Empagliflozin Add on to Linagliptin Study in Japanese Patient With Type 2 Diabetes Mellitus
24 de setembro de 2018 atualizado por: Boehringer Ingelheim
A Phase III, Randomised, Double-blind, Parallel Group, 52 Week Study to Evaluate Efficacy and Safety of Once Daily Empagliflozin and Linagliptin Fixed Dose Combination Compared With Linagliptin Plus Placebo in Japanese Type 2 Diabetes Mellitus Patients With Insufficient Glycaemic Control After 16 Weeks Treatment With Once Daily Linagliptin 5 mg.
This trial will compare the use of fixed dose combination of empagliflozin and linagliptin to linagliptin alone in patient with type 2 diabetes mellitus
Visão geral do estudo
Status
Concluído
Condições
Tipo de estudo
Intervencional
Inscrição (Real)
275
Estágio
- Fase 3
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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Aichi, Nagoya, Japão, 454-0933
- Nagoya Kyoritsu Hospital
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Chiba, Kashiwa, Japão, 277-0825
- Kashiwa City Hospital
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Fukuoka, Fukuoka, Japão, 811-1346
- Otabe internal medicine clinic
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Fukuoka, Itoshima, Japão, 819-1104
- Nakamura Cardiovascular Clinic
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Fukuoka, Kurume, Japão, 830-0023
- Tanaka I.M. Clinic, Fukuoka, I.M.
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Fukushima, Koriyama, Japão, 963-8851
- Seino I.M. Clinic, Fukushima, I.M.
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Hiroshima, Hiroshima, Japão, 733-0011
- Hiraoka Naika Clinic, Hiroshima, I.M.
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Hokkaido, Sapporo, Japão, 003-0026
- Matsuda Cardiovascular Clinic
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Hokkaido, Sapporo, Japão, 006-0811
- Teine Keijinkai Clinic
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Hokkaido, Sapporo, Japão, 006-0852
- Mita Internal Medicine Cardiology Clinic
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Hokkaido, Sapporo, Japão, 063-0826
- Miyanosawa Clinic of Internal Medicine and Cardiology
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Ibaraki, Koga, Japão, 306-0232
- Itabashi Diabetic medicine and Dermatology Clinic
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Ibaraki, Naka, Japão, 311-0113
- Nakakinen clinic
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Kanagawa, Kawasaki, Japão, 214-0014
- Kubota Clinic
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Kanagawa, Sagamihara, Japão, 252-0375
- Kitasato University Hospital
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Kanagawa, Yokohama, Japão, 235-0045
- H.E.C Science Clinic
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Kyoto, Kyoto, Japão, 604-8151
- Yoshimasa Diabetes & Endocrine Clinic
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Kyoto, Kyoto, Japão, 615-8125
- Medical Corporation Hayashi Katagihara Clinic
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Kyoto, Kyoto, Japão, 607-8062
- Rakuwakai Otowa Hospital
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Nagano, Matsumoto, Japão, 390-0848
- Miyamoto Naika Clinic, Nagano, I.M.
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Nagano, Matsumoto, Japão, 399-0036
- Gibo Hepatology Clinic, Nagano, Digestive Tract I.M.
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Osaka, Higashi-Osaka, Japão, 577-0803
- Takekawa Clinic, Osaka, I.M.
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Osaka, Osaka, Japão, 532-0003
- Medical Corporation Koseikai Fukuda Naika Clinic
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Osaka, Osaka, Japão, 532-0026
- Kinugawa Cardiovascular Internal Medicine clinic
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Osaka, Osaka, Japão, 536-0023
- Sato Hospital
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Osaka, Osaka, Japão, 555-0032
- Nakaoka Clinic
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Osaka, Suita, Japão, 565-0853
- OCROM Clinic
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Osaka, Takatsuki, Japão, 569-1123
- Miyauchi Medical Center
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Saitama, Hanno, Japão, 357-0024
- Medical Corporation Shinseikai Mashiba Clinic
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Saitama, Kawagoe, Japão, 350-0851
- Asano Clinic
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Saitama, Saitama, Japão, 336-0963
- Medical Corporation Fusa Shimizu Clinic Fusa
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Saitama, Tokorozawa, Japão, 359-1161
- Ogino Clinic
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Tokyo, Chiyoda-ku, Japão, 101-0047
- Kanda Clinic
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Tokyo, Chuo-ku, Japão, 103-0027
- Fukuwa Clinic
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Tokyo, Chuo-ku, Japão, 103-0027
- Tokyo-Eki Center-building Clinic
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Tokyo, Hachioji, Japão, 192-0046
- Myojin Tou Clinic
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Tokyo, Koto-ku, Japão, 136-0073
- Sawai Medical Clinic
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Tokyo, Meguro-ku, Japão, 153-0051
- Mishuku Hospital
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Tokyo, Shinagawa-ku, Japão, 140-8522
- Toshiba General Hospital
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Tokyo, Shinjuku-ku, Japão, 160-0022
- ToCROM Clinic
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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
20 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion criteria:
- Diagnosis of Type-2 Diabetes Mellitus (T2DM) prior to informed consent
Male and female patients on diet and exercise regimen for at least 12 weeks prior to informed consent who are:
- 1 drug-naïve, defined as no antidiabetic drugs for at least 12 weeks prior to informed consent, or
- 2 pre-treated with one oral antidiabetic drug (for sulfonylurea, with up to half of the maximum approved dose) on stable dosage for at least 12 weeks prior to informed consent (for thiazolidinedione, therapy has to be unchanged for at least 18 weeks prior to the informed consent, for linagliptin 5 mg at least 16 weeks prior to Visit 1). Individual antidiabetic drug (except linagliptin) will have to be discontinued at Visit 1.
HbA1c at Visit 1
- 1 HbA1c =8.0% and =10.5% for patients who are drug-naïve, or
- 2 HbA1c =7.5% and =10.5% for patients with one oral antidiabetic drug (except linagliptin), or
- 3 HbA1c =7.5% and =10.0% for patients with linagliptin 5 mg
- HbA1c =7.5% and =10.0% at Visit 4 for randomisation into the double-blind treatment period. Patient who are pre-treated with linagliptin 5 mg for 16 weeks or more prior to Visit 1 and meet the criteria of HbA1c can directly move on to the run-in (Visit 4).
- Age =20 years at informed consent
- BMI =40.0 kg/m2 at Visit 1 (screening)
- Signed and dated written informed consent by date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation
Exclusion criteria:
- Uncontrolled hyperglycemia with a glucose level >270 mg/dL (>15.0 mmol/L) after an overnight fast during the open-label stabilisation period (from Visit 2 to Visit 4) and run-in period (from Visit 4 to Visit 5) , confirmed by a second measurement (not on the same day and done either at the central or at local laboratory).
- Acute coronary syndrome (ST-elevation myocardial infarction [STEMI], non-STEMI, and unstable angina pectoris), stroke or transient ischemic attack within 12 weeks prior to informed consent
- Indication of liver disease, defined by serum levels of either alanine aminotransferase (ALT Serum glutamic pyruvate transaminase [SGPT]), aspartate aminotransferase (AST, Serum glutamic oxaloacetic transaminase [SGOT]), or alkaline phosphatase (ALP) above 3 x upper limit of normal (ULN) as determined during screening, open-label stabilisation period and/or run-in period
- Impaired renal function, defined as estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 (MDRD formula) as determined during screening, open-label stabilisation period and/or run-in period
- Known hereditary galactose intolerance
- Known contraindications to linagliptin and empagliflozin according to the Japanese label
- Any previous (within 2 years prior to informed consent) or planned bariatric surgery (or any other weight loss surgery) or other gastrointestinal surgery that induce chronic malabsorption
- Medical history of cancer (except for resected non-invasive basal cell or squamous carcinoma) and/or treatment for cancer within the last 5 years
- Known blood dyscrasias or any disorders causing haemolysis or unstable red blood cell (RBC) count (e.g. malaria, babesiosis, haemolytic anaemia).
- Treatment with insulin, Glucagon-like peptide-1 agonists, within 12 weeks prior to informed consent
- Treatment with anti-obesity drugs within 12 weeks prior to informed consent or any other treatment at the time of screening (i.e., surgery, aggressive diet regimen, etc.) leading to unstable body weight
- Current treatment with systemic steroids (other than inhaled or topical steroids) at informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM
Pre-menopausal women (last menstruation =1 year prior to informed consent) who:
- 1 are nursing or pregnant or
- 2 are of child-bearing potential and are not practicing an acceptable method of birth control, or do not plan to continue using this method throughout the trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable methods of birth control include tubal ligation, intra uterine devices/systems, oral contraceptives, complete sexual abstinence, double barrier method and vasectomised partner
- Known or suspected allergy or hypersensitivity to trial products or related products (e.g., Dipeptidyl-peptidase-4 inhibitors or Sodium-glucose co-transporter-2 inhibitors)
- Alcohol or drug abuse within the 12 weeks prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to trial procedures or trial drug intake, by the judgment of the investigator
- Intake of an investigational drug in another trial within 30 days prior to Visit 1 or participation in the follow-up period of another trial (participation in observational studies is permitted)
- Any other clinical condition that, in the opinion of the investigator, would jeopardize patient's safety while participating in this clinical trial
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: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Comparador Ativo: Linagliptin
patient to receive 5 mg linagliptin once daily
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Outros nomes:
Matching placebo empagliflozin + linagliptin
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Experimental: Empagliflozin + linagliptin low dose
patient to receive one tablet once daily
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tablet
Matching placebo linagliptin
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Experimental: Empagliflozin + linagliptin high dose
patient to receive one tablet once daily
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Matching placebo linagliptin
tablet
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Comparador de Placebo: Linagliptin placebo
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tablet
Matching placebo linagliptin
tablet
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Comparador de Placebo: Empagliflozin + linagliptin high dose placebo
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Outros nomes:
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Comparador de Placebo: Empagliflozin + linagliptin low dose placebo
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Outros nomes:
Matching placebo empagliflozin + linagliptin
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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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Change of Glycosylated Haemoglobin A1c (Glycosylated Haemoglobin A1c After 24 Weeks of Double-blind Treatment From Baseline)
Prazo: Baseline and 24 week
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Change from baseline in Glycosylated haemoglobin A1c (HbA1c) at Week 24 was calculated as: HbA1c at Week 24 - HbA1c at baseline.
Baseline is referred to the last observed measurement prior to the administration of randomized trial medication.
Adjusted mean (Least square mean) and its standard error (SE) is presented.
|
Baseline and 24 week
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change in HbA1c From Week 28 at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Only)
Prazo: 28 Week (pre up-titration) and 52 Week
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Change from Week 28 in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at Week 28. Week 28 (pre up-titration) is referred to the last observed measurement prior to the first administration of any double-blind randomized trial medication in the up-titration period. Adjusted mean (Least square mean) and its standard error (SE) is presented. This endpoint was based on 1 group of the Full analysis set with up-titration (FASUT-II) whose dose was up-titrated to Empagliflozin 25 mg/Linagliptin 5 mg fixed dose combination thus there is no comparison group. Hence, no comparison is made. A restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) approach was used with baseline HbA1c as linear covariate and baseline eGFR, prior use of antidiabetic drug, visit as fixed effect(s). The covariance used to fit the model was unstructured. |
28 Week (pre up-titration) and 52 Week
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Change in HbA1c From Baseline at Week 52 (All Empagliflozin Versus All Placebo)
Prazo: Baseline and 52 week
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Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at baseline.
Baseline is referred to the last observed measurement prior to the administration of randomized trial medication.
Adjusted mean (Least square mean) and its standard error (SE) is presented.
|
Baseline and 52 week
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Change in HbA1c From Baseline at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Versus Linagliptin 5 mg + Placebo 25 mg)
Prazo: Baseline and 52 week
|
Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at baseline.
Baseline is referred to the last observed measurement prior to the administration of randomized trial medication.
Adjusted mean (Least square mean) and its standard error (SE) is presented.
|
Baseline and 52 week
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Change in HbA1c From Baseline at Week 52 (Empagliflozin 25 mg/Linagliptin 5 mg Versus All Placebo)
Prazo: Baseline and 52 week
|
Change from baseline in HbA1c at Week 52 was calculated as: HbA1c at Week 52 - HbA1c at baseline.
Baseline is referred to the last observed measurement prior to the administration of randomized trial medication.
Adjusted mean (Least square mean) and its standard error (SE) is presented.
|
Baseline and 52 week
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Colaboradores
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)
14 de maio de 2015
Conclusão Primária (Real)
26 de agosto de 2016
Conclusão do estudo (Real)
27 de março de 2017
Datas de inscrição no estudo
Enviado pela primeira vez
21 de maio de 2015
Enviado pela primeira vez que atendeu aos critérios de CQ
21 de maio de 2015
Primeira postagem (Estimativa)
25 de maio de 2015
Atualizações de registro de estudo
Última Atualização Postada (Real)
15 de fevereiro de 2019
Última atualização enviada que atendeu aos critérios de controle de qualidade
24 de setembro de 2018
Última verificação
1 de setembro de 2018
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Distúrbios do Metabolismo da Glicose
- Doenças Metabólicas
- Doenças do Sistema Endócrino
- Diabetes Mellitus
- Diabetes Mellitus, Tipo 2
- Hipoglicemiantes
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Inibidores Enzimáticos
- Hormônios
- Hormônios, Substitutos Hormonais e Antagonistas Hormonais
- Inibidores de Protease
- Incretinas
- Inibidores do transportador de sódio-glicose 2
- Inibidores de Dipeptidil-Peptidase IV
- Empagliflozina
- Linagliptina
Outros números de identificação do estudo
- 1275.19
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 .