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

20. april 2015 oppdatert av: 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.

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Faktiske)

105

Fase

  • Fase 3

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

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

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

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.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Firemannsrom

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Placebo komparator: Placebo QD
Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.
Legemiddel: Placebo
Eksperimentell: Azilsartan Medoxomil 40 mg QD
Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.
Legemiddel: Azilsartan medoxomil
Andre navn:
  • TAK-491
Eksperimentell: Azilsartan Medoxomil 80 mg QD
Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
Legemiddel: Azilsartan medoxomil
Andre navn:
  • TAK-491

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 24 Weeks
Percentage of participants requiring rescue glycemic therapy during study.
24 Weeks
Time to First Glycemic Rescue
Tidsramme: 24 Weeks
The time to the first instance of participants requiring glycemic rescue during study.
24 Weeks
Change From Baseline in HbA1c
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Takeda

Etterforskere

  • Studieleder: Director, Clinical Science, Takeda

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. januar 2012

Primær fullføring (Faktiske)

1. mai 2013

Studiet fullført (Faktiske)

1. mai 2013

Datoer for studieregistrering

Først innsendt

18. desember 2011

Først innsendt som oppfylte QC-kriteriene

20. desember 2011

Først lagt ut (Anslag)

21. desember 2011

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

6. mai 2015

Siste oppdatering sendt inn som oppfylte QC-kriteriene

20. april 2015

Sist bekreftet

1. april 2015

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • TAK-491_304
  • U1111-1125-1197 (Registeridentifikator: WHO)

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

Abonnere