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Evaluering av farmakokinetikken, sikkerheten og tolerabiliteten til delamanid i kombinasjon med optimalisert multilegemiddelbakgrunnsregime (OBR) for multiresistent tuberkulose (MDR-TB) hos HIV-infiserte og HIV-uinfiserte barn med MDR-TB

31. mai 2026 oppdatert av: National Institute of Allergy and Infectious Diseases (NIAID)

En fase I/II åpen, enkeltarmsstudie for å evaluere farmakokinetikken, sikkerheten og toleransen til Delamanid i kombinasjon med optimalisert multimedikamentbakgrunnsregime (OBR) for multiresistent tuberkulose (MDR-TB) hos HIV-infiserte og HIV -Uinfiserte barn med MDR-TB

Denne studien vil evaluere farmakokinetikken, sikkerheten og tolerabiliteten til anti-tuberkulose (TB) medikamentet delamanid (DLM) i kombinasjon med et optimert multidrug bakgrunnsregime (OBR) for multidrug-resistent tuberkulose (MDR-TB) hos HIV-infiserte og HIV-uinfiserte barn med MDR-TB.

Studieoversikt

Status

Fullført

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

Formålet med denne studien er å evaluere farmakokinetikken, sikkerheten og toleransen til anti-TB-medikamentet DLM i kombinasjon med OBR for MDR-TB hos HIV-infiserte og HIV-uinfiserte barn med MDR-TB.

Deltakerne vil bli registrert i en av fire alderskull: 12 til under 18 år, 6 til under 12 år, 3 til mindre enn 6 år, eller 0 til under 3 år. Alle deltakere vil få DLM dosert i henhold til aldersgruppe og vekt i 24 uker.

Studiebesøk vil finne sted ved studiestart; Uke 2 og 4; hver 4. uke gjennom uke 40; og i uke 48, 60, 72 og 96. Besøk kan omfatte fysiske undersøkelser; samling av blod, urin og oppspytt; røntgen av brystet; elektrokardiogrammer (EKG); hørselsprøver; etterlevelsesvurderinger; og akseptabilitetsspørreskjemaer.

Studietype

Intervensjonell

Registrering (Faktiske)

37

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • India
    • Maharashtra
      • Pune, Maharashtra, India, 411001
        • Byramjee Jeejeebhoy Medical College (BJMC) CRS
  • Sør-Afrika
    • Gauteng
      • Johannesburg, Gauteng, Sør-Afrika
        • Sizwe CRS
    • North West
      • Klerksdorp, North West, Sør-Afrika, 2574
        • PHRU Matlosana CRS
    • Western Cape
      • Cape Town, Western Cape, Sør-Afrika, 7505
        • Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS
  • Tanzania
      • Moshi, Tanzania
        • Kilimanjaro Christian Medical Centre (KCMC)

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

Ikke eldre enn 14 år (Barn)

Tar imot friske frivillige

Nei

Beskrivelse

Inklusjonskriterier:

  • Foreldre (eller verge) er villig og i stand til å gi skriftlig informert samtykke for deltakelse i barns studie. I tillegg, for barn hvis samtykke kreves i henhold til retningslinjene og prosedyrene for nettstedets institusjonelle vurderingsstyre/etiske komité (IRB/EC), er barnet villig og i stand til å gi skriftlig samtykke for studiedeltakelse.
  • Alder under 18 år ved innmelding
  • HIV-uinfisert eller HIV-infisert (se protokollen for mer informasjon om dette kriteriet)
  • Hvis HIV-infisert: Startet standardbehandlingen antiretroviral terapi (ART) minst to uker før registrering (merk: regimer inkludert efavirenz [EFV], nevirapin [NVP], en boostet proteasehemmer [PI] eller integrert trådoverføring inhibitor [INSTI] er tillatt)

  • Bekreftet eller sannsynlig MDR-TB klassifisert som følger:

    • Bekreftet MDR-TB (eller rifampicin mono-resistent TB [RMR-TB], pre-extensivt drug-resistent [XDR] eller XDR-TB):

      • Intra-thorax (pulmonal) TB basert på røntgen av thorax forenlig med TB, og/eller noen av følgende former for ekstrathorakal TB:
      • 1) Perifer TB-lymfadenitt
      • 2) Pleural effusjon eller fibrotiske pleuralesjoner
      • 3) Trinn 1 TB meningitt
      • 4) Miliær og abdominal tuberkulose
      • 5) Andre ikke-utbredte former for tuberkulosesykdom (se også eksklusjonskriterium nedenfor)
      • OG
      • Mikrobiologisk bekreftelse av Mycobacterium tuberculosis fra alle kliniske prøver ved enten kultur eller molekylære metoder (inkludert Xpert MTB/RIF)
      • OG
      • Legemiddelresistens demonstrert ved genotypiske (molekylære) eller fenotypiske metoder, med ett av følgende resistensmønstre:
      • MDR-TB (resistens mot både rifampicin og isoniazid)
      • RMR-TB eller der ytterligere isoniazid (INH) resistens ikke er bekreftet (dvs. isolert Xpert MTB/RIF rifampicinresistens)
      • Pre-XDR-TB (MDR-TB pluss motstand mot enten et fluorokinolon eller et andrelinjes injiserbart middel)
      • XDR-TB (MDR-TB pluss motstand mot både en fluorokinolon og en andrelinje injiserbar)
      • Merk: RMR-TB, MDR-TB, pre-XDR-TB og XDR-TB blir derfor samlet referert til som "MDR-TB" for formålet med protokollen

    • Sannsynlig MDR-TB (eller RMR, pre-XDR eller XDR-TB), med inkludering av intrathorakal og/eller ekstrathorakal TB som listet nedenfor:

      • En presumptiv diagnose av intratorakal (pulmonal) tuberkulose basert på veldokumenterte kliniske symptomer eller tegn på tuberkulose OG røntgen av thorax forenlig med tuberkulose, og/eller noen av følgende former for ekstratorakal tuberkulose:
      • Perifer TB-lymfadenitt
      • Pleural effusjon eller fibrotiske pleuralesjoner
      • Trinn 1 TB meningitt
      • Miliær og abdominal tuberkulose,
      • Andre ikke-utbredte former for TB-sykdom (se også eksklusjonskriterium nedenfor)
      • OG
      • En av følgende:
      • Eksponering for et bekreftet MDR-TB-kildetilfelle* (RMR-TB, pre-XDR-TB, XDR-TB)
      • Dokumentert manglende respons på et førstelinjeregime, og hvor overholdelse var godt dokumentert.
      • OG
      • Den kliniske beslutningen er tatt for å behandle for MDR-TB
      • * Bekreftede MDR-TB-kildetilfeller definert som et tilfelle med intratorakal tuberkulose med eller uten ekstratorakal tuberkulose, med mikrobiologisk bekreftelse av Mycobacterium tuberculosis fra alle kliniske prøver ved enten kultur eller molekylære metoder (inkludert Xpert MTB/RIF), og med påvist medikamentresistens ved genotypiske (molekylære) eller fenotypiske metoder, med hvilket som helst av resistensmønstrene beskrevet ovenfor.
  • Albuminnivå større enn 2,8 g/dL innen 30 dager før registrering
  • Kalium større enn 3,4 og mindre enn 5,6 mmol/L; magnesium større enn 0,59 mmol/L innen 30 dager før påmelding. Merk: Elektrolytter kan fylles på og en ny kontroll kan utføres for å oppfylle kvalifikasjonskriteriene.
  • BMI Z-score større enn -3 for barn eldre enn eller lik 5 år; vekt for lengde/høyde Z-score større enn -3 for barn under 5 år (ved bruk av siste World Health Organization-score), ved screening
  • Vekt større enn eller lik 3 kg, ved screening
  • Har satt i gang et passende optimert bakgrunnsregime (OBR) MDR-TB-behandlingsregime i henhold til rutinemessig behandlingsavgjørelse, minst to uker, men ikke mer enn åtte uker før påmelding, og etter stedsforskerens oppfatning, tolererer regimet godt kl. registrering. Merk: Et passende OBR MDR-TB-behandlingsregime er definert som å inkludere komponenter basert på sensitiviteten til det infiserte isolatet, hvis kjent, og tidligere behandlingshistorie, hvis kjent. Dette regimet bør også følge OBR MBR-TB-behandlingsretningslinjene som beskrevet i protokollen.
  • Hvis mann og deltar i seksuell aktivitet som kan føre til graviditet for den kvinnelige partneren: godtar å bruke en barrieremetode for prevensjon (dvs. mannlig kondom) gjennom de første 28 ukene på studien (dvs. inntil fire uker etter seponering av DLM).
  • Hvis kvinne og reproduktivt potensial, definert som å ha nådd menarche og ikke ha gjennomgått en dokumentert steriliseringsprosedyre (hysterektomi, bilateral ooforektomi eller salpingektomi): Negativ graviditetstest ved screening innen 14 dager før innmelding.
  • Hvis kvinne, med reproduktivt potensial (som definert i protokollen), og deltar i seksuell aktivitet som kan føre til graviditet: samtykker i å unngå graviditet og å bruke en av følgende former for prevensjon mens du mottar DLM og i en måned etter avsluttet DLM : kondomer, diafragma eller livmorhalshette, intrauterin enhet (IUD), hormonbasert prevensjon. Den valgte metoden må startes før påmelding.

Ekskluderingskriterier:

  • Kjent allergi mot eventuelle nitroimidazoler eller nitroimidazolderivater
  • Aktiv bruk av forbudte medisiner oppført i protokollen, innen 3 dager etter påmelding

  • Deltakeren har en historikk med noe av følgende, som bestemt av stedets etterforsker eller utpekt basert på mors rapport og tilgjengelige medisinske journaler:

    • En betydelig hjertearytmi som krever medisinering eller en historie med hjertesykdom (hjertesvikt, koronararteriesykdom) som øker risikoen for Torsade de Pointes
    • Betydelig gastrointestinal (GI), metabolsk, nevropsykiatrisk, nyre- eller endokrin sykdom ved screening som etter etterforskerens mening vil utelukke sikker deltakelse i utprøvingen og/eller vurderingen av primære endepunkter
    • Tidligere eksponering for DLM eller pretomanid
    • Merk: Deltakere kan ha mottatt opptil 14 + 3 dager (dvs. opptil 17 dager) med DLM før påmelding
  • Unormalt elektrokardiogram (EKG) (inkludert QTcF [middelverdi av QT-intervall, korrigert med Fredericia-korreksjon, på EKG utført i tre eksemplarer] større enn eller lik 450 ms, atrioventrikulær blokkering eller forlenget QRS større enn eller lik 120 ms) ved screening
  • Karnofsky scorer mindre enn 30 % for deltakere over eller lik 16 år eller Lansky play-score mindre enn 30 % for deltakere under 16 år, ved screening
  • Alkoholinntak som etter studieforskerens oppfatning potensielt kan forstyrre studiedeltakelsen og/eller introdusere sikkerhetsproblemer ved bruk av DLM
  • Ammende med planer om å amme, ved påmelding
  • Tuberkuløs meningitt (TBM) trinn 2 eller 3, eller osteoartikulær TB ved screening
  • Samregistrert i alle andre studier som involverer farmakologiske regimer, ved screening
  • Ved HIV-eksponert og under 2 år: Amming ved påmelding

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomisert
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Cohort 1 (>=12 to < 18 years)
Participants received delamanid (DLM) twice daily for 24 weeks. Participants also received non-study prescribed OBR for MDR-TB.
Legemiddel: Delamanid

Administered orally; dosing based on participants' weight.

≥ 40 kg: 100 mg twice daily (adult formulation); 30 to < 40 kg: 50 mg twice daily (adult formulation); 15 to < 30 kg: 25 mg twice daily (pediatric formulation); < 15 kg: 15 mg twice daily (pediatric formulation)

Andre navn:
  • DLM
Legemiddel: Optimized multidrug background regimen (OBR) for children with MDR-TB
Non-study prescribed OBR varied according to local, national, and/or international guidelines for treatment of children with MDR-TB. Administered in addition to DLM for 24 weeks.
Eksperimentell: Cohort 2 (>=6 to < 12 years)
Participants received delamanid (DLM) twice daily for 24 weeks. Participants also received non-study prescribed OBR for MDR-TB.
Legemiddel: Delamanid

Administered orally; dosing based on participants' weight.

≥ 40 kg: 100 mg twice daily (adult formulation); 30 to < 40 kg: 50 mg twice daily (adult formulation); 15 to < 30 kg: 25 mg twice daily (pediatric formulation); < 15 kg: 15 mg twice daily (pediatric formulation)

Andre navn:
  • DLM
Legemiddel: Optimized multidrug background regimen (OBR) for children with MDR-TB
Non-study prescribed OBR varied according to local, national, and/or international guidelines for treatment of children with MDR-TB. Administered in addition to DLM for 24 weeks.
Eksperimentell: Cohort 3 (>=3 to < 6 years)
Participants received delamanid (DLM) twice daily for 24 weeks. Participants also received non-study prescribed OBR for MDR-TB.
Legemiddel: Delamanid

Administered orally; dosing based on participants' weight.

≥ 40 kg: 100 mg twice daily (adult formulation); 30 to < 40 kg: 50 mg twice daily (adult formulation); 15 to < 30 kg: 25 mg twice daily (pediatric formulation); < 15 kg: 15 mg twice daily (pediatric formulation)

Andre navn:
  • DLM
Legemiddel: Optimized multidrug background regimen (OBR) for children with MDR-TB
Non-study prescribed OBR varied according to local, national, and/or international guidelines for treatment of children with MDR-TB. Administered in addition to DLM for 24 weeks.
Eksperimentell: Cohort 4 (>=0 to < 3 years)
Participants received delamanid (DLM) twice daily for 24 weeks. Participants also received non-study prescribed OBR for MDR-TB.
Legemiddel: Delamanid

Administered orally; dosing based on participants' weight.

≥ 40 kg: 100 mg twice daily (adult formulation); 30 to < 40 kg: 50 mg twice daily (adult formulation); 15 to < 30 kg: 25 mg twice daily (pediatric formulation); < 15 kg: 15 mg twice daily (pediatric formulation)

Andre navn:
  • DLM
Legemiddel: Optimized multidrug background regimen (OBR) for children with MDR-TB
Non-study prescribed OBR varied according to local, national, and/or international guidelines for treatment of children with MDR-TB. Administered in addition to DLM for 24 weeks.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Participants With Adverse Events of ≥ Grade 3 Severity
Tidsramme: Measured from entry through Week 24
At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). 95% CIconfidence interval (CI) computed using exact Clopper-Pearson method.
Measured from entry through Week 24
Percentage of Participants With Adverse Events of ≥ Grade 3 Assessed by the Core Team to be at Least Possibly Related to the Study Drug
Tidsramme: Measured from entry through Week 24
At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). 95% CI computed using exact Clopper-Pearson method.
Measured from entry through Week 24
Percentage of Participants Who Were Terminated From Study Treatment Due to a Drug-related Adverse Event
Tidsramme: Measured from entry through Week 24
At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1. 95% CI computed using exact Clopper-Pearson method.
Measured from entry through Week 24
Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec
Tidsramme: Entry, weeks 2, 8, 12, 16, 20, and 24
Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits were performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were counted if they had QTcF ≥ 500 msec at any study visit from entry to Week 24. 95% CI computed using exact Clopper-Pearson method.
Entry, weeks 2, 8, 12, 16, 20, and 24
Percentage of Participants Who Died Through Week 24
Tidsramme: Measured from entry through Week 24
Death due to all causes included. 95% CI computed using exact Clopper-Pearson method.
Measured from entry through Week 24
Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h) DLM
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose

PK parameter was determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model

The starting population PK model was developed on data from Otsuka study 232 and 233 (1). NONMEM was used when developing the final model for the population in this study.

  • Developed a population PK model as part of the final PK analysis
  • Data used in the population PK analysis included the semi-intensive PK visit (week 0, 2 and 8) and sparse PK visits (week 4, 12, 16, 24 and 28).
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Geometric Mean of Area Under the Concentration Versus Time Curve (AUC0-24h) DM-6705
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose

PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model

The starting population PK model was developed on data from Otsuka study 232 and 233 (1). NONMEM was used when developing the final model for the population in this study.

  • Developed a population PK model as part of the final PK analysis
  • Data used in the population PK analysis included the semi-intensive PK visit (week 0, 2 and 8) and sparse PK visits (week 4, 12, 16, 24 and 28).
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Geometric Mean of Area of Maximal Concentration (Cmax) DLM
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Geometric Mean of Area of Maximal Concentration (Cmax) DM-6705
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Time of Maximal Concentration (Tmax) DLM
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Time of Maximal Concentration (Tmax) DM-6705
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Oral Clearance (Cl/F) DLM
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Oral Clearance (Cl/F) DM-6705
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Volume of Distribution (Vd) DLM
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Volume of Distribution (Vd) DM-6705
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Mean Absorption Time (MAT) DLM
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Terminal Half-life (t1/2) DLM
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
Median Terminal Half-life (t1/2) DM-6705
Tidsramme: Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose
PK parameter determined from plasma concentration-time profiles, dosing information and participant covariates using the final population PK model
Approximately day 10 (Week 2) at pre-dose, and 2, 4, and hours post dose

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Participants With Adverse Events ≥ Grade 3 Severity
Tidsramme: Measured from entry through Week 72 post DLM
At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. 95% CI computed using exact Clopper-Pearson method.
Measured from entry through Week 72 post DLM
Percentage of Participants With Adverse Events ≥ Grade 3 Severity Assessed by the Core Team to be at Least Possibly Related to the Study Drug
Tidsramme: Measured from entry through Week 72 post DLM
At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. 95% CI computed using exact Clopper-Pearson method.
Measured from entry through Week 72 post DLM
Percentage of Participants With Absolute Corrected QT Interval by Fridericia (QTcF) ≥ 500 Msec
Tidsramme: Screening, Entry, weeks 2, 8, 12, 16, 20, 24 and week 28
Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits should be performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were counted as having an outcome if they had QTcF ≥ 500 msec at any study visit from entry to Week 28. 95% CI computed using exact Clopper-Pearson method.
Screening, Entry, weeks 2, 8, 12, 16, 20, 24 and week 28
Percentage of Participants Who Died Through Week 72 Post DLM
Tidsramme: Measured from entry through Week 72 post DLM
Death due to all causes included. 95% CI computed using exact Clopper-Pearson method.
Measured from entry through Week 72 post DLM
Percentage of Participants With Adverse Events ≥ Grade 2 Severity
Tidsramme: Measured from entry through Week 72 post DLM
At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. 95% CI computed using exact Clopper-Pearson method.
Measured from entry through Week 72 post DLM
Percentage of Participants With Adverse Events ≥ Grade 2 Severity Assessed by the Core Team to be at Least Possibly Related to the Study Drug.
Tidsramme: Measured from entry through Week 72 post DLM
At entry and follow-up, all lab results, signs and symptoms, and diagnoses were recorded. The core team reviewed and confirmed the sites assessment of event relatedness to study drug. An adverse event (AE) is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4= potentially life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1). A higher grade indicates worse outcome. 95% CI computed using exact Clopper-Pearson method.
Measured from entry through Week 72 post DLM
Count of Participants With Change in QTcF Interval From Baseline of Greater Than 60 ms
Tidsramme: Entry, weeks 2, 8, 12, 16, 20, 24, and week 28
Evaluation of the Electrocardiogram (ECG) QTcF was performed per protocol. ECGs conducted at these visits should be performed in triplicate (if possible). Consultation with the protocol cardiologist was available and encouraged for any abnormal or equivocal ECG findings and/or questions related to cardiac toxicities and assessment. Participants were counted if they had QTcF was greater than 60 msec at any study visit from entry to Week 28.
Entry, weeks 2, 8, 12, 16, 20, 24, and week 28
Percentage of Participants (Overall) With TB Treatment Outcomes
Tidsramme: Measured from entry through Week 72 post DLM
Site investigator assessment of participant TB treatment outcomes through last study visit were entered into the eCRF. Treatment outcomes in children were defined as bacteriologic cure, probable cure, death, treatment failure, TB recurrence, and loss to follow-up as per protocol.
Measured from entry through Week 72 post DLM
Number of Participants Who Had Permanently Discontinued Study Drug Whilst on Study Due to Intolerance or Refusal to Take Medication
Tidsramme: Measured from entry through Week 24
Participants were assessed for tolerability of the study drug during the study by their intolerance or refusal to take the medications
Measured from entry through Week 24
Frequency of Cumulative Responses to Taste of Study Drug in an Acceptability Assessment
Tidsramme: Assessments conducted at weeks 2, 8 and 24
Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. The participants had the option of taking the study drug either as dispersible tablet or tablet formulation.
Assessments conducted at weeks 2, 8 and 24
Frequency of Cumulative Responses to Formulation of Study Drug in an Acceptability Assessment
Tidsramme: Assessments conducted at weeks 2, 8 and 24
Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. The participants had the option of taking the study drug either as dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation.
Assessments conducted at weeks 2, 8 and 24
Frequency of Cumulative Responses to Taste of Dispersible Tablet Doses in an Acceptability Assessment
Tidsramme: Assessments conducted at weeks 2, 8 and 24
Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. Participants' dose formulations were not restrictive as at each visit, the participant was given the option of taking the study drug as either a dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation.
Assessments conducted at weeks 2, 8 and 24
Frequency of Cumulative Responses to Administration of Dispersible Tablet Doses in an Acceptability Assessment
Tidsramme: Assessments conducted at weeks 2, 8 and 24
Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. Participants' dose formulations were not restrictive as at each visit, the participant was given the option of taking the study drug as either a dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation.
Assessments conducted at weeks 2, 8 and 24
Frequency of Cumulative Responses to Taste of Tablet Doses in an Acceptability Assessment
Tidsramme: Assessments conducted at weeks 2, 8 and 24
Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. Participants' dose formulations were not restrictive as at each visit, the participant was given the option of taking the study drug as either a dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation.
Assessments conducted at weeks 2, 8 and 24
Frequency of Cumulative Responses to Administration of Tablet Doses in an Acceptability Assessment
Tidsramme: Assessments conducted at weeks 2, 8 and 24
Acceptability assessments were assessed by Study Staff at study visits and by Participant Caregiver whilst at home. Participants' dose formulations were not restrictive as at each visit, the participant was given the option of taking the study drug as either a dispersible tablet or tablet formulation. At a visit, the participant could have been taking a dispersible tablet and at the next visit the same participant could have been taking a tablet formulation.
Assessments conducted at weeks 2, 8 and 24
Age Effect on Bioavailability DLM
Tidsramme: Approximately Week 2
Plasma concentrations are used to determine age effect on bioavailability. The age covariate describes the fold change in bioavailability for each respective age group of 0-1 year and 1-2 years, with participants aged >2 to <18 years used as the reference group. Study arms were combined for the analysis of age effect.
Approximately Week 2
Age Effect on Fraction Metabolised From Delaminid to DM-6705
Tidsramme: Approximately Week 2
Plasma concentrations are used to determine age effect on bioavailability. The age covariate describes the fold change in bioavailability for each respective age group of 0-1 year and 1-2 years, with participants aged >2 to <18 years used as the reference group. Study arms were combined for the analysis of age effect.
Approximately Week 2
Dose Effect on Bioavailability DLM
Tidsramme: Approximately Week 2
Plasma concentrations are used to determine dose effect on bioavailability. For doses > 50 mg the bioavailability is described by F=(dose/100)-0.66. The participants receiving the dose 100 mg are the reference group and the dose effect of doses 15-20mg, 25mg and 50mg on the bioavailability are compared to the reference group and the fold change is presented. Study arms were combined for the analysis of dose effect.
Approximately Week 2

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbeidspartnere

Otsuka Pharmaceutical Development & Commercialization, Inc.

Etterforskere

  • Studiestol: Ethel Weld, MD, Johns Hopkins University
  • Studiestol: Anthony Garcia-Prats, MD, University of Wisconsin, Madison

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Hjelpsomme linker

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

18. februar 2019

Primær fullføring (Faktiske)

22. april 2025

Studiet fullført (Faktiske)

29. mai 2025

Datoer for studieregistrering

Først innsendt

1. mai 2017

Først innsendt som oppfylte QC-kriteriene

3. mai 2017

Først lagt ut (Faktiske)

4. mai 2017

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

25. juni 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

31. mai 2026

Sist bekreftet

1. mai 2026

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • IMPAACT 2005
  • 20721 (Registeridentifikator: DAIDS-ES Registry Number)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

Individuelle deltakerdata som ligger til grunn resulterer i publisering, etter avidentifikasjon.

IPD-delingstidsramme

Begynner 3 måneder etter publisering og tilgjengelig i hele finansieringsperioden for International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network av NIH.

Tilgangskriterier for IPD-deling

  • Med hvem?

    • Forskere som gir et metodisk forsvarlig forslag til bruk av dataene som er godkjent av IMPAACT Network.

  • For hvilke typer analyser?

    • For å oppnå målene i forslaget godkjent av IMPAACT-nettverket.

  • Ved hvilken mekanisme vil data gjøres tilgjengelig?

    • Forskere kan sende inn en forespørsel om tilgang til data ved å bruke IMPAACT "Data Request"-skjemaet på: https://www.impaactnetwork.org/resources/study-proposals.htm. Forskere av godkjente forslag må signere en IMPAACT-databruksavtale før de mottar dataene.

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL
  • SEVJE

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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Forhold

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