Study to Investigate the Pharmacokinetics and Safety of Cadazolid in Patients With Clostridium Difficile Infection
31 de janeiro de 2014 atualizado por: Actelion
A Phase 1, Open-label, Single Oral Dose Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Cadazolid in Patients With Severe Clostridium Difficile Infection (CDI)
The study investigated the pharmacokinetics, safety, and tolerability of cadazolid in subjects with severe Clostridium difficile diarrhea (CDAD) and whether this influenced the quantity of cadazolid absorbed into the systemic circulation.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
6
Estágio
- 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
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Zagreb, Croácia, 1000
- Clinical Hospital for Infective Disease
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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
18 anos a 80 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Signed informed consent prior to any study-mandated procedure.
- Non-pregnant females were to remain non-pregnant for 1 month after the end of the study. Female subjects of child-bearing potential must have had a negative serum pregnancy test at screening and must have used a reliable method of contraception
- Subjects with severe CDAD; Clostridium difficile infection (CDI) must have been microbiologically proven, using a validated enzyme-linked immunosorbent assay (ELISA) for the detection of C. difficile toxin A (TcdA) and/or C. difficile toxin B (TcdB). The severity of CDAD was assessed according to the current European Union guidelines - European Society of Clinical Microbiology and Infectious Diseases (ESCMID).
- Received oral vancomycin or oral/intravenous (i.v.) metronidazole therapy for the treatment of CDAD.
- Ability to communicate well with the investigator in the local language, and to understand and comply with the requirements of the study.
Exclusion Criteria:
- Known hypersensitivity to any excipients of the drug formulation.
- Clinical evidence of any relevant disease other than CDAD and/or existence of any surgical or medical condition that might interfere with the absorption, distribution, metabolism or excretion of the study drug.
- Veins unsuitable for i.v. puncture on either arm (e.g., veins that are difficult to locate, access, or puncture; veins with a tendency to rupture during or after puncture).
- Subjects with rare hereditary fructose intolerance, glucose-galactose malabsorption, saccharase-isomaltase deficiency or previously undiagnosed diabetes mellitus.
- Subjects who have a life-threatening condition, which may be related to CDAD or other underlying illness.
- Any clinically relevant electrocardiogram (ECG) abnormality at screening.
- Subjects who were unable to swallow or have difficulty swallowing.
- Subjects with vomiting, ileus or not passing stool.
- Likelihood of death within 72 hours from any cause.
- Life-threatening or fulminant CDAD (White blood cell count > 30 × 10^9/L; temperature > 40 °C; or septic shock, peritoneal signs or significant dehydration).
- History of ulcerative colitis or Crohn's disease.
- Loss of 250 mL or more of blood within 3 months prior to screening.
- Positive results from the hepatitis serology, except for vaccinated subjects, at screening.
- Positive results from the human immunodeficiency virus (HIV) serology at screening.
- Legal incapacity or limited legal capacity at screening.
- Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
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
- Alocação: N / D
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: Cadazolid
Single oral dose of 3000 mg.
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Cadazolid was provided as dry powder for oral suspension (Amber glass bottles of 60 mL).
The powder was reconstituted with tap water by a pharmacist immediately prior to dispensing to subjects.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Maximum plasma concentration (Cmax) of cadazolid
Prazo: 144 hours
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Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing.
Cmax was calculated on the basis of the blood sampling time points.
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144 hours
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Time to reach maximum plasma concentration (tmax) of cadazolid
Prazo: 144 hours
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Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing.
tmax was calculated on the basis of the blood sampling time points.
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144 hours
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Area under the plasma concentration-time curve (AUC(0-144h)) of cadazolid
Prazo: 144 hours
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Blood samples for pharmacokinetic analysis taken immediately prior to dosing with cadazolid, and at 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, and 144 hours after dosing.
AUC(0-144) was calculated according to the linear trapezoidal rule using the measured concentration-time values above the limit of quantification.
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144 hours
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Unchanged cadazolid in urine up to Day 7
Prazo: 144 hours
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Urine was collected into standard-weight polyethylene containers over the following time intervals: 0-12 h, 12-24 h, 24-36 h, 36-48 h, 48-72 h, 72-96 h, 96-120 h, and 120-144 h.
The concentration of cadazolid was determined using validated liquid chromatography-tandem mass spectrometry assays.
The amount of drug excreted in the urine was obtained by multiplying the concentration of drug by the volume of matrix collected.
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144 hours
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Unchanged cadazolid in faeces up to Day 7
Prazo: 144 hours
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Faeces were collected in pre-weighed polypropylene boxes.
The concentration of cadazolid was determined using validated liquid chromatography-tandem mass spectrometry assays.
The amount of drug excreted in the faeces was obtained by multiplying the concentration of drug by the volume of matrix collected.
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144 hours
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change from baseline up to Day 7 in systolic blood pressure (SBP)
Prazo: 144 hours
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Blood pressure (systolic and diastolic) and pulse rate were measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm = writing arm).
Measurements were recorded in the supine position after the subject had rested for a 5-minute period.
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144 hours
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Change from baseline up to Day 7 in diastolic blood pressure (DBP)
Prazo: 144 hours
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Blood pressure (systolic and diastolic) and pulse rate were measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm = writing arm).
Measurements were recorded in the supine position after the subject had rested for a 5-minute period.
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144 hours
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Change from baseline up to Day 7 in pulse rate
Prazo: 144 hours
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Blood pressure (systolic and diastolic) and pulse rate were measured using an automatic oscillometric device, always on the leading arm (i.e., leading arm = writing arm).
Measurements were recorded in the supine position after the subject had rested for a 5-minute period.
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144 hours
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Change from baseline to Day 7 in body weight
Prazo: 144 hours
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Body weight was measured using the same weighing scales.
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144 hours
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Change from baseline up to Day 7 in heart rate
Prazo: 144 hours
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Heart rate was determined from standard 12-lead electrocardiographs (ECGs) recorded in the supine position, after a 5-minute period of resting.
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144 hours
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Change from baseline up to Day 7 in PQ interval (time interval from the beginning of the P wave to the beginning of the QRS complex)
Prazo: 144 hours
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PQ interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
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144 hours
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Change from baseline up to Day 7 in QRS duration (time interval from the beginning of the Q wave to the end of the S wave)
Prazo: 144 hours
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QRS duration was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
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144 hours
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Change from baseline up to Day 7 in QT (time interval from beginning of the Q wave until end of the T wave)
Prazo: 144 hours
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QT interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
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144 hours
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Change from baseline up to Day 7 in QT interval according to Bazett's correction (QTcB)
Prazo: 144 hours
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QTcB interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
The QTcB interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Bazett's formula (QTcB = QT/RR^0.5
where RR is 60/heart rate)
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144 hours
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Change from baseline up to Day 7 in QT interval according to Fridericia's correction (QTcF)
Prazo: 144 hours
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QTcF interval was determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
The QTcF interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Fridericia's formula (QTcB = QT/RR^0.33
where RR is 60/heart rate)
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144 hours
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Frequency of treatment-emergent ECG abnormalities from up to Day 7
Prazo: 144 hours
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Treatment-emergent abnormalities were determined from standard 12-lead ECGs recorded in the supine position, after a 5-minute period of resting.
An ECG abnormality was considered treatment-emergent if it was not present during the screening period and/or at time of pre-dose assessment.
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144 hours
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Diretor de estudo: Alison Mackie, MSc, Actelion
Publicações e links úteis
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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
1 de agosto de 2012
Conclusão Primária (Real)
1 de setembro de 2012
Conclusão do estudo (Real)
1 de setembro de 2012
Datas de inscrição no estudo
Enviado pela primeira vez
30 de janeiro de 2014
Enviado pela primeira vez que atendeu aos critérios de CQ
31 de janeiro de 2014
Primeira postagem (Estimativa)
3 de fevereiro de 2014
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
3 de fevereiro de 2014
Última atualização enviada que atendeu aos critérios de controle de qualidade
31 de janeiro de 2014
Última verificação
1 de janeiro de 2014
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- AC-061-103
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