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Avaliando a farmacocinética, a segurança e a tolerabilidade de Delamanid em combinação com regime de base multimedicamentos otimizado (OBR) para tuberculose multirresistente a medicamentos (MDR-TB) em crianças infectadas pelo HIV e não infectadas pelo HIV com MDR-TB

31 de maio de 2026 atualizado por: National Institute of Allergy and Infectious Diseases (NIAID)

Um estudo de fase I/II aberto, de braço único para avaliar a farmacocinética, a segurança e a tolerabilidade de Delamanid em combinação com regime de base multidroga otimizado (OBR) para tuberculose multirresistente (MDR-TB) em infectados pelo HIV e HIV -Crianças não infectadas com MDR-TB

Este estudo avaliará a farmacocinética, a segurança e a tolerabilidade do medicamento anti-tuberculose (TB) delamanid (DLM) em combinação com um regime de base multidrogas otimizado (OBR) para tuberculose multirresistente (MDR-TB) em pacientes infectados pelo HIV e Crianças não infectadas pelo HIV com MDR-TB.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

O objetivo deste estudo é avaliar a farmacocinética, segurança e tolerabilidade do medicamento anti-TB DLM em combinação com OBR para MDR-TB em crianças infectadas pelo HIV e não infectadas pelo HIV com MDR-TB.

Os participantes serão inscritos em uma das quatro faixas etárias: 12 a menos de 18 anos, 6 a menos de 12 anos, 3 a menos de 6 anos ou 0 a menos de 3 anos. Todos os participantes receberão DLM dosado de acordo com sua faixa etária e peso por 24 semanas.

As visitas do estudo ocorrerão na entrada do estudo; Semanas 2 e 4; a cada 4 semanas até a semana 40; e nas semanas 48, 60, 72 e 96. As visitas podem incluir exames físicos; coleta de sangue, urina e escarro; radiografia de tórax; eletrocardiogramas (ECGs); testes auditivos; avaliações de adesão; e questionários de aceitabilidade.

Tipo de estudo

Intervencional

Inscrição (Real)

37

Estágio

  • Fase 2
  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

Não mais velho que 14 anos (Filho)

Aceita Voluntários Saudáveis

Não

Descrição

Critério de inclusão:

  • O pai (ou responsável legal) está disposto e pode fornecer consentimento informado por escrito para a participação da criança no estudo. Além disso, para crianças cujo consentimento é exigido pelas políticas e procedimentos do conselho de revisão institucional/comitê de ética (IRB/CE), a criança está disposta e é capaz de fornecer consentimento por escrito para sua participação no estudo.
  • Idade inferior a 18 anos na inscrição
  • Não infectado pelo HIV ou infectado pelo HIV (consulte o protocolo para obter mais informações sobre este critério)
  • Se infectado pelo HIV: iniciou o regime padrão de terapia antirretroviral (ART) pelo menos duas semanas antes da inscrição (observação: regimes incluindo efavirenz [EFV], nevirapina [NVP], um inibidor de protease potencializado [PI] ou transferência de fita integrase inibidor [INSTI] são permitidos)

  • TB-MDR confirmada ou provável classificada da seguinte forma:

    • TB-MDR confirmada (ou TB monorresistente à rifampicina [RMR-TB], pré-resistente a medicamentos [XDR] ou XDR-TB):

      • TB intratorácica (pulmonar) baseada em radiografia de tórax consistente com TB e/ou qualquer uma das seguintes formas de TB extratorácica:
      • 1) Linfadenite tuberculosa periférica
      • 2) Derrame pleural ou lesões pleurais fibróticas
      • 3) Meningite TB estágio 1
      • 4) TB miliar e abdominal
      • 5) Outras formas não disseminadas de tuberculose (ver também critério de exclusão abaixo)
      • E
      • Confirmação microbiológica de Mycobacterium tuberculosis de qualquer amostra clínica por cultura ou métodos moleculares (incluindo Xpert MTB/RIF)
      • E
      • Resistência a medicamentos demonstrada por métodos genotípicos (moleculares) ou fenotípicos, com qualquer um dos seguintes padrões de resistência:
      • MDR-TB (resistência à rifampicina e à isoniazida)
      • RMR-TB ou onde a resistência adicional à isoniazida (INH) não foi confirmada (isto é, resistência isolada à rifampicina Xpert MTB/RIF)
      • Pré-XDR-TB (MDR-TB mais resistência a uma fluoroquinolona ou a um agente injetável de segunda linha)
      • XDR-TB (MDR-TB mais resistência a uma fluoroquinolona e a um injetável de segunda linha)
      • Nota: RMR-TB, MDR-TB, pré-XDR-TB e XDR-TB são, portanto, referidos coletivamente como "MDR-TB" para fins do protocolo

    • Provável MDR-TB (ou RMR, pré-XDR ou XDR-TB), com inclusão de TB intratorácica e/ou extratorácica conforme listado abaixo:

      • Um diagnóstico presuntivo de TB intratorácica (pulmonar) com base em sintomas ou sinais clínicos bem documentados de TB E radiografia de tórax consistente com TB e/ou qualquer uma das seguintes formas de TB extratorácica:
      • Linfadenite tuberculosa periférica
      • Derrame pleural ou lesões pleurais fibróticas
      • Meningite TB estágio 1
      • TB miliar e abdominal,
      • Outras formas não disseminadas de tuberculose (ver também critério de exclusão abaixo)
      • E
      • Um dos seguintes:
      • Exposição a um caso confirmado de fonte de MDR-TB* (RMR-TB, pré-XDR-TB, XDR-TB)
      • Falha documentada em responder a um regime de primeira linha e onde a adesão foi bem documentada.
      • E
      • A decisão clínica foi tomada para tratar a MDR-TB
      • *Casos fonte confirmados de MDR-TB definidos como casos de TB intratorácica com ou sem TB extratorácica, com confirmação microbiológica de Mycobacterium tuberculosis de qualquer amostra clínica por cultura ou métodos moleculares (incluindo Xpert MTB/RIF) e com resistência a medicamentos demonstrada por métodos genotípicos (moleculares) ou fenotípicos, com qualquer um dos padrões de resistência descritos acima.
  • Nível de albumina superior a 2,8 g/dL nos 30 dias anteriores à inscrição
  • Potássio maior que 3,4 e menor que 5,6 mmol/L; magnésio superior a 0,59 mmol/L dentro de 30 dias antes da inscrição. Observação: os eletrólitos podem ser repostos e uma nova verificação pode ser realizada para atender aos critérios de elegibilidade.
  • Escore Z de IMC maior que -3 para crianças maiores ou iguais a 5 anos de idade; peso para escore Z de comprimento/altura maior que -3 para crianças com menos de 5 anos de idade (usando as últimas pontuações da Organização Mundial da Saúde), na triagem
  • Peso maior ou igual a 3 kg, na triagem
  • Iniciou um regime de tratamento de base otimizado apropriado (OBR) MDR-TB de acordo com a decisão de tratamento de rotina, pelo menos duas semanas, mas não mais de oito semanas antes da inscrição e, na opinião do investigador do centro, está tolerando bem o regime em inscrição. Nota: Um regime de tratamento OBR MDR-TB adequado é definido como incluindo componentes com base nas sensibilidades do isolado infeccioso, se conhecido, e histórico de tratamento anterior, se conhecido. Este regime também deve seguir as diretrizes de tratamento OBR MBR-TB, conforme descrito no protocolo.
  • Se for do sexo masculino e estiver envolvido em atividade sexual que possa levar à gravidez da parceira: Concorda em usar um método contraceptivo de barreira (ou seja, preservativo masculino) durante as primeiras 28 semanas do estudo (ou seja, até quatro semanas após a descontinuação do DLM).
  • Se mulher e com potencial reprodutivo, definido como tendo atingido a menarca e não tendo sido submetido a um procedimento de esterilização documentado (histerectomia, ooforectomia bilateral ou salpingectomia): teste de gravidez negativo na triagem dentro de 14 dias antes da inscrição.
  • Se for do sexo feminino, com potencial reprodutivo (conforme definido no protocolo) e se envolver em atividade sexual que possa levar à gravidez: concorda em evitar a gravidez e usar uma das seguintes formas de controle de natalidade enquanto estiver recebendo DLM e por um mês após interromper o DLM : preservativos, diafragma ou capuz cervical, dispositivo intra-uterino (DIU), contracepção hormonal. O método selecionado deve ser iniciado antes da inscrição.

Critério de exclusão:

  • Alergia conhecida a quaisquer nitroimidazóis ou derivados de nitroimidazóis
  • Uso ativo de medicamentos proibidos listados no protocolo, até 3 dias após a inscrição

  • O participante tem um histórico de qualquer um dos seguintes, conforme determinado pelo investigador do centro ou pessoa designada com base no relatório materno e nos registros médicos disponíveis:

    • Uma arritmia cardíaca significativa que requer medicação ou um histórico de doença cardíaca (insuficiência cardíaca, doença arterial coronariana) que aumenta o risco de Torsade de Pointes
    • Doença gastrointestinal (GI), metabólica, neuropsiquiátrica, renal ou endócrina significativa na triagem que, na opinião do investigador, impediria a participação segura no estudo e/ou avaliação dos desfechos primários
    • DLM anterior ou exposição a pretomanida
    • Nota: Os participantes podem ter recebido até 14 + 3 dias (ou seja, até 17 dias) de DLM antes da inscrição
  • Eletrocardiograma (ECG) anormal (incluindo QTcF [valor médio do intervalo QT, corrigido usando correção de Fredericia, no ECG realizado em triplicata] maior ou igual a 450 ms, bloqueio atrioventricular ou QRS prolongado maior ou igual a 120 ms) na triagem
  • Pontuação de Karnofsky inferior a 30% para participantes com idade igual ou superior a 16 anos ou pontuação de jogo de Lansky inferior a 30% para participantes com idade inferior a 16 anos, na triagem
  • Ingestão de álcool que, na opinião do investigador do estudo, poderia potencialmente interferir na participação no estudo e/ou apresentar questões de segurança com o uso de DLM
  • Lactantes com planos de amamentar, na matrícula
  • Meningite tuberculosa (TBM) Estágio 2 ou 3, ou TB osteoarticular na triagem
  • Co-inscrito em qualquer outro estudo envolvendo regimes farmacológicos, na triagem
  • Se exposto ao HIV e com menos de 2 anos de idade: Amamentação no momento da inscrição

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Não randomizado
  • Modelo Intervencional: Atribuição de grupo único
  • Mascaramento: Nenhum (rótulo aberto)

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 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.
Medicamento: 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)

Outros nomes:
  • DLM
Medicamento: 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.
Experimental: 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.
Medicamento: 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)

Outros nomes:
  • DLM
Medicamento: 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.
Experimental: 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.
Medicamento: 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)

Outros nomes:
  • DLM
Medicamento: 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.
Experimental: 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.
Medicamento: 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)

Outros nomes:
  • DLM
Medicamento: 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.

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Percentage of Participants With Adverse Events of ≥ Grade 3 Severity
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Percentage of Participants With Adverse Events ≥ Grade 3 Severity
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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.
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

National Institute of Allergy and Infectious Diseases (NIAID)

Colaboradores

Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigadores

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

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Links úteis

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo (Real)

18 de fevereiro de 2019

Conclusão Primária (Real)

22 de abril de 2025

Conclusão do estudo (Real)

29 de maio de 2025

Datas de inscrição no estudo

Enviado pela primeira vez

1 de maio de 2017

Enviado pela primeira vez que atendeu aos critérios de CQ

3 de maio de 2017

Primeira postagem (Real)

4 de maio de 2017

Atualizações de registro de estudo

Última Atualização Postada (Real)

25 de junho de 2026

Última atualização enviada que atendeu aos critérios de controle de qualidade

31 de maio de 2026

Última verificação

1 de maio de 2026

Mais Informações

Termos relacionados a este estudo

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • IMPAACT 2005
  • 20721 (Identificador de registro: DAIDS-ES Registry Number)

Plano para dados de participantes individuais (IPD)

Planeja compartilhar dados de participantes individuais (IPD)?

SIM

Descrição do plano IPD

Dados individuais dos participantes que fundamentam os resultados na publicação, após a desidentificação.

Prazo de Compartilhamento de IPD

A partir de 3 meses após a publicação e disponível durante todo o período de financiamento da Rede Internacional de Ensaios Clínicos em AIDS Materno-Pediátrica em Adolescentes (IMPAACT) do NIH.

Critérios de acesso de compartilhamento IPD

  • Com quem?

    • Pesquisadores que apresentem uma proposta metodologicamente sólida de uso dos dados que seja aprovada pela Rede IMPAACT.

  • Para quais tipos de análises?

    • Atingir os objetivos da proposta aprovada pela Rede IMPAACT.

  • Por qual mecanismo os dados serão disponibilizados?

    • Os pesquisadores podem enviar uma solicitação de acesso aos dados usando o formulário IMPAACT "Solicitação de Dados" em: https://www.impaactnetwork.org/resources/study-proposals.htm. Os pesquisadores das propostas aprovadas precisarão assinar um Acordo de Uso de Dados do IMPAACT antes de receber os dados.

Tipo de informação de suporte de compartilhamento de IPD

  • PROTOCOLO DE ESTUDO
  • SEIVA

Informações sobre medicamentos e dispositivos, documentos de estudo

Estuda um medicamento regulamentado pela FDA dos EUA

Sim

Estuda um produto de dispositivo regulamentado pela FDA dos EUA

Não

produto fabricado e exportado dos EUA

Não

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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