstå från att donera spermier under denna period.
- Kan ge undertecknat informerat samtycke, vilket inkluderar efterlevnad av kraven och begränsningarna som anges i formuläret för informerat samtycke (ICF) och protokollet.
Exklusions kriterier
- Historik eller förekomst av kardiovaskulära, respiratoriska, lever-, njur-, gastrointestinala, endokrina, hematologiska eller neurologiska störningar som avsevärt kan förändra absorption, metabolism eller eliminering av läkemedel; utgör en risk när man tar studiebehandlingen; eller stör tolkningen av data.
- Onormalt blodtryck, som fastställts av utredaren.
- Tidigare historia av leishmaniasis.
- Alaninaminotransferas (ALT) större än 1,5 gånger övre normalgräns (ULN).
- Totalt bilirubin högre än 1,5 gånger ULN (isolerat bilirubin högre än 1,5 gånger ULN är acceptabelt om totalt bilirubin fraktioneras och direkt bilirubin mindre än 35 procent [%]).
- Aktuell eller kronisk historia av leversjukdom, eller kända lever- eller gallavvikelser (med undantag för Gilberts syndrom eller asymtomatiska gallstenar).
- Aktuell eller historia av kliniskt signifikant gastrit eller gastroduodenala sår eller regelbunden användning av icke-steroida antiinflammatoriska läkemedel (NSAID).
- Konsumtion av mer än 14 enheter/vecka alkohol (manliga frivilliga).
- Aktuell eller historia av förändring i smak eller lukt utan någon rimlig klinisk förklaring baserad på utredarens kliniska bedömning.
- QTc större än 450 millisekunder (ms) baserat på genomsnittet av triplikat EKG.
- Vågformsavvikelser inklusive prematur ventrikulär kontraktion (PVC) tripletter och mer än 500 enstaka PVC under 24 timmar, eller andra abnormiteter enligt utredarens bedömning.
- Medicinsk historia av hjärtarytmier eller hjärtsjukdom eller en familje- eller personlig historia av långt QT-syndrom.
- Tidigare eller avsedd användning av receptfria eller receptbelagda läkemedel, inklusive växtbaserade läkemedel, NSAID, protonpumpshämmare (PPI) eller antihistamin 2 receptor (H2) antagonister inom 7 dagar (eller 14 dagar om läkemedlet är ett potentiellt enzym inducerare) eller 5 halveringstider (beroende på vilket som är längst) före dosering. Annan samtidig medicinering kan övervägas från fall till fall av utredaren i samråd med medicinsk monitor. Paracetamol är tillåtet (högst <=2 gram/dag).
- Deltagande i studien som skulle resultera i förlust av blod eller blodprodukter på över 500 milliliter (mL) inom en 56-dagarsperiod.
- Exponering för mer än 4 nya kemiska enheter inom 12 månader före den första doseringsdagen.
- Nuvarande registrering eller tidigare deltagande inom de senaste 30 dagarna före undertecknande av samtycke i någon annan klinisk studie som involverar en undersökningsstudieintervention eller någon annan typ av medicinsk forskning.
- Nuvarande registrering eller tidigare deltagande i denna kliniska studie.
- Deltagare med njurfunktion definierad som Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) med en åldersanpassad glomerulär filtrationshastighet (GFR) <90 (milliliter per minut per 1,73 kvadratmeter [mL/min/1,73m^2]).
- Screening av urinalbumin:kreatininförhållande >30 milligram per gram (mg/g) (>3 milligram per millimol [mg/mmol])
- Förekomst av testresultat för hepatit B-ytantigen (HBsAg) vid screening.
- Positivt testresultat för hepatit C-antikropp vid screening.
- Positivt testresultat för hepatit C-ribonukleinsyra (RNA) vid screening.
- Positivt antikroppstest för humant immunbristvirus (HIV).
- Förekomst av kliniskt signifikant hematuri och/eller proteinuri.
- Kolmonoxidnivåer som tyder på rökning eller historia eller regelbunden användning av tobak eller nikotinhaltiga produkter inom 3 månader före screening.
- Positiv drog/alkoholskärm före studien.
- Regelbunden användning av kända droger.
- Endast Food Effect Cohort 3: Deltagare får inte ha några dietrestriktioner (t.ex. laktosintolerans) eller oförmåga att äta gelatin eller en anpassad standardmåltid (inkluderar 35-40 % fetthalt).
- Mateffekt endast kohort 3: Historik av gallblåsoperationer eller avlägsnande av gallblåsan, eller historia av ett akut sjukdomstillstånd (t.ex. kolelithiasis) inom 14 dagar före mottagandet av studiebehandlingen.
- Deltagarna får inte ha rest till ett område (som bestämts av utredaren) med en hög förekomst av leishmaniala/parasitära infektioner under de 6 månaderna före screening eller avser att göra det under de 3 månaderna efter den sista dosen av studiebehandlingen.
- Känslighet för någon av studiebehandlingarna, eller komponenter därav, eller läkemedel eller annan allergi som, enligt utredarens eller GSK Medical Monitors åsikt, kontraindikerar deltagande i studien.
- En positiv laboratoriebekräftelse på infektion med coronavirussjukdom 2019 (COVID-19), eller högt kliniskt index för misstanke om covid-19.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Sekventiell tilldelning
- Maskning: Dubbel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
|
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
|
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
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Experimentell: Cohort 2A Treatment Seq 1: GSK3494245 150mg fasted
Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
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Experimentell: Cohort 2A Treatment Seq 2: GSK3494245 150mg fasted
Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
|
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Experimentell: Cohort 2A Treatment Seq 3: GSK3494245 150mg fasted
Participants received 150 mg of GSK3494245 during dosing period 1 under fasted conditions, at Day 1.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
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Experimentell: Cohort 2A Treatment Seq 4: PBO fasted
Participants received Placebo during dosing period 1 under fasted conditions, at Day 1.
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Matching placebo capsules were provided
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
|
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
|
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Experimentell: 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.
|
Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
|
|
Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
|
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
|
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
Matching placebo capsules were provided
|
|
Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
|
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Experimentell: 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.
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Capsule of 10-250 mg dose strength were provided in labelled High Density Polyethylene (HDPE) bottles.
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Number of Participants With Adverse Events (AEs)
Tidsram: From Day 1 (first dose) up to 14 days post last dose in each treatment period
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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.
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From Day 1 (first dose) up to 14 days post last dose in each treatment period
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Number of Participants With Serious Adverse Events (SAEs)
Tidsram: 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
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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.
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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
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Number of Participants With Treatment Emergent AEs (TEAEs) and Treatment Emergent SAEs
Tidsram: From Day 1 (first dose) up to 2 days post last dose in each treatment period
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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
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Summary of Change From Baseline in Hematology Parameters: Basophils, Neutrophils, Eosinophils, Lymphocytes, Monocytes and Platelets
Tidsram: 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.
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At Day 2 and Day 4 in each treatment period compared to Baseline
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Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Volume
Tidsram: 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.
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At Day 2 and Day 4 in each treatment period compared to Baseline
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Summary of Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin
Tidsram: 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
|
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Summary of Change From Baseline in Hematology Parameters: Erythrocytes and Reticulocytes
Tidsram: 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
|
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Summary of Change From Baseline in Hematology Parameters: Hemoglobin
Tidsram: 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
|
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Summary of Change From Baseline in Hematology Parameters: Hematocrit and Reticulocytes
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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)
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Area Under the Plasma Drug Concentration (AUC) Versus Time Curve (AUC[0-t]) of GSK3494245 Following Single Dose Administration, Under Fasting Conditions
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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)
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Studierektor: GSK Clinical Trials, GlaxoSmithKline
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
29 september 2020
Primärt slutförande (Faktisk)
14 januari 2024
Avslutad studie (Faktisk)
14 januari 2024
Studieregistreringsdatum
Först inskickad
5 augusti 2020
Först inskickad som uppfyllde QC-kriterierna
5 augusti 2020
Första postat (Faktisk)
7 augusti 2020
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
1 maj 2026
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
8 april 2026
Senast verifierad
1 april 2026
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 208441
- 2019-004492-39 (EudraCT-nummer)
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
JA
IPD-planbeskrivning
IPD för denna studie kommer att göras tillgänglig via webbplatsen för begäran om kliniska studier.
Tidsram för IPD-delning
IPD kommer att göras tillgänglig inom 6 månader efter publicering av resultaten av de primära endpoints, viktiga sekundära endpoints och säkerhetsdata för studien.
Kriterier för IPD Sharing Access
Åtkomst ges efter att ett forskningsförslag har lämnats in och har fått godkännande från den oberoende granskningspanelen och efter att ett datadelningsavtal har ingåtts.
Tillträde ges för en inledande period av 12 månader men en förlängning kan beviljas, när det är motiverat, med upp till ytterligare 12 månader.
IPD-delning som stöder informationstyp
- STUDY_PROTOCOL
- SAV
- ICF
- CSR
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Nej
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
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