- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT00539760
A Phase I Rheumatoid Arthritis Study in Healthy Volunteers
11 de agosto de 2017 atualizado por: GlaxoSmithKline
A Phase I, Randomized, Observer- and Subject-Blind, Placebo-Controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK1827771 in Healthy Volunteers
GSK182771 is a domain antibody targeting the interleukin (IL)-1 receptor which is being developed for the treatment of rheumatoid arthritis.
This study is being done in healthy volunteers to verify the safety and tolerability of GSK182771
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
45
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
-
-
Indiana
-
Evansville, Indiana, Estados Unidos, 47714
- GSK Investigational Site
-
-
Maryland
-
Baltimore, Maryland, Estados Unidos, 21225
- GSK Investigational Site
-
-
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
Sim
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- Healthy adult men or women as determined by a responsible physician, based on a medical evaluation including history, physical examination, laboratory tests and cardiac assessment.
- Female subjects of non-childbearing potential.
- Male subjects must agree to abstain from or agree to use adequate contraception, in addition to having their female partner use another form of contraception. This criterion must be followed from the time of the first dose of study medication until Pharmacokinetic levels are determined to be below the LLQ.
- Men or women who are between 18 and 55 years of age, inclusive.
- Body Mass Index (BMI) within the range of 18-35 kilogram per meter square (kg/m^2) inclusive.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
Exclusion Criteria:
- The subject has a positive pre-study urine drug/urine alcohol screen. A minimum list of drugs that will be screened for includes amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- A history of regular alcohol consumption averaging >7 drinks/week for females or >14 drinks/week for males. One drink is equivalent to (12 g alcohol) = 5 ounces [150 milliliter (mL)] of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits
- The subject is unwilling to abstain from alcohol consumption from 48 hour prior to dosing until discharge from the clinic, and for 48 hour prior to all other out-patient clinic visits.
- Smoked or used tobacco or nicotine-containing products within the previous 6 months prior to the first dose of current study medication.
- The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
- Previous exposure to or treatment with PEGylated molecules.
- Use of anti-Tumor Necrosis Factor (anti-TNF) drugs within 60 days prior to dosing.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days , or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy (including antibiotics) which, in the opinion of the investigator and/or GSK Medical Monitor, contraindicates the subject's participation.
- Positive pregnancy test at Screening or on Day -1 (females only).
- Any clinically significant abnormality identified on the screening medical assessment or examination, or ECG.
- Any white blood cell (WBC) or neutrophil count outside the normal range at screening or on Day -1.
- History of significant cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal conditions that in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as participant in this trial.
- History of any autoimmune or current inflammatory conditions including rheumatoid arthritis or any other joint disease.
- History of malignancy, except for surgically cured basal cell carcinoma or cured cervical carcinoma (> 2 yrs prior to dosing).
- Currently has asthma or history of chronic obstructive pulmonary disease (COPD).
- Current evidence of ongoing or acute infection.
- The subject has a history of repeated, chronic or opportunistic infections which, in the opinion of the investigator and/or GSK Medical Monitor, places the subject at an unacceptable risk as a participant in this trial.
- History of Mycobacterium tuberculosis or any other previous Mycobacterium infection.
- A positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody testing result.
- History of a severe allergic reaction, angio-edema, anaphylaxis or immunodeficiency
- History of elevated blood pressure or blood pressure >140/90 millimeters of mercury (mmHg) at screening.
- Corrected QT interval (QTc) > 450 milliseconds.
- Where participation in study would result in donation of blood in excess of 500 mL within 56 days of starting the study.
- Subject whose calculated creatinine clearance is less than 80 mL/min
- Liver function tests above the upper limit of normal at screening (alkaline transaminase (ALT), aspartate transaminase (AST) or bilirubin).
- Chronic liver or biliary disease, history of Gilbert's syndrome in a previous clinical study or at screening.
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: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
---|---|
Experimental: Subjects receiving GSK 1827771 in sub-cohort Xa (Cohort 1-5)
Eligible subjects will receive GSK1827771 with the starting dose of 0.3 milligram (mg)
|
GSK1827771 will be administered using injection via subcutaneous (SC) route.
|
Comparador de Placebo: Subjects receiving placebo in sub-cohort Xa (Cohort 1-5)
Eligible subjects will receive placebo matching to GSK1827771
|
Placebo to GSK1827771 for Injection will be administered via SC route
|
Experimental: Subjects receiving GSK 1827771 in sub-cohort Xb (Cohort 1-5)
Eligible subjects will receive GSK1827771 via injection
|
GSK1827771 will be administered using injection via subcutaneous (SC) route.
|
Comparador de Placebo: Subjects receiving placebo in sub-cohort Xb (Cohort 1-5)
Eligible subjects will receive placebo matching to GSK1827771
|
Placebo to GSK1827771 for Injection will be administered via SC route
|
Experimental: Subjects receiving GSK 1827771 in sub-cohort Xc (Cohort 1-5)
Eligible subjects will receive GSK1827771 via injection
|
GSK1827771 will be administered using injection via subcutaneous (SC) route.
|
Comparador de Placebo: Subjects receiving placebo in sub-cohort Xc (Cohort 1-5)
Eligible subjects will receive placebo matching to GSK1827771
|
Placebo to GSK1827771 for Injection will be administered via SC route
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Number of subjects with abnormal clinical chemistry findings
Prazo: Up to 29 days
|
Blood samples will be collected at specific time points as a measure of safety
|
Up to 29 days
|
Number of subjects with abnormal clinical hematology findings
Prazo: Up to 29 days
|
Blood samples will be collected at specific time points as a measure of safety
|
Up to 29 days
|
Number of subjects with abnormal urinalysis findings
Prazo: Up to 29 days
|
Urine samples will be collected at specific time points as a measure of safety
|
Up to 29 days
|
Number of subjects with abnormal blood pressure values
Prazo: Up to 29 days
|
Systolic and diastolic blood pressure will be measured in a supine position after at least 5 minutes of rest as a measure of safety.
|
Up to 29 days
|
Number of subjects with abnormal heart rate values
Prazo: Up to 29 days
|
Heart rate will be measured in a supine position after at least 5 minutes of rest as a measure of safety.
|
Up to 29 days
|
Number of subjects with abnormal respiratory rate values
Prazo: Up to 29 days
|
Respiratory rate will be measured in a supine position after at least 5 minutes of rest as a measure of safety.
|
Up to 29 days
|
Number of subjects with abnormal body temperature findings
Prazo: Up to 29 days
|
Body temperature will be measured in a supine position after at least 5 minutes of rest as a measure of safety.
|
Up to 29 days
|
Number of subjects with abnormal electrocardiogram (ECG) findings
Prazo: Up to 29 days
|
12-lead ECG measurements will be performed in a supine position after at least 5 minutes of rest as a measure of safety
|
Up to 29 days
|
Number of subjects with adverse events (AEs)
Prazo: Up to 29 days
|
An adverse event is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
|
Up to 29 days
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
---|---|---|
Plasma concentrations of GSK1827771
Prazo: Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
|
Blood samples will be collected at specific time points for calculating plasma concentrations of GSK1827771
|
Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
|
Maximum plasma concentration (Cmax) of GSK1827771
Prazo: Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
|
Blood samples will be collected at specific time points for calculating Cmax of GSK1827771
|
Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
|
Area under the curve (AUC) of GSK1827771
Prazo: Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
|
Blood samples will be collected at specific time points for calculating AUC of GSK1827771
|
Pre-dose, 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dose on Day 1; in morning and evening on Day 2-7; in morning on Day 14, 21, 28
|
Frequency of anti-GSK1827771
Prazo: Up to 29 days
|
The presence of anti-GSK1827771 binding antibodies will be assessed using an immunoelectrochemiluminescence screening assay (ECL).
|
Up to 29 days
|
Titer of anti-GSK1827771
Prazo: Up to 29 days
|
Blood samples for determination of anti-GSK1827771 antibodies will be taken at specific time points.
|
Up to 29 days
|
Frequency of anti-PEG
Prazo: Up to 29 days
|
Antibodies to PEG components of GSK1827771 will be measured.
|
Up to 29 days
|
Titer of anti-PEG
Prazo: Up to 29 days
|
Antibodies to PEG components of GSK1827771 will be measured.
|
Up to 29 days
|
Frequency of anti-dAb
Prazo: Up to 29 days
|
Antibodies to dAb components of GSK1827771 will be measured.
|
Up to 29 days
|
Titer of anti-dAb
Prazo: Up to 29 days
|
Antibodies to dAb components of GSK1827771 will be measured.
|
Up to 29 days
|
Change from Baseline response of whole blood to ex vivo stimulation with IL-1 alpha or IL-1 beta
Prazo: Baseline and up to 29 days
|
Blood samples will be collected for assessment of pharmacodynamic activity of GSK1827771 at specific time points
|
Baseline and up to 29 days
|
Exploratory biomarker levels in blood
Prazo: Up to 29 days
|
Blood samples will be taken for exploratory biomarker analysis
|
Up to 29 days
|
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)
5 de setembro de 2007
Conclusão Primária (Real)
5 de abril de 2008
Conclusão do estudo (Real)
5 de abril de 2008
Datas de inscrição no estudo
Enviado pela primeira vez
4 de outubro de 2007
Enviado pela primeira vez que atendeu aos critérios de CQ
4 de outubro de 2007
Primeira postagem (Estimativa)
5 de outubro de 2007
Atualizações de registro de estudo
Última Atualização Postada (Real)
15 de agosto de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
11 de agosto de 2017
Última verificação
1 de agosto de 2017
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 110394
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 .