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Utvärdering av farmakokinetiken, säkerheten och tolerabiliteten för delamanid i kombination med optimerad multiläkemedelsbakgrundsregimen (OBR) för multiresistent tuberkulos (MDR-TB) hos HIV-infekterade och HIV-oinfekterade barn med MDR-TB

31 maj 2026 uppdaterad av: National Institute of Allergy and Infectious Diseases (NIAID)

En öppen fas I/II studie med enarmstyp för att utvärdera farmakokinetiken, säkerheten och tolerabiliteten för Delamanid i kombination med optimerad multiläkemedelsbakgrundsregimen (OBR) för multiresistent tuberkulos (MDR-TB) hos HIV-infekterade och HIV -Oinfekterade barn med MDR-TB

Denna studie kommer att utvärdera farmakokinetiken, säkerheten och tolerabiliteten av läkemedlet mot tuberkulos (TB) delamanid (DLM) i kombination med en optimerad multiläkemedelsbakgrundsregim (OBR) för multiresistent tuberkulos (MDR-TB) hos HIV-infekterade och HIV-oinfekterade barn med MDR-TB.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

Syftet med denna studie är att utvärdera farmakokinetiken, säkerheten och tolerabiliteten av anti-TB-läkemedlet DLM i kombination med OBR för MDR-TB hos HIV-infekterade och HIV-oinfekterade barn med MDR-TB.

Deltagare kommer att skrivas in i en av fyra ålderskohorter: 12 till mindre än 18 år, 6 till mindre än 12 år, 3 till mindre än 6 år eller 0 till mindre än 3 år. Alla deltagare kommer att få DLM doserat efter deras åldersgrupp och vikt i 24 veckor.

Studiebesök kommer att ske vid studiestart; Vecka 2 och 4; var 4:e vecka till och med vecka 40; och veckorna 48, 60, 72 och 96. Besök kan innefatta fysiska undersökningar; blod-, urin- och sputumuppsamling; bröströntgen; elektrokardiogram (EKG); hörseltest; efterlevnadsbedömningar; och acceptans frågeformulär.

Studietyp

Interventionell

Inskrivning (Faktisk)

37

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • 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)

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

Inte äldre än 14 år (Barn)

Tar emot friska volontärer

Nej

Beskrivning

Inklusionskriterier:

  • Förälder (eller vårdnadshavare) är villig och kan ge skriftligt informerat samtycke för barns deltagande i studien. Dessutom, för barn vars samtycke krävs enligt riktlinjer och procedurer för institutionell granskningsnämnd/etikkommitté (IRB/EC), är barnet villig och kan ge skriftligt medgivande för sitt deltagande i studien.
  • Ålder mindre än 18 år vid inskrivningen
  • HIV-oinfekterad eller HIV-infekterad (se protokollet för mer information om detta kriterium)
  • Om HIV-infekterad: Inledde standardbehandlingen antiretroviral terapi (ART) minst två veckor före inskrivningen (notera: kurer inklusive efavirenz [EFV], nevirapin [NVP], en boostad proteashämmare [PI] eller integrassträngöverföring hämmare [INSTI] är tillåtna)

  • Bekräftad eller trolig MDR-TB klassificerad enligt följande:

    • Bekräftad MDR-TB (eller rifampicin monoresistent TB [RMR-TB], pre-extensivt läkemedelsresistent [XDR] eller XDR-TB):

      • Intra-thorax (pulmonell) TB baserad på lungröntgen som överensstämmer med TB och/eller någon av följande former av extrathorax TB:
      • 1) Perifer TB-lymfadenit
      • 2) Pleurautgjutning eller fibrotiska pleuralasioner
      • 3) Steg 1 TB meningit
      • 4) Miliär och buken TB
      • 5) Andra icke-spridda former av TB-sjukdom (se även uteslutningskriterium nedan)
      • OCH
      • Mikrobiologisk bekräftelse av Mycobacterium tuberculosis från alla kliniska prover genom antingen odling eller molekylära metoder (inklusive Xpert MTB/RIF)
      • OCH
      • Läkemedelsresistens påvisad genom genotypiska (molekylära) eller fenotypiska metoder, med något av följande resistensmönster:
      • MDR-TB (resistens mot både rifampicin och isoniazid)
      • RMR-TB eller där ytterligare isoniazidresistens (INH) inte har bekräftats (d.v.s. isolerad Xpert MTB/RIF rifampicinresistens)
      • Pre-XDR-TB (MDR-TB plus resistens mot antingen en fluorokinolon eller ett andra linjens injicerbart medel)
      • XDR-TB (MDR-TB plus resistens mot både en fluorokinolon och en andra linjens injicerbar)
      • Obs: RMR-TB, MDR-TB, pre-XDR-TB och XDR-TB kallas därför gemensamt för "MDR-TB" för protokollets syften

    • Trolig MDR-TB (eller RMR, pre-XDR eller XDR-TB), med inkluderande av intrathorakal och/eller extrathorax TB enligt nedan:

      • En presumtiv diagnos av intratorakal (pulmonell) tuberkulos baserad på väldokumenterade kliniska symtom eller tecken på tuberkulos OCH röntgen av bröstkorgen som överensstämmer med tuberkulos och/eller någon av följande former av extratorakal tuberkulos:
      • Perifer TB lymfadenit
      • Pleurautgjutning eller fibrotiska pleuralasioner
      • Steg 1 TB meningit
      • Miliär och buken TB,
      • Andra icke-spridda former av TB-sjukdom (se även uteslutningskriterium nedan)
      • OCH
      • En av följande:
      • Exponering för ett bekräftat MDR-TB-källfall* (RMR-TB, pre-XDR-TB, XDR-TB)
      • Dokumenterad underlåtenhet att svara på en förstahandsbehandling, och där följsamheten var väl dokumenterad.
      • OCH
      • Det kliniska beslutet har tagits att behandla för MDR-TB
      • * Bekräftade fall av MDR-TB-källa definierat som ett fall med intratorakal tuberkulos med eller utan extratorakal tuberkulos, med mikrobiologisk bekräftelse av Mycobacterium tuberculosis från vilket kliniskt prov som helst med antingen odling eller molekylära metoder (inklusive Xpert MTB/RIF), och med läkemedelsresistens påvisad genom genotypiska (molekylära) eller fenotypiska metoder, med något av resistensmönstren som beskrivits ovan.
  • Albuminnivå högre än 2,8 g/dL inom 30 dagar före registrering
  • Kalium större än 3,4 och mindre än 5,6 mmol/L; magnesium större än 0,59 mmol/L inom 30 dagar före inskrivningen. Obs: Elektrolyter kan fyllas på och en ny kontroll kan utföras för att uppfylla behörighetskriterierna.
  • BMI Z-poäng större än -3 för barn äldre än eller lika med 5 år; vikt för längd/höjd Z-poäng större än -3 för barn under 5 år (med senaste Världshälsoorganisationens poäng), vid screening
  • Vikt större än eller lika med 3 kg, vid screening
  • Har påbörjat en lämplig optimerad bakgrundsregim (OBR) MDR-TB-behandlingsregim enligt rutinbehandlingsbeslut, minst två veckor men inte mer än åtta veckor före inskrivningen, och enligt platsutredarens uppfattning tolererar regimen väl vid inskrivning. Obs: En lämplig OBR MDR-TB-behandlingsregim definieras som att inkludera komponenter baserade på känsligheten hos det infekterande isolatet, om känt, och tidigare behandlingshistorik, om känd. Denna regim bör också följa OBR MBR-TB-behandlingsriktlinjerna som beskrivs i protokollet.
  • Om man är man och ägnar sig åt sexuell aktivitet som kan leda till att den kvinnliga partnern blir gravid: Går med på att använda en barriärmetod för preventivmedel (dvs. manlig kondom) under de första 28 veckorna av studien (dvs fram till fyra veckor efter avslutad DLM).
  • Om kvinna och reproduktionspotential, definierad som att ha nått menarken och inte genomgått ett dokumenterat steriliseringsförfarande (hysterektomi, bilateral ooforektomi eller salpingektomi): Negativt graviditetstest vid screening inom 14 dagar före inskrivning.
  • Om kvinna, med reproduktionspotential (enligt definitionen i protokollet) och ägnar sig åt sexuell aktivitet som kan leda till graviditet: Går med på att undvika graviditet och att använda en av följande former av preventivmedel under behandling med DLM och i en månad efter att ha avslutat DLM : kondomer, diafragma eller livmoderhalsmössa, intrauterin enhet (IUD), hormonellt baserad preventivmedel. Den valda metoden måste initieras innan registrering.

Exklusions kriterier:

  • Känd allergi mot nitroimidazoler eller nitroimidazolderivat
  • Aktiv användning av förbjudna läkemedel som anges i protokollet, inom 3 dagar efter registreringen

  • Deltagaren har en historia av något av följande, som fastställts av platsutredaren eller utses baserat på moderns rapport och tillgängliga medicinska journaler:

    • En betydande hjärtarytmi som kräver medicinering eller en historia av hjärtsjukdom (hjärtsvikt, kranskärlssjukdom) som ökar risken för Torsade de Pointes
    • Betydande gastrointestinal (GI), metabolisk, neuropsykiatrisk, njur- eller endokrin sjukdom vid screening som enligt utredarens åsikt skulle utesluta säkert deltagande i prövningen och/eller bedömningen av primära effektmått
    • Tidigare exponering för DLM eller pretomanid
    • Obs: Deltagare kan ha fått upp till 14 + 3 dagar (dvs. upp till 17 dagar) av DLM före registreringen
  • Onormalt elektrokardiogram (EKG) (inklusive QTcF [medelvärde för QT-intervall, korrigerat med Fredericia-korrigering, på EKG utfört i tre exemplar] större än eller lika med 450 ms, atrioventrikulär blockering eller förlängd QRS större än eller lika med 120 ms) vid screening
  • Karnofsky poäng mindre än 30 % för deltagare äldre än eller lika med 16 år eller Lansky play poäng mindre än 30 % för deltagare under 16 år, vid screening
  • Alkoholintag som enligt studieutredaren potentiellt skulle kunna störa studiedeltagandet och/eller införa säkerhetsproblem vid användning av DLM
  • Ammande med planer på att amma, vid inskrivning
  • Tuberkulös meningit (TBM) Steg 2 eller 3, eller osteoartikulär TB vid screening
  • Samtidigt inskriven i någon annan prövning som involverar farmakologiska regimer, vid screening
  • Om HIV-exponerad och yngre än 2 år: Amning vid inskrivning

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: Icke-randomiserad
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Läkemedel: 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)

Andra namn:
  • DLM
Läkemedel: 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.
Experimentell: 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.
Läkemedel: 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)

Andra namn:
  • DLM
Läkemedel: 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.
Experimentell: 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.
Läkemedel: 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)

Andra namn:
  • DLM
Läkemedel: 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.
Experimentell: 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.
Läkemedel: 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)

Andra namn:
  • DLM
Läkemedel: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Percentage of Participants With Adverse Events of ≥ Grade 3 Severity
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Percentage of Participants With Adverse Events ≥ Grade 3 Severity
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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.
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: 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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Samarbetspartners

Otsuka Pharmaceutical Development & Commercialization, Inc.

Utredare

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

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Användbara länkar

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)

18 februari 2019

Primärt slutförande (Faktisk)

22 april 2025

Avslutad studie (Faktisk)

29 maj 2025

Studieregistreringsdatum

Först inskickad

1 maj 2017

Först inskickad som uppfyllde QC-kriterierna

3 maj 2017

Första postat (Faktisk)

4 maj 2017

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

25 juni 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

31 maj 2026

Senast verifierad

1 maj 2026

Mer information

Termer relaterade till denna studie

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

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

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

JA

IPD-planbeskrivning

Enskilda deltagardata som ligger till grund resulterar i publiceringen, efter avidentifiering.

Tidsram för IPD-delning

Börjar 3 månader efter publicering och tillgänglig under hela finansieringsperioden för International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) Network av NIH.

Kriterier för IPD Sharing Access

  • Med vem?

    • Forskare som ger ett metodologiskt välgrundat förslag för användning av data som är godkänt av IMPAACT Network.

  • För vilka typer av analyser?

    • Att uppnå målen i förslaget som godkänts av IMPAACT-nätverket.

  • Genom vilken mekanism kommer data att göras tillgängliga?

    • Forskare kan lämna in en begäran om tillgång till data med hjälp av IMPAACT "Data Request"-formuläret på: https://www.impaactnetwork.org/resources/study-proposals.htm. Forskare av godkända förslag måste underteckna ett IMPAACT-dataanvändningsavtal innan de får uppgifterna.

IPD-delning som stöder informationstyp

  • STUDY_PROTOCOL
  • SAV

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

produkt tillverkad i och exporterad från U.S.A.

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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