- ICH GCP
- Registro de ensaios clínicos dos EUA
- Ensaio Clínico NCT01045590
Glibenclamide (Dose to be Titrated From Starting Dose of 5mg om) Plus Rosiglitazone 4mg om (Increased to 8mg om After 6 Months) and vs Glibenclamide (Dose to be Titrated With Starting Dose of 5mg om) Plus Placebo, Administered to Patients With Type 2 Diabetes Mellitus
Phase IV, Multicenter, Single-blind, Positive-controlled, Parallel Group Study of Glibenclamide (Dose to be Titrated From Starting Dose of 5mg om) Plus Rosiglitazone 4mg om (Increased to 8mg om After 6 Months) and vs Glibenclamide (Dose to be Titrated With Starting Dose of 5mg om) Plus Placebo, Adm
Rationale Rosiglitazone and troglitazone both promote differentiation of pre-adipocytes into adipocytes in subcutaneous, but not omental fat, and reduce gamma glutamyl transferase, a surrogate marker for intra-abdominal and hepatic fat. Troglitazone has been shown by abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scan to reduce the intra-abdominal adipose tissue area in type 2 diabetics. Similarly rosiglitazone has also been shown to increase subcutaneous but not intra-abdominal fat in patients with type 2 diabetes. In the same study it was also shown to cause a substantial reduction in hepatic fat. Central fat depots are believed to be associated with more cardiovascular risk than subcutaneous fat depots. By contrast, sulphonylurea-associated weight gain has been shown by abdominal CT scan to include increases in intra-abdominal adipose tissue.
The aim of this study is to compare the body fat distribution pattern of glibenclamide plus rosiglitazone versus glibenclamide and placebo (especially the intra-abdominal adipose tissue and abdominal subcutaneous adipose tissue areas) in patients with type 2 diabetes. It is hypothesised that rosiglitazone will lead to the accumulation of excess energy stores in the subcutaneous rather than the intra-abdominal adipose tissue depot. In addition, it is hoped that by having a positive effect on diastolic blood pressure, lipid levels, BMI, rosiglitazone will be shown to have a better cardiovascular risk profile when used in combination with glibenclamide rather than when glibenclamide is used alone.
Although insulin resistance has been shown to be a primary defect causing type 2 diabetes mellitus, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes mellitus. A previous study has shown that in Korean patients, early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes mellitus [56].
This study also aims to assess the efficacy and safety of glibenclamide plus rosiglitazone versus glibenclamide plus placebo therapy in Korean patients with type 2 diabetes. In addition, a previous study has shown that in Korean patients, early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes mellitus. This study aims to show that rosiglitazone treatment in Korean patients, regardless of their early phase insulin secretory ability, is just as efficacious and safe.
Objective(s) Primary To evaluate the effect of 12 months oral treatment with glibenclamide plus rosiglitazone versus oral glibenclamide plus placebo, on body fat distribution (as measured by the change in the ratio between the intra-abdominal adipose tissue and abdominal subcutaneous adipose tissue areas) in patients with type 2 diabetes.
Secondary
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on beta-cell function and insulin resistance as calculated by HOMA-B and HOMA-R.
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on fasting plasma glucose, insulin, fasting serum lipid profile (total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol and total cholesterol to HDL cholesterol ratio).
- To investigate the efficacy of glibenclamide plus rosiglitazone, compared to glibenclamide plus placebo on early phase insulin secretion during an oral glucose tolerance test as measured by the insulinogenic index.
- To define further the clinical safety and tolerability of glibenclamide plus rosiglitazone through the assessment of physical examinations, vital signs, weight, routine laboratory tests, adverse experiences and electrocardiograms (ECGs).
Endpoint(s) Primary Change from baseline in the ratio (IAAT:SAT) between the intra-abdominal adipose tissue area (IAAT) and abdominal subcutaneous adipose tissue area [SAT] after 12 months treatment with oral glibenclamide plus rosiglitazone compared to oral glibenclamide plus placebo Secondary
Comparisons will be made between glibenclamide plus rosiglitazone and glibenclamide plus placebo treatment groups on Change from baseline after 6 and 12 months treatment with respect the following:
CT Scan
Derived from CT image at the lumbar IV level:
- abdominal subcutaneous adipose tissue area [SAT]
- intra-abdominal adipose tissue area [IAAT]
Derived from the CT image of the right leg at the thigh level (1cm below the gluteal fold):
- total subcutaneous adipose tissue area [TSAT] Derived from CT images at the lumbar IV and thigh level
- ratio between abdominal subcutaneous adipose tissue area [SAT] and total subcutaneous adipose tissue area of the thigh [TSAT]
- ratio between intra-abdominal adipose tissue area [IAAT] and total subcutaneous adipose tissue area of the thigh [TSAT] Derived from Oral Glucose Tolerance Test, glycaemic response to OGTT, difference
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 4
Contactos e Locais
Locais de estudo
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Seoul, Republica da Coréia, 120-752
- GSK Investigational Site
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Seoul, Republica da Coréia, 137-701
- GSK Investigational Site
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Seoul, Republica da Coréia, 110-744
- GSK Investigational Site
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Seoul, Republica da Coréia, 135-710
- GSK Investigational Site
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Subjects were selected by following considerations:
- Diagnosis of type 2 diabetes mellitus defined by the American Diabetic Association (ADA) criteria.
- Subject whose diabetes was managed by diet, exercise, and/or sulfonylurea, and/or metformin, who could be converted to treatment with glibenclamide 5mg om.
- 126mg/dL ≤ fasting plasma glucose (FPG) ≤ 270mg/dL and HbA1c level >7% at screening. In addition, the following criterion was applied prior to randomization: 126mg/dL ≤ fasting plasma glucose (FPG) ≤ 270mg/dL at baseline(after 2 months of run-in treatment with glibenclamide 5mg om only).
Plano de estudo
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 |
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Comparador Ativo: glibenclamide + Rosiglitazone
glibenclamide plus rosiglitazone
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Patients in the glibenclamide plus placebo treatment group Patients in the glibenclamide plus placebo treatment group who have FPG < 270mg/dL after the glibenclamide 5mg om run-in will continue to receive glibenclamide 5mg om.
At every subsequent visit, the glibenclamide dose will be titrated to achieve the target HbA1c level of < 7%.
If the HbA1c is > 7%, the dose of glibenclamide will be escalated in the following sequence: from 5mg om, to 5mg om, 2.5mg on, to 5mg bd and 7.5mg om, 5mg on, to 7.5mg bd.
The maximum total daily dose will not exceed 15 mg.
A downward titration of glibenclamide using the above sequence in the reverse order can be used to maintain normoglycemia at any visit.
Once the target HbA1c level of < 7% is achieved, the dose of glibenclamide is maintained.
If at the glibenclamide dose of 7.5mg bd, the HbA1c is > 7% for 2 subsequent visits, the patient will be withdrawn from the study.
Patients in the glibenclamide + rosiglitazone treatment group who have FPG < 270mg/dL after the glibenclamide 5mg om run-in will receive glibenclamide 5mg om + rosiglitazone 4mg om.
At every subsequent visit, the glibenclamide dose will be titrated to achieve the target HbA1c level of < 7%.
If the HbA1c is > 7%, the dose of glibenclamide will be escalated in a similar fashion as above.
The only exception is at visit 5 when the dose of rosiglitazone is increased (see next paragraph).
Once the target HbA1c level of < 7% is achieved, the dose of glibenclamide is maintained.
If at the glibenclamide dose of 7.5mg bd, the HbA1c is > 7% for 2 subsequent visits, the patient will be withdrawn from the study.
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Comparador de Placebo: glibenclamide + placebo
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Patients in the glibenclamide plus placebo treatment group Patients in the glibenclamide plus placebo treatment group who have FPG < 270mg/dL after the glibenclamide 5mg om run-in will continue to receive glibenclamide 5mg om.
At every subsequent visit, the glibenclamide dose will be titrated to achieve the target HbA1c level of < 7%.
If the HbA1c is > 7%, the dose of glibenclamide will be escalated in the following sequence: from 5mg om, to 5mg om, 2.5mg on, to 5mg bd and 7.5mg om, 5mg on, to 7.5mg bd.
The maximum total daily dose will not exceed 15 mg.
A downward titration of glibenclamide using the above sequence in the reverse order can be used to maintain normoglycemia at any visit.
Once the target HbA1c level of < 7% is achieved, the dose of glibenclamide is maintained.
If at the glibenclamide dose of 7.5mg bd, the HbA1c is > 7% for 2 subsequent visits, the patient will be withdrawn from the study.
Patients in the glibenclamide + rosiglitazone treatment group who have FPG < 270mg/dL after the glibenclamide 5mg om run-in will receive glibenclamide 5mg om + rosiglitazone 4mg om.
At every subsequent visit, the glibenclamide dose will be titrated to achieve the target HbA1c level of < 7%.
If the HbA1c is > 7%, the dose of glibenclamide will be escalated in a similar fashion as above.
The only exception is at visit 5 when the dose of rosiglitazone is increased (see next paragraph).
Once the target HbA1c level of < 7% is achieved, the dose of glibenclamide is maintained.
If at the glibenclamide dose of 7.5mg bd, the HbA1c is > 7% for 2 subsequent visits, the patient will be withdrawn from the study.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Prazo |
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Change from baseline in the ratio (IAAT:SAT) between the intra-abdominal adipose tissue area (IAAT) and abdominal subcutaneous adipose tissue area [SAT] after 12 months treatment with oral glibenclamide plus rosiglitazone compared to oral glibenclamide p
Prazo: baseline
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baseline
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Medidas de resultados secundários
Medida de resultado |
Prazo |
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Comparisons will be made between glibenclamide plus rosiglitazone and glibenclamide plus placebo treatment groups on Change from baseline after 6 and 12 months treatment with respect the following
Prazo: baseline
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baseline
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Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 100684
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Ensaios clínicos em titration
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Hospital Galdakao-UsansoloCarlos III Health Institute; Basque Health ServiceConcluído