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- Ensaio Clínico NCT00840320
Repeat Dose Safety Study for Compound to Treat Anemia
21 de junho de 2017 atualizado por: GlaxoSmithKline
A Phase I, Randomized, Single-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Repeat Oral Doses of 1278863A in Healthy Subjects
The purpose of this study is to characterize the safety and tolerability of repeat doses of compound 1278863A in healthy subjects.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Descrição detalhada
Compound 1278863A is a novel small molecule agent, which stimulates erythropoiesis through inhibition of hypoxia-inducible factor (HIF)-prolyl hydroxylases (EGLNs).
This compound is being developed for the treatment of anemia.
Compound 111427 was the first administration of compound 1278863A to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses up to 300 mg in healthy adult subjects.
This study, PHI112842, will be the first administration of compound 1278863A to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of repeat oral doses up to 300 mg for 14 days in healthy adult subjects.
At least 6 subjects will complete each cohort.
Multiple blood samples for pharmacokinetic analyses will be obtained post-dose in each cohort.
Safety will be assessed by measurement of vital signs, cardiac monitoring, collection of adverse event assessments and laboratory safety tests.
Blood samples will be collected for pharmacodynamic analyses.
Tipo de estudo
Intervencional
Inscrição (Real)
24
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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Victoria
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Melbourne, Victoria, Austrália, 3004
- GSK Investigational Site
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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 55 anos (Adulto)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- Male or female between 18 and 55 years of age, inclusive.
- A female subject must be of non-childbearing potential.
- Male subjects must agree to use one of the acceptable contraception methods listed in the protocol
- Body weight greater than or equal to 50 kg and BMI within the range 19 - 31 kg/m2 (inclusive).
- Capable of giving written informed consent
- QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.
Exclusion Criteria:
- The subject has a positive pre-study drug screen.
A hemoglobin value at screening is:
- Male subjects or post-menopausal females: > 15.5 g/dL
- Female subjects: > 14.5 g/dL
The values of hematological parameters at screening are:
MCV: outside the reference range and clinically significant deemed by the investigator and GSK Medical Monitor
The values of the following tests at screening are:
- TIBC: outside the reference range
- Serum iron: outside the reference range
- Serum ferritin: outside the reference range
- A value at screening is greater than the upper limit of reference range for the following clinical laboratory parameters: AST, ALT, direct bilirubin.
- Clinically significant abnormal CPK determined by the investigator and GSK Medical Monitor.
- Calculated creatinine clearance: < 60mL/min
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- A positive test for HIV antibody.
- History of drug abuse or dependence within 6 months of the study.
- History of regular alcohol consumption within 6 months of the study
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study drug
- History of sensitivity to any of the study drugs, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- History of sensitivity to heparin or heparin-induced thrombocytopenia. (if the clinical research unit uses heparin to maintain intravenous cannula patency)
- Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function that could interfere with the absorption, metabolism, and/or excretion of the study drugs.
- History of peptic ulcer disease.
- History of malignancy tumor. Non-melanoma skin cancer that has been definitely removed is allowed.
- Pregnant females as determined by positive serum or urine hCG test at screening or prior to dosing.
- Lactating females.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Unwillingness or inability to follow the procedures, or lifestyle and/or dietary restrictions outlined in the protocol.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice, exotic citrus fruits, grapefruit hybrids or fruit juices of the prohibited fruits from 7 days prior to the first dose of study medication
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Subject is mentally or legally incapacitated.
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: Ciência básica
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
---|---|
Experimental: 1
Repeat doses of active at escalating doses
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15mg, 25mg, 50mg, 150mg
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Comparador de Placebo: 2
Repeat doses of placebo
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placebo correspondente
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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adverse events reporting
Prazo: throughout study
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throughout study
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Safety Labs (hematology)
Prazo: Screening, Days -1, 1-3, 5, 7, 9, 11, 14-18, 21, 25, 28
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Screening, Days -1, 1-3, 5, 7, 9, 11, 14-18, 21, 25, 28
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vital signs (blood pressure and heart rate)
Prazo: Days 1-15, 28
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Days 1-15, 28
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12-lead ECG
Prazo: Screening, Days 1-2, 4, 6, 8, 10, 12, 14, 28
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Screening, Days 1-2, 4, 6, 8, 10, 12, 14, 28
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dual-lead cardiac monitoring (telemetry monitoring)
Prazo: Days -1 to 3, 14
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Days -1 to 3, 14
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clinical monitoring/observation
Prazo: throughout
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throughout
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Safety Labs (Chemistry)
Prazo: Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
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Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
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Safety Labs (Urinalysis)
Prazo: Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
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Screening, Days -1, 1-3, 7, 10, 14-15, 17, 21, 28
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Medidas de resultados secundários
Medida de resultado |
Prazo |
---|---|
AUC(0-∞) on Day 1, AUC(0-τ), Cmax, tmax and t1/2, on Days 1 and 14
Prazo: Days 1-2, 4, 6, 8, 10, 12, 14-18
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Days 1-2, 4, 6, 8, 10, 12, 14-18
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Trough plasma concentrations at the end of the dosing interval
Prazo: Days 2, 4, 6, 8, 10 and 12
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Days 2, 4, 6, 8, 10 and 12
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Hemoglobin actual values, rate of rise, maximum change from baseline, and rate of decline following stopping of dosing
Prazo: Days 1, 7, 14, 21, 28
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Days 1, 7, 14, 21, 28
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Fetal hemoglobin actual values, change from baseline, and percent of total hemoglobin
Prazo: Days 1, 7, 14, 21, 28
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Days 1, 7, 14, 21, 28
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Actual values and change from baseline in erythropoietin
Prazo: Days 1-4, 7, 14-15, 18, 21
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Days 1-4, 7, 14-15, 18, 21
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Actual values and change from baseline in absolute VEGF
Prazo: Days 1-2, 14-15, 18, 21
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Days 1-2, 14-15, 18, 21
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Actual values and change from baseline in hepcidin
Prazo: Days 1-2, 7, 14-15, 18, 21
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Days 1-2, 7, 14-15, 18, 21
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Actual values and change from baseline in total iron binding capacity (TIBC)
Prazo: Screening, Days 1, 7, 14, 18, 21
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Screening, Days 1, 7, 14, 18, 21
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Actual values and change from baseline in transferring saturation (%)
Prazo: Days 1, 7, 14, 18, 21
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Days 1, 7, 14, 18, 21
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
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)
13 de março de 2009
Conclusão Primária (Real)
2 de setembro de 2009
Conclusão do estudo (Real)
2 de setembro de 2009
Datas de inscrição no estudo
Enviado pela primeira vez
9 de fevereiro de 2009
Enviado pela primeira vez que atendeu aos critérios de CQ
9 de fevereiro de 2009
Primeira postagem (Estimativa)
10 de fevereiro de 2009
Atualizações de registro de estudo
Última Atualização Postada (Real)
22 de junho de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
21 de junho de 2017
Última verificação
1 de junho de 2017
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 112842
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 .