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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 actualizado 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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

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 estudio

Intervencionista

Inscripción (Actual)

105

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • 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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador de placebos: Placebo QD
Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.
Droga: Placebo
Experimental: Azilsartan Medoxomil 40 mg QD
Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.
Droga: Azilsartan medoxomil
Otros nombres:
  • TAK-491
Experimental: Azilsartan Medoxomil 80 mg QD
Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Droga: Azilsartan medoxomil
Otros nombres:
  • TAK-491

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure
Periodo de tiempo: 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 resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 24 Weeks
Percentage of participants requiring rescue glycemic therapy during study.
24 Weeks
Time to First Glycemic Rescue
Periodo de tiempo: 24 Weeks
The time to the first instance of participants requiring glycemic rescue during study.
24 Weeks
Change From Baseline in HbA1c
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Takeda

Investigadores

  • Director de estudio: Director, Clinical Science, Takeda

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de enero de 2012

Finalización primaria (Actual)

1 de mayo de 2013

Finalización del estudio (Actual)

1 de mayo de 2013

Fechas de registro del estudio

Enviado por primera vez

18 de diciembre de 2011

Primero enviado que cumplió con los criterios de control de calidad

20 de diciembre de 2011

Publicado por primera vez (Estimar)

21 de diciembre de 2011

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

6 de mayo de 2015

Última actualización enviada que cumplió con los criterios de control de calidad

20 de abril de 2015

Última verificación

1 de abril de 2015

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

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

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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