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Efficacy and Safety of Azilsartan Medoxomil Used in Combination With Metformin in Participants With Hypertension and Diabetes

20 de abril de 2015 atualizado por: Takeda

A Randomized, Double-Blind, Phase 3b Proof-of-Concept Study to Evaluate the Efficacy and Safety of TAK-491 Compared to Placebo When Used in Combination With Metformin in Subjects With Hypertension and Type 2 Diabetes

The purpose of this study was to evaluate the antihypertensive and antiglycemic effects, as well as the safety and tolerability of TAK-491 (azilsartan medoxomil), once daily (QD), in stage 1 hypertensive, type 2 diabetes mellitus (T2DM) participants whose glycemic control was inadequate on metformin alone.

Visão geral do estudo

Status

Rescindido

Condições

Intervenção / Tratamento

Descrição detalhada

The study included a Screening Period of up to 4 weeks, which coincided with a 2-week single-blind, placebo Run-in Period, a 24 week Treatment Period, and a 2-week Follow-up Period. The duration of the study was approximately 30 weeks. The planned number of participants (n=450) was not reached; actual enrollment consisted of 105 particpants. Due to low enrollment this study was terminated early by Takeda.

Tipo de estudo

Intervencional

Inscrição (Real)

105

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

  • Estados Unidos
    • Alabama
      • Birmingham, Alabama, Estados Unidos
    • Arizona
      • Green Valley, Arizona, Estados Unidos
      • Tempe, Arizona, Estados Unidos
      • Tucson, Arizona, Estados Unidos
    • California
      • Buena Park, California, Estados Unidos
      • Hawaiian Gardens, California, Estados Unidos
      • Norwalk, California, Estados Unidos
      • Paramount, California, Estados Unidos
      • Rancho Cucamonga, California, Estados Unidos
      • Sacramento, California, Estados Unidos
      • San Diego, California, Estados Unidos
      • Tustin, California, Estados Unidos
    • Colorado
      • Denver, Colorado, Estados Unidos
    • Florida
      • Bradenton, Florida, Estados Unidos
      • Brooksville, Florida, Estados Unidos
      • Hallandale Beach, Florida, Estados Unidos
      • Jupiter, Florida, Estados Unidos
      • Miami, Florida, Estados Unidos
      • Orlando, Florida, Estados Unidos
      • Pembroke Pines, Florida, Estados Unidos
      • St Petersburg, Florida, Estados Unidos
      • Tampa, Florida, Estados Unidos
      • Winter Park, Florida, Estados Unidos
    • Georgia
      • Roswell, Georgia, Estados Unidos
    • Illinois
      • Chicago, Illinois, Estados Unidos
      • Evergreen Park, Illinois, Estados Unidos
      • Gurnee, Illinois, Estados Unidos
    • Indiana
      • Avon, Indiana, Estados Unidos
      • Greenfield, Indiana, Estados Unidos
    • Kentucky
      • Lexington, Kentucky, Estados Unidos
      • Paducah, Kentucky, Estados Unidos
    • Maryland
      • Baltimore, Maryland, Estados Unidos
    • Missouri
      • Columbia, Missouri, Estados Unidos
    • Nebraska
      • Omaha, Nebraska, Estados Unidos
    • Nevada
      • Las Vegas, Nevada, Estados Unidos
    • New Jersey
      • Margate, New Jersey, Estados Unidos
    • New Mexico
      • Albuquerque, New Mexico, Estados Unidos
    • New York
      • Brooklyn, New York, Estados Unidos
    • North Carolina
      • Calabash, North Carolina, Estados Unidos
      • Greensboro, North Carolina, Estados Unidos
      • Lenoir, North Carolina, Estados Unidos
      • Morehead City, North Carolina, Estados Unidos
      • Salisbury, North Carolina, Estados Unidos
      • Wilmington, North Carolina, Estados Unidos
      • Winston-Salem, North Carolina, Estados Unidos
    • Ohio
      • Centerville, Ohio, Estados Unidos
      • Cincinnati, Ohio, Estados Unidos
    • Oklahoma
      • Oklahoma City, Oklahoma, Estados Unidos
    • Pennsylvania
      • Downingtown, Pennsylvania, Estados Unidos
      • Fleetwood, Pennsylvania, Estados Unidos
      • Reading, Pennsylvania, Estados Unidos
    • Rhode Island
      • Providence, Rhode Island, Estados Unidos
    • South Carolina
      • Anderson, South Carolina, Estados Unidos
    • Tennessee
      • Chattanooga, Tennessee, Estados Unidos
      • Kingsport, Tennessee, Estados Unidos
      • Nashville, Tennessee, Estados Unidos
    • Texas
      • Dallas, Texas, Estados Unidos
      • Houston, Texas, Estados Unidos
      • Irving, Texas, Estados Unidos
      • North Richland Hills, Texas, Estados Unidos
      • Pearland, Texas, Estados Unidos
      • San Antonio, Texas, Estados Unidos
    • Utah
      • Salt Lake City, Utah, Estados Unidos
    • Virginia
      • Burke, Virginia, Estados Unidos
      • Manassas, Virginia, Estados Unidos
      • Richmond, Virginia, Estados Unidos
      • Virginia Beach, Virginia, Estados Unidos
    • Wisconsin
      • Wauwatosa, Wisconsin, Estados Unidos

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 e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

Inclusion Criteria:

  1. Was male or female and ≥18 years.
  2. Had type 2 diabetes mellitus with HbA1c of ≥7.5 to ≤9.5% at Screening.
  3. Was treated with metformin alone (no treatment with any antidiabetic agents other than metformin within the 3 months prior to Screening) and was experiencing inadequate glycemic control. The participant should have received metformin monotherapy for ≥8 weeks prior to Screening at a stable dose ≥1500 mg). Participants with a maximum tolerated dose (MTD) that was documented to be less than 1500 mg of metformin could also be enrolled if this dose had been stable for 8 weeks prior to Screening.
  4. Was treated with antihypertensive therapy and had a mean, trough, sitting clinic systolic blood pressure (SBP) ≥135 and < 160 mm Hg on Day -1 (after washout of prior antihypertensive therapy) or the participant had not received antihypertensive treatment within 28 days before Screening and had a mean sitting clinic SBP ≥135 and < 160 mm Hg at the Screening Visit and on Day -1.
  5. Had clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or results that were deemed not clinically significant in this participant population for inclusion in this study, by the investigator.

Exclusion Criteria:

  1. Had a mean, trough, sitting clinic diastolic blood pressure (DBP) ≥ 100 mm Hg at Day -1.
  2. Had type 1 or poorly controlled type 2 diabetes mellitus (HbA1c >9.5%) at Screening.
  3. Was taking or expected to take an excluded medication.
  4. Had a history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
  5. Had clinically significant cardiac conduction defects (for example, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation).
  6. Had hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
  7. Had secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing's syndrome).
  8. Had renal dysfunction defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at Screening.
  9. Had albuminuria defined as >200 mg/g at Screening.
  10. Had known or suspected unilateral or bilateral renal artery stenosis.
  11. Had unexplained microhematuria ≥3 RBCs/HPF or macrohematuria at Screening and confirmed on repeat testing.
  12. Treatment with antidiabetic agents (sulfonylureas, glucagon-like peptide-1 (GLP-1) analogues, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides, thiazolidinediones (TZDs), and/or insulin) other than metformin during the 3 months prior to Screening.
  13. Had hyperkalemia as defined by central laboratory normal reference range 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: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Comparador de Placebo: Placebo QD
Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.
Medicamento: Placebo
Experimental: Azilsartan Medoxomil 40 mg QD
Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.
Medicamento: Azilsartan medoxomil
Outros nomes:
  • TAK-491
Experimental: Azilsartan Medoxomil 80 mg QD
Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Medicamento: Azilsartan medoxomil
Outros nomes:
  • TAK-491

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Descrição da medida
Prazo
Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure
Prazo: Baseline and Week 8
The change in trough systolic blood pressure measured at week 8 relative to baseline. The trough is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
Baseline and Week 8

Medidas de resultados secundários

Medida de resultado
Descrição da medida
Prazo
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Prazo: Baseline and Week 24
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 24 relative to baseline.
Baseline and Week 24
Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure
Prazo: Baseline and Week 8
The change in trough diastolic blood pressure measured at week 8 relative to baseline. The trough is the average of the non-missing values of the 3 serial trough sitting diastolic blood pressure measurements.
Baseline and Week 8
Change From Baseline in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in 24-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Baseline and Week 8
Change From Baseline in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in 24-hour mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Baseline and Week 8
Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in daytime (6am to 10pm) mean systolic blood pressure measured week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Baseline and Week 8
Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in daytime (6am to 10pm) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Baseline and Week 8
Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in nighttime (12am to 6am) mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Baseline and Week 8
Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in nighttime (12am to 6am) mean diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Baseline and Week 8
Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in 12-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded during the first 12 hours after dosing.
Baseline and Week 8
Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in 12-hour mean systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded during the first 12 hours after dosing.
Baseline and Week 8
Change From Baseline in the Trough (22 to 24 Hours After Dosing) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in trough systolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Baseline and Week 8
Change From Baseline in the Trough (22 to 24 Hours After Dosing) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring
Prazo: Baseline and Week 8
The change in trough diastolic blood pressure measured at week 8 relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Baseline and Week 8
Percentage of Participants Requiring Rescue Glycemic Therapy
Prazo: 24 Weeks
Percentage of participants requiring rescue glycemic therapy during study.
24 Weeks
Time to First Glycemic Rescue
Prazo: 24 Weeks
The time to the first instance of participants requiring glycemic rescue during study.
24 Weeks
Change From Baseline in HbA1c
Prazo: Baseline and Weeks 2, 4, 6, 8, 12, 16 and 20
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated relative to baseline.
Baseline and Weeks 2, 4, 6, 8, 12, 16 and 20
Change From Baseline in Fasting Plasma Glucose
Prazo: Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24
The change between the fasting plasma glucose value collected at each week indicated relative to baseline.
Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24
Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT)
Prazo: Baseline and Weeks 6 and 24
The change between the glucose value collected at weeks 6 and 24 relative to baseline. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Baseline and Weeks 6 and 24
Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT
Prazo: Baseline and Weeks 6 and 24
The change between the AUC for glucose at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Baseline and Weeks 6 and 24
Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT
Prazo: Baseline and Weeks 6 and 24
The change between the AUC for insulin at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Baseline and Weeks 6 and 24
Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT
Prazo: Baseline and Weeks 6 and 24
The change between the AUC for C-peptide at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Baseline and Weeks 6 and 24
Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT
Prazo: Baseline and Weeks 6 and 24
The change between the AUC for insulin/glucose ratio at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Baseline and Weeks 6 and 24
Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT
Prazo: Baseline and Weeks 6 and 24
The change between the AUC for glucagon at weeks 6 and 24 relative to baseline. AUC will be calculated based on measurements at 0, 30, 60 and 120 minutes. Oral glucose tolerance test measures glucose, insulin, C-peptide, insulin/glucose ratio, and glucagon through blood samples drawn at 0, 30, 60, and 120 minutes following consumption of a 75 g glucose beverage.
Baseline and Weeks 6 and 24

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Takeda

Investigadores

  • Diretor de estudo: Director, Clinical Science, Takeda

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 janeiro de 2012

Conclusão Primária (Real)

1 de maio de 2013

Conclusão do estudo (Real)

1 de maio de 2013

Datas de inscrição no estudo

Enviado pela primeira vez

18 de dezembro de 2011

Enviado pela primeira vez que atendeu aos critérios de CQ

20 de dezembro de 2011

Primeira postagem (Estimativa)

21 de dezembro de 2011

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

6 de maio de 2015

Última atualização enviada que atendeu aos critérios de controle de qualidade

20 de abril de 2015

Última verificação

1 de abril de 2015

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

  • TAK-491_304
  • U1111-1125-1197 (Identificador de registro: WHO)

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 .

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