Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
- Conditions
- Diabetic Cardiomyopathies
- Interventions
- Drug: Placebo
- Registration Number
- NCT04083339
- Lead Sponsor
- Applied Therapeutics, Inc.
- Brief Summary
This is a multicenter, randomized, placebo-controlled, 2-part study to evaluate the safety and efficacy of AT-001 in adult patients (N=675) with Diabetic Cardiomyopathy at high risk of progression to overt heart failure.
- Detailed Description
The study consists of two consecutive parts: Part A and Part B. Part A will evaluate the safety and efficacy of two doses of AT-001 vs placebo. The primary objective of Part A is to demonstrate that AT-001 improves or prevents the decline of functional capacity in patients with Diabetic Cardiomyopathy. Part B is an extension of at least 12 months that will evaluate the safety and efficacy of chronic administration of AT-001 vs placebo in the same patients who had previously been evaluated in Part A. Assessments in Part B will include safety endpoints and exploratory clinical efficacy endpoints, i.e. death and hospitalization due to a cardiac event.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 675
- Type 2 Diabetes Mellitus
- Diabetic cardiomyopathy
- Peak VO2 < 75% of predicted normal value based on age and gender
- Prior diagnosis or signs/symptoms of overt/symptomatic heart failure / stage C heart failure
- Prior echocardiogrphic measurement of ejection fraction (EF) < 40%
- Prior acute coronary syndrome (ACS), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), coronary artery disease (CAD) or stroke
- Severe or moderate cardiac valve disease requiring intervention
- Clinically significant arrhythmia
- Prior diagnosis of congenital, infective, toxic, infiltrative, post-partum, or hypertrophic cardiomyopathy
- Blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at screening
- HbA1c >8.5% at screening
- Severe disease that would impact the performance of a cardio-pulmonary exercise test
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AT-001 Low Dose AT-001 The total daily doses will be of 2g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 2g/day of AT-001 is capable of producing a sufficient inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity). Placebo Comparator Placebo Placebo capsules will be used as comparator AT-001 High dose AT-001 The total daily doses will be of 3g. The dose selection and the frequency of dosing was based on the results of the phase 1/2 study demonstrating that 3g/day of AT-001 is capable of producing the maximum inhibition of the production of sorbitol (a pharmacodynamic biomarker of biological activity).
- Primary Outcome Measures
Name Time Method Peak VO2 during cardio-pulmonary exercise test (CPET); 15 months after randomization] Changes in Peak VO2 during cardio-pulmonary exercise test (CPET) from baseline to approximately Month 15 (15-18 months). A CPET may be repeated at approximately Month 27 (27-30 months).
- Secondary Outcome Measures
Name Time Method Progression to overt heart failure (Stage C Heart Failure) 27 months after randomization Defined by the occurrence of one of the following events: cardiovascular death, hospitalization for heart failure, urgent heart failure visit, new diagnosis of heart failure
Changes in NT-proBNP 27 months after randomization Changes in NT-proBNP may reflect worsening of cardiomyopathy over time
Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score 27 months after randomization Changes in the modified KCCQ may reflect deterioration of clinical status over time
Trial Locations
- Locations (79)
University of California, San Diego (UCSD)
πΊπΈLa Jolla, California, United States
University of California - Irvine Medical Center
πΊπΈOrange, California, United States
Clinical Trials Research
πΊπΈLincoln, California, United States
Progressive Medical Research
πΊπΈPort Orange, Florida, United States
ALL Medical Research, LLC
πΊπΈCooper City, Florida, United States
Mountain View Clinical Research - Greer
πΊπΈGreer, South Carolina, United States
AusTrials
π¦πΊTaringa, Queensland, Australia
FMC Science
πΊπΈLampasas, Texas, United States
Edumed s.r.o.
π¨πΏJaromΔΕ, Czechia
Prince Charles Hospital
π¦πΊChermside, Queensland, Australia
Ecogene-21
π¨π¦Chicoutimi, Quebec, Canada
Klinische Forschung Berlin GbR
π©πͺBerlin, Germany
Broward Research Center
πΊπΈPembroke Pines, Florida, United States
Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
πΊπΈTorrance, California, United States
Dallas Diabetes Research Center
πΊπΈDallas, Texas, United States
New Generation of Medical Research
πΊπΈHialeah, Florida, United States
Holston Medical Group
πΊπΈKingsport, Tennessee, United States
Universty of Mississippi Medical Center
πΊπΈJackson, Mississippi, United States
LMC Diabetes & Endocrinology Ltd. - Brampton
π¨π¦Brampton, Ontario, Canada
Southwest Family Medicine Associates
πΊπΈDallas, Texas, United States
Remington Davis, Inc.
πΊπΈColumbus, Ohio, United States
Brigham and Women's Hospital
πΊπΈBoston, Massachusetts, United States
Cleveland Clinic
πΊπΈCleveland, Ohio, United States
Juno Research, LLC - Northwest Site
πΊπΈHouston, Texas, United States
Juno Research, LLC - Southwest Houston Site
πΊπΈHouston, Texas, United States
Klinikum Frankfurt (Oder) GmbH
π©πͺFrankfurt (Oder), Brandenburg, Germany
Metabolic Institute of America
πΊπΈTarzana, California, United States
Westside Medical Associates of Los Angeles
πΊπΈBeverly Hills, California, United States
Praktyka Lekarska Ewa Krzyzagorska
π΅π±PoznaΕ, Poland
St. Louis Heart and Vascular Cardiology
πΊπΈSaint Louis, Missouri, United States
University of Texas Southwestern
πΊπΈDallas, Texas, United States
University of Tasmania at Hobart
π¦πΊHobart, Tasmania, Australia
Barwon Health-University Hospital Geelong
π¦πΊGeelong, Victoria, Australia
Austin Health
π¦πΊHeidelberg, Victoria, Australia
Baker Heart and Diabetes Institute
π¦πΊMelbourne, Victoria, Australia
C-Endo - Endocrinology Centre
π¨π¦Calgary, Alberta, Canada
LMC Diabetes & Endocrinology Ltd. - Toronto
π¨π¦Toronto, Ontario, Canada
Centre for Studies in Family Medicine, Western Centre for Public Health and Family Medicine, Western University
π¨π¦London, Ontario, Canada
Institut Universitaire de Cardiologie et de Pneumologie De Quebec
π¨π¦QuΓ©bec, Quebec, Canada
Nemocnice Pardubickeho kraje, a.s., Nemocnice Pardubice
π¨πΏPardubice, Czechia
Vseobecna fakultni nemocnice v Praze
π¨πΏPraha, Czechia
CHU Henri Mondor
π«π·CrΓ©teil, France
CHU de Nantes, Clinique d'Endocrinologie
π«π·Nantes, France
Herz-und Diabeteszentrum NRW Universitaetsklinik der Ruhr-Universitaet Bochum
π©πͺBad Oeynhausen, North Rhine Westphalia, Germany
Cardiologicum Pirna und Dresden
π©πͺDresden, Saxony, Germany
ZKS - Zentrum Klinische Studien Sudbrandenburg GmbH
π©πͺElsterwerda, Germany
Centrum Chorob Serca w USK
π΅π±WrocΕaw, Borowska, Poland
NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny
π΅π±BiaΕystok, Poland
Topolowa MEDICENTER MrΓ³zek & wspΓ³lnicy sp.j.
π΅π±KrakΓ³w, Poland
Centrum Twojego Zdrowia
π΅π±KrakΓ³w, Poland
Prywatny Gabinet Lekarski Centrum Medyczne Diabetika
π΅π±Radom, Poland
4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu
π΅π±WrocΕaw, Poland
ETG Lodz
π΅π±ΕΓ³dΕΊ, Poland
Hospital Clinico Universitario Virgen de la Arrixaca
πͺπΈEl Palmar, Murcia, Spain
Hospital Universitario Reina Sofia
πͺπΈCΓ³rdoba, Spain
Hospital de la Santa Creu i Sant Pau Barcelona
πͺπΈBarcelona, Spain
Hospital Germans Trias i Pujol
πͺπΈBadalona, Barcelona, Spain
Hospital Abente y Lago (Complejo Universitario de la CoruΓ±a)
πͺπΈA CoruΓ±a, Spain
Glenfield hospital
π¬π§Leicester, United Kingdom
Hospital Universitario Virgen Macarena
πͺπΈSevilla, Spain
Barts and The London School of Medicine & Dentistry
π¬π§London, United Kingdom
Hospital Clinico Universitario de Valencia
πͺπΈValencia, Spain
Wythenshawe Hospital
π¬π§Manchester, United Kingdom
Ninewells Hospital & Medical School
π¬π§Dundee, United Kingdom
LMC Diabetes & Endocrinology Ltd. - Etobicoke
π¨π¦Etobicoke, Ontario, Canada
UnityPoint Health - Methodist Hospital
πΊπΈPeoria, Illinois, United States
LMC Diabetes & Endocrinology Ltd. - Thornhill
π¨π¦Concord, Ontario, Canada
HΓ΄pital Jean-Verdier - AP-HP; Service Endocrinologie DiabΓ©tologie Nutrition
π«π·Bondy, France
Centre Hospitalier de Valenciennes
π«π·Valenciennes, France
CPS Research
π¬π§Glasgow, United Kingdom
Centrum Medyczne Medyk Stanislaw Mazur Sp. z o.o. SK
π΅π±RzeszΓ³w, Poland
South Oklahoma Heart Research
πΊπΈOklahoma City, Oklahoma, United States
Chear Center LLC
πΊπΈBronx, New York, United States
BC Diabetes
π¨π¦Vancouver, British Columbia, Canada
CORE Research Group Pty. Ltd.
π¦πΊMilton, Queensland, Australia
Mountain View Clinical Research
πΊπΈGreer, South Carolina, United States
Montefiore Medical Center
πΊπΈBronx, New York, United States
Erik Yee Mun George Fung
ππ°Sha Tin, Hong Kong
Prince of Wales Hospital; Chinese University of Hong Kong; Dept of Medicine and Therapeutics
ππ°Sha Tin, Hong Kong