Back to resultsSafety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
Primary Purpose
Diabetic Cardiomyopathies
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
AT-001
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Diabetic Cardiomyopathies focused on measuring Type 2 Diabetes, Aldose Reductase Inhibitor, Stage B Heart Failure, Stage C Heart Failure, Cardiopulmonary Exercise Test
Eligibility Criteria
Inclusion Criteria:
- Type 2 Diabetes Mellitus
- Diabetic cardiomyopathy
- Peak VO2 < 75% of predicted normal value based on age and gender
Exclusion Criteria:
- 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
Sites / Locations
- Westside Medical Associates of Los Angeles
- University of California, San Diego (UCSD)
- Clinical Trials Research
- University of California - Irvine Medical Center
- Metabolic Institute of America
- Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
- ALL Medical Research, LLC
- New Generation of Medical Research
- Broward Research Center
- Progressive Medical Research
- UnityPoint Health - Methodist Hospital
- Brigham and Women's Hospital
- Universty of Mississippi Medical Center
- St. Louis Heart and Vascular Cardiology
- Chear Center LLC
- Montefiore Medical Center
- Cleveland Clinic
- Remington Davis, Inc.
- South Oklahoma Heart Research
- Mountain View Clinical Research - Greer
- Mountain View Clinical Research
- Holston Medical Group
- Dallas Diabetes Research Center
- Southwest Family Medicine Associates
- University of Texas Southwestern
- Juno Research, LLC - Northwest Site
- Juno Research, LLC - Southwest Houston Site
- FMC Science
- Prince Charles Hospital
- CORE Research Group Pty. Ltd.
- AusTrials
- University of Tasmania at Hobart
- Barwon Health-University Hospital Geelong
- Austin Health
- Baker Heart and Diabetes Institute
- C-Endo - Endocrinology Centre
- BC Diabetes
- LMC Diabetes & Endocrinology Ltd. - Brampton
- LMC Diabetes & Endocrinology Ltd. - Thornhill
- LMC Diabetes & Endocrinology Ltd. - Etobicoke
- Centre for Studies in Family Medicine, Western Centre for Public Health and Family Medicine, Western University
- LMC Diabetes & Endocrinology Ltd. - Toronto
- Ecogene-21
- Institut Universitaire de Cardiologie et de Pneumologie De Quebec
- Edumed s.r.o.
- Nemocnice Pardubickeho kraje, a.s., Nemocnice Pardubice
- Vseobecna fakultni nemocnice v Praze
- Hôpital Jean-Verdier - AP-HP; Service Endocrinologie Diabétologie Nutrition
- CHU Henri Mondor
- CHU de Nantes, Clinique d'Endocrinologie
- Centre Hospitalier de Valenciennes
- Klinikum Frankfurt (Oder) GmbH
- Herz-und Diabeteszentrum NRW Universitaetsklinik der Ruhr-Universitaet Bochum
- Cardiologicum Pirna und Dresden
- Klinische Forschung Berlin GbR
- ZKS - Zentrum Klinische Studien Sudbrandenburg GmbH
- Erik Yee Mun George Fung
- Prince of Wales Hospital; Chinese University of Hong Kong; Dept of Medicine and Therapeutics
- Centrum Chorob Serca w USK
- NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny
- Topolowa MEDICENTER Mrózek & wspólnicy sp.j.
- Centrum Twojego Zdrowia
- Praktyka Lekarska Ewa Krzyzagorska
- Prywatny Gabinet Lekarski Centrum Medyczne Diabetika
- Centrum Medyczne Medyk Stanislaw Mazur Sp. z o.o. SK
- 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu
- ETG Lodz
- Hospital Germans Trias i Pujol
- Hospital Clinico Universitario Virgen de la Arrixaca
- Hospital Abente y Lago (Complejo Universitario de la Coruña)
- Hospital de la Santa Creu i Sant Pau Barcelona
- Hospital Universitario Reina Sofia
- Hospital Universitario Virgen Macarena
- Hospital Clinico Universitario de Valencia
- Ninewells Hospital & Medical School
- CPS Research
- Glenfield hospital
- Barts and The London School of Medicine & Dentistry
- Wythenshawe Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
AT-001 High dose
AT-001 Low Dose
Placebo Comparator
Arm Description
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).
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 capsules will be used as comparator
Outcomes
Primary Outcome Measures
Peak VO2 during cardio-pulmonary exercise test (CPET);
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
Progression to overt heart failure (Stage C Heart Failure)
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
Changes in NT-proBNP may reflect worsening of cardiomyopathy over time
Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Changes in the modified KCCQ may reflect deterioration of clinical status over time
Full Information
NCT ID
NCT04083339
First Posted
August 23, 2019
Last Updated
December 7, 2022
Sponsor
Applied Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04083339
Brief Title
Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
Official Title
Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF): A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 20, 2019 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Applied Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Cardiomyopathies
Keywords
Type 2 Diabetes, Aldose Reductase Inhibitor, Stage B Heart Failure, Stage C Heart Failure, Cardiopulmonary Exercise Test
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
675 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
AT-001 High dose
Arm Type
Experimental
Arm Description
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).
Arm Title
AT-001 Low Dose
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo Comparator
Arm Type
Placebo Comparator
Arm Description
Placebo capsules will be used as comparator
Intervention Type
Drug
Intervention Name(s)
AT-001
Intervention Description
AT-001 will be administered as 3 capsules twice daily, before breakfast and before dinner.
At present AT001 is the sole name for the active substance. No INN/genetic name is available to date
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo will be administered as 3 capsules twice daily, before breakfast and before dinner
Primary Outcome Measure Information:
Title
Peak VO2 during cardio-pulmonary exercise test (CPET);
Description
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).
Time Frame
15 months after randomization]
Secondary Outcome Measure Information:
Title
Progression to overt heart failure (Stage C Heart Failure)
Description
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
Time Frame
27 months after randomization
Title
Changes in NT-proBNP
Description
Changes in NT-proBNP may reflect worsening of cardiomyopathy over time
Time Frame
27 months after randomization
Title
Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Description
Changes in the modified KCCQ may reflect deterioration of clinical status over time
Time Frame
27 months after randomization
Other Pre-specified Outcome Measures:
Title
Worsening of diabetic cardiomyopathy
Description
Defined by either ≥ 20% increase in NT-proBNP or ≥ 5 point decrease in the mKCCQ score
Time Frame
15 and 27 months after randomization
Title
Changes in echocardiographic parameters
Description
Changes assessed on cardiac ultra-sound from baseline
Time Frame
27 months after randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Type 2 Diabetes Mellitus
Diabetic cardiomyopathy
Peak VO2 < 75% of predicted normal value based on age and gender
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James L Januzzi, MD
Organizational Affiliation
Harvard Medical School (HMS and HSDM)
Official's Role
Study Chair
Facility Information:
Facility Name
Westside Medical Associates of Los Angeles
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
University of California, San Diego (UCSD)
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Clinical Trials Research
City
Lincoln
State/Province
California
ZIP/Postal Code
95648
Country
United States
Facility Name
University of California - Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Metabolic Institute of America
City
Tarzana
State/Province
California
ZIP/Postal Code
91356
Country
United States
Facility Name
Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center
City
Torrance
State/Province
California
ZIP/Postal Code
90509
Country
United States
Facility Name
ALL Medical Research, LLC
City
Cooper City
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Facility Name
New Generation of Medical Research
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Facility Name
Broward Research Center
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Facility Name
Progressive Medical Research
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
UnityPoint Health - Methodist Hospital
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61602
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Universty of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
St. Louis Heart and Vascular Cardiology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63136
Country
United States
Facility Name
Chear Center LLC
City
Bronx
State/Province
New York
ZIP/Postal Code
10455
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Remington Davis, Inc.
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43215
Country
United States
Facility Name
South Oklahoma Heart Research
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73135
Country
United States
Facility Name
Mountain View Clinical Research - Greer
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29651
Country
United States
Facility Name
Mountain View Clinical Research
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29651
Country
United States
Facility Name
Holston Medical Group
City
Kingsport
State/Province
Tennessee
ZIP/Postal Code
37660
Country
United States
Facility Name
Dallas Diabetes Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
Southwest Family Medicine Associates
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
University of Texas Southwestern
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Juno Research, LLC - Northwest Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77040
Country
United States
Facility Name
Juno Research, LLC - Southwest Houston Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
FMC Science
City
Lampasas
State/Province
Texas
ZIP/Postal Code
76550
Country
United States
Facility Name
Prince Charles Hospital
City
Chermside
State/Province
Queensland
ZIP/Postal Code
4032
Country
Australia
Facility Name
CORE Research Group Pty. Ltd.
City
Milton
State/Province
Queensland
ZIP/Postal Code
4064
Country
Australia
Facility Name
AusTrials
City
Taringa
State/Province
Queensland
ZIP/Postal Code
4068
Country
Australia
Facility Name
University of Tasmania at Hobart
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7001
Country
Australia
Facility Name
Barwon Health-University Hospital Geelong
City
Geelong
State/Province
Victoria
ZIP/Postal Code
3220
Country
Australia
Facility Name
Austin Health
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Baker Heart and Diabetes Institute
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
C-Endo - Endocrinology Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2V 4J2
Country
Canada
Facility Name
BC Diabetes
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Y 3W2
Country
Canada
Facility Name
LMC Diabetes & Endocrinology Ltd. - Brampton
City
Brampton
State/Province
Ontario
ZIP/Postal Code
L6S 0C6
Country
Canada
Facility Name
LMC Diabetes & Endocrinology Ltd. - Thornhill
City
Concord
State/Province
Ontario
ZIP/Postal Code
L4K 4M2
Country
Canada
Facility Name
LMC Diabetes & Endocrinology Ltd. - Etobicoke
City
Etobicoke
State/Province
Ontario
ZIP/Postal Code
M9R 4E1
Country
Canada
Facility Name
Centre for Studies in Family Medicine, Western Centre for Public Health and Family Medicine, Western University
City
London
State/Province
Ontario
ZIP/Postal Code
N6G 2M1
Country
Canada
Facility Name
LMC Diabetes & Endocrinology Ltd. - Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4G 3E8
Country
Canada
Facility Name
Ecogene-21
City
Chicoutimi
State/Province
Quebec
ZIP/Postal Code
G7H 7K9
Country
Canada
Facility Name
Institut Universitaire de Cardiologie et de Pneumologie De Quebec
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
Edumed s.r.o.
City
Jaroměř
ZIP/Postal Code
55101
Country
Czechia
Facility Name
Nemocnice Pardubickeho kraje, a.s., Nemocnice Pardubice
City
Pardubice
ZIP/Postal Code
532 03
Country
Czechia
Facility Name
Vseobecna fakultni nemocnice v Praze
City
Praha
ZIP/Postal Code
128 08
Country
Czechia
Facility Name
Hôpital Jean-Verdier - AP-HP; Service Endocrinologie Diabétologie Nutrition
City
Bondy
ZIP/Postal Code
93140
Country
France
Facility Name
CHU Henri Mondor
City
Créteil
ZIP/Postal Code
94000
Country
France
Facility Name
CHU de Nantes, Clinique d'Endocrinologie
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Centre Hospitalier de Valenciennes
City
Valenciennes
ZIP/Postal Code
59322
Country
France
Facility Name
Klinikum Frankfurt (Oder) GmbH
City
Frankfurt (Oder)
State/Province
Brandenburg
ZIP/Postal Code
15236
Country
Germany
Facility Name
Herz-und Diabeteszentrum NRW Universitaetsklinik der Ruhr-Universitaet Bochum
City
Bad Oeynhausen
State/Province
North Rhine Westphalia
ZIP/Postal Code
32545
Country
Germany
Facility Name
Cardiologicum Pirna und Dresden
City
Dresden
State/Province
Saxony
ZIP/Postal Code
01277
Country
Germany
Facility Name
Klinische Forschung Berlin GbR
City
Berlin
ZIP/Postal Code
10787
Country
Germany
Facility Name
ZKS - Zentrum Klinische Studien Sudbrandenburg GmbH
City
Elsterwerda
ZIP/Postal Code
04910
Country
Germany
Facility Name
Erik Yee Mun George Fung
City
Sha Tin
Country
Hong Kong
Facility Name
Prince of Wales Hospital; Chinese University of Hong Kong; Dept of Medicine and Therapeutics
City
Sha Tin
Country
Hong Kong
Facility Name
Centrum Chorob Serca w USK
City
Wrocław
State/Province
Borowska
ZIP/Postal Code
50-556
Country
Poland
Facility Name
NZOZ Specjalistyczny Osrodek Internistyczno - Diabetologiczny
City
Białystok
ZIP/Postal Code
15-435
Country
Poland
Facility Name
Topolowa MEDICENTER Mrózek & wspólnicy sp.j.
City
Kraków
ZIP/Postal Code
31-506
Country
Poland
Facility Name
Centrum Twojego Zdrowia
City
Kraków
ZIP/Postal Code
31-526
Country
Poland
Facility Name
Praktyka Lekarska Ewa Krzyzagorska
City
Poznań
ZIP/Postal Code
61-655
Country
Poland
Facility Name
Prywatny Gabinet Lekarski Centrum Medyczne Diabetika
City
Radom
ZIP/Postal Code
26-600
Country
Poland
Facility Name
Centrum Medyczne Medyk Stanislaw Mazur Sp. z o.o. SK
City
Rzeszów
ZIP/Postal Code
35-005
Country
Poland
Facility Name
4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu
City
Wrocław
ZIP/Postal Code
50-981
Country
Poland
Facility Name
ETG Lodz
City
Łódź
ZIP/Postal Code
90-302
Country
Poland
Facility Name
Hospital Germans Trias i Pujol
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital Clinico Universitario Virgen de la Arrixaca
City
El Palmar
State/Province
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Hospital Abente y Lago (Complejo Universitario de la Coruña)
City
A Coruña
ZIP/Postal Code
15001
Country
Spain
Facility Name
Hospital de la Santa Creu i Sant Pau Barcelona
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Hospital Universitario Reina Sofia
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
ZIP/Postal Code
41009
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Ninewells Hospital & Medical School
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Facility Name
CPS Research
City
Glasgow
ZIP/Postal Code
G20 0XA
Country
United Kingdom
Facility Name
Glenfield hospital
City
Leicester
ZIP/Postal Code
LE3 9QP
Country
United Kingdom
Facility Name
Barts and The London School of Medicine & Dentistry
City
London
ZIP/Postal Code
EC1M 6BQ
Country
United Kingdom
Facility Name
Wythenshawe Hospital
City
Manchester
ZIP/Postal Code
M23 9Lt
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
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