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Evaluering af farmakokinetikken, sikkerheden og tolerabiliteten af ​​delamanid i kombination med optimeret multilægemiddel-baggrundsregime (OBR) for multiresistent tuberkulose (MDR-TB) hos HIV-inficerede og HIV-ikke-inficerede børn med MDR-TB

31. maj 2026 opdateret af: National Institute of Allergy and Infectious Diseases (NIAID)

Et fase I/II åbent enkeltarmsstudie til evaluering af farmakokinetikken, sikkerheden og tolerabiliteten af ​​delamanid i kombination med optimeret multilægemiddelbaggrundsregime (OBR) for multiresistent tuberkulose (MDR-TB) hos HIV-inficerede og HIV -Uinficerede børn med MDR-TB

Denne undersøgelse vil evaluere farmakokinetikken, sikkerheden og tolerabiliteten af ​​anti-tuberkulose (TB) lægemidlet delamanid (DLM) i kombination med et optimeret multilægemiddel baggrundsregime (OBR) for multilægemiddelresistent tuberkulose (MDR-TB) hos HIV-inficerede og HIV-uinficerede børn med MDR-TB.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Formålet med denne undersøgelse er at evaluere farmakokinetikken, sikkerheden og tolerabiliteten af ​​anti-TB-lægemidlet DLM i kombination med OBR for MDR-TB hos HIV-inficerede og HIV-uinficerede børn med MDR-TB.

Deltagerne vil blive tilmeldt en af ​​fire alderskohorter: 12 til under 18 år, 6 til under 12 år, 3 til mindre end 6 år eller 0 til under 3 år. Alle deltagere vil modtage DLM doseret efter deres aldersgruppe og vægt i 24 uger.

Studiebesøg vil finde sted ved studiestart; Uge 2 og 4; hver 4. uge til og med uge 40; og i uge 48, 60, 72 og 96. Besøg kan omfatte fysiske undersøgelser; blod-, urin- og sputumopsamling; røntgenbilleder af brystet; elektrokardiogrammer (EKG'er); høreprøver; vurderinger af overholdelse; og acceptabel spørgeskemaer.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

37

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

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

Studiesteder

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

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

Ikke ældre end 14 år (Barn)

Tager imod sunde frivillige

Ingen

Beskrivelse

Inklusionskriterier:

  • Forælder (eller værge) er villig og i stand til at give skriftligt informeret samtykke til børns deltagelse i undersøgelsen. For børn, hvis samtykke er påkrævet i henhold til politikker og procedurer for institutionelle revisionsnævn/etiske udvalg (IRB/EC), er barnet villig og i stand til at give skriftligt samtykke til sin deltagelse i undersøgelsen.
  • Alder under 18 år ved indskrivning
  • HIV-uinficeret eller HIV-inficeret (se protokollen for mere information om dette kriterium)
  • Hvis HIV-inficeret: Påbegyndte standardbehandlingen antiretroviral terapi (ART) mindst to uger før tilmelding (bemærk: regimer inklusive efavirenz [EFV], nevirapin [NVP], en boostet proteasehæmmer [PI] eller integrasestreng transfer inhibitor [INSTI] er tilladt)

  • Bekræftet eller sandsynlig MDR-TB klassificeret som følger:

    • Bekræftet MDR-TB (eller rifampicin mono-resistent TB [RMR-TB], præ-ekstensivt lægemiddelresistent [XDR] eller XDR-TB):

      • Intra-thorax (pulmonal) TB baseret på røntgenbillede af thorax i overensstemmelse med TB og/eller en af ​​følgende former for ekstrathorakal TB:
      • 1) Perifer TB lymfadenitis
      • 2) Pleural effusion eller fibrotiske pleuralæsioner
      • 3) Stadie 1 TB meningitis
      • 4) Miliær og abdominal TB
      • 5) Andre ikke-udbredte former for TB-sygdom (se også udelukkelseskriteriet nedenfor)
      • OG
      • Mikrobiologisk bekræftelse af Mycobacterium tuberculosis fra enhver klinisk prøve ved enten kultur eller molekylære metoder (inklusive Xpert MTB/RIF)
      • OG
      • Lægemiddelresistens påvist ved genotypiske (molekylære) eller fænotypiske metoder med et af følgende resistensmønstre:
      • MDR-TB (resistens over for både rifampicin og isoniazid)
      • RMR-TB eller hvor yderligere isoniazid (INH) resistens ikke er blevet bekræftet (dvs. isoleret Xpert MTB/RIF rifampicinresistens)
      • Pre-XDR-TB (MDR-TB plus resistens over for enten en fluoroquinolon eller en anden linje injicerbart middel)
      • XDR-TB (MDR-TB plus resistens over for både en fluoroquinolon og en anden linje injicerbar)
      • Bemærk: RMR-TB, MDR-TB, pre-XDR-TB og XDR-TB omtales derfor samlet som "MDR-TB" i forbindelse med protokollen

    • Sandsynlig MDR-TB (eller RMR, præ-XDR eller XDR-TB), med inklusion af intrathorax og/eller ekstrathorakal TB som anført nedenfor:

      • En formodet diagnose af intrathorax (pulmonal) TB baseret på veldokumenterede kliniske symptomer eller tegn på TB OG røntgenbillede af thorax i overensstemmelse med TB og/eller en af ​​følgende former for ekstrathorakal TB:
      • Perifer TB lymfadenitis
      • Pleural effusion eller fibrotiske pleurale læsioner
      • Fase 1 TB meningitis
      • Miliær og abdominal TB,
      • Andre ikke-udbredte former for TB-sygdom (se også eksklusionskriteriet nedenfor)
      • OG
      • En af følgende:
      • Eksponering for et bekræftet MDR-TB-kildetilfælde* (RMR-TB, pre-XDR-TB, XDR-TB)
      • Dokumenteret manglende respons på en førstelinjebehandling, og hvor overholdelse var veldokumenteret.
      • OG
      • Den kliniske beslutning er truffet for at behandle for MDR-TB
      • * Bekræftede MDR-TB-kildetilfælde defineret som et tilfælde med intrathorakal TB med eller uden ekstrathorakal TB, med mikrobiologisk bekræftelse af Mycobacterium tuberculosis fra enhver klinisk prøve ved enten kultur eller molekylære metoder (herunder Xpert MTB/RIF) og med lægemiddelresistens påvist ved genotypiske (molekylære) eller fænotypiske metoder med et hvilket som helst af de ovenfor beskrevne resistensmønstre.
  • Albuminniveau større end 2,8 g/dL inden for 30 dage før tilmelding
  • Kalium større end 3,4 og mindre end 5,6 mmol/L; magnesium større end 0,59 mmol/L inden for 30 dage før tilmelding. Bemærk: Elektrolytter kan udfyldes, og der kan udføres en genkontrol for at opfylde berettigelseskriterierne.
  • BMI Z-score større end -3 for børn større end eller lig med 5 år; vægt for længde/højde Z-score større end -3 for børn under 5 år (ved hjælp af seneste World Health Organization-resultater), ved screening
  • Vægt større end eller lig med 3 kg ved screening
  • Har påbegyndt et passende optimeret baggrundsregime (OBR) MDR-TB-behandlingsregime i henhold til rutinemæssig behandlingsbeslutning, mindst to uger, men ikke mere end otte uger før tilmelding, og tolererer efter undersøgelsesstedets vurdering regimet godt kl. indskrivning. Bemærk: Et passende OBR MDR-TB-behandlingsregime er defineret som at inkludere komponenter baseret på følsomheden af ​​det inficerende isolat, hvis kendt, og tidligere behandlingshistorie, hvis kendt. Dette regime bør også følge retningslinjerne for OBR MBR-TB-behandling som beskrevet i protokollen.
  • Hvis en mand og deltager i seksuel aktivitet, der kan føre til graviditet af den kvindelige partner: Indvilliger i at bruge en barrieremetode til prævention (dvs. mandligt kondom) gennem de første 28 uger på undersøgelsen (dvs. indtil fire uger efter seponering af DLM).
  • Hvis kvinde og af reproduktionspotentiale, defineret som at have nået menarche og ikke have gennemgået en dokumenteret steriliseringsprocedure (hysterektomi, bilateral oophorektomi eller salpingektomi): Negativ graviditetstest ved screening inden for 14 dage før indskrivning.
  • Hvis kvinde, af reproduktionspotentiale (som defineret i protokollen), og involverer sig i seksuel aktivitet, der kan føre til graviditet: Indvilliger i at undgå graviditet og at bruge en af ​​følgende former for prævention, mens du modtager DLM og i en måned efter ophør med DLM : kondomer, mellemgulv eller cervikal hætte, intrauterin enhed (IUD), hormonbaseret prævention. Den valgte metode skal påbegyndes inden tilmelding.

Ekskluderingskriterier:

  • Kendt allergi over for alle nitroimidazoler eller nitroimidazolderivater
  • Aktiv brug af forbudte medicin anført i protokollen inden for 3 dage efter tilmelding

  • Deltageren har en historie med et eller flere af følgende, som bestemt af stedets efterforsker eller udpeget baseret på moderens rapport og tilgængelige lægejournaler:

    • En betydelig hjertearytmi, der kræver medicin eller en historie med hjertesygdom (hjertesvigt, koronararteriesygdom), der øger risikoen for Torsade de Pointes
    • Betydelig gastrointestinal (GI), metabolisk, neuropsykiatrisk, nyre- eller endokrin sygdom ved screening, der efter investigatorens mening ville udelukke sikker deltagelse i forsøget og/eller vurderingen af ​​primære endepunkter
    • Tidligere DLM eller pretomanid eksponering
    • Bemærk: Deltagere kan have modtaget op til 14 + 3 dage (dvs. op til 17 dage) af DLM før tilmelding
  • Unormalt elektrokardiogram (EKG) (inklusive QTcF [middelværdi af QT-interval, korrigeret ved hjælp af Fredericia-korrektion, på EKG udført i tre eksemplarer] større end eller lig med 450 ms, atrioventrikulær blokering eller forlænget QRS større end eller lig med 120 ms) ved screening
  • Karnofsky scorer mindre end 30 % for deltagere over eller lig med 16 år eller Lansky play score mindre end 30 % for deltagere under 16 år ved screening
  • Alkoholindtag, som efter undersøgelsesforskerens mening potentielt kunne forstyrre undersøgelsesdeltagelsen og/eller indføre sikkerhedsproblemer ved brug af DLM
  • Ammende med planer om at amme, ved tilmelding
  • Tuberkuløs meningitis (TBM) trin 2 eller 3, eller osteoartikulær TB ved screening
  • Samregistreret i ethvert andet forsøg, der involverer farmakologiske regimer, ved screening
  • Ved hiv-eksponeret og under 2 år: Amning ved tilmelding

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: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: 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 navne:
  • DLM
Medicin: 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.
Eksperimentel: 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.
Medicin: 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 navne:
  • DLM
Medicin: 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.
Eksperimentel: 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.
Medicin: 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 navne:
  • DLM
Medicin: 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.
Eksperimentel: 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.
Medicin: 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 navne:
  • DLM
Medicin: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
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

Samarbejdspartnere og efterforskere

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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbejdspartnere

Otsuka Pharmaceutical Development & Commercialization, Inc.

Efterforskere

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

Publikationer og nyttige links

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

Hjælpsomme links

Datoer for undersøgelser

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

Studer store datoer

Studiestart (Faktiske)

18. februar 2019

Primær færdiggørelse (Faktiske)

22. april 2025

Studieafslutning (Faktiske)

29. maj 2025

Datoer for studieregistrering

Først indsendt

1. maj 2017

Først indsendt, der opfyldte QC-kriterier

3. maj 2017

Først opslået (Faktiske)

4. maj 2017

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

25. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

31. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

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

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Individuelle deltagerdata, der ligger til grund, resulterer i offentliggørelsen efter afidentifikation.

IPD-delingstidsramme

Begyndende 3 måneder efter offentliggørelsen og tilgængelig i hele finansieringsperioden for International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network af NIH.

IPD-delingsadgangskriterier

  • Med hvem?

    • Forskere, der giver et metodisk forsvarligt forslag til brug af data, som er godkendt af IMPAACT Network.

  • Til hvilke typer analyser?

    • At nå målene i forslaget godkendt af IMPAACT-netværket.

  • Ved hvilken mekanisme vil data blive gjort tilgængelige?

    • Forskere kan indsende en anmodning om adgang til data ved hjælp af IMPAACT "Data Request"-formularen på: https://www.impaactnetwork.org/resources/study-proposals.htm. Forskere af godkendte forslag skal underskrive en IMPAACT-databrugsaftale, før de modtager dataene.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

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

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