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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04083339




Registration number
NCT04083339
Ethics application status
Date submitted
23/08/2019
Date registered
10/09/2019
Date last updated
8/12/2022

Titles & IDs
Public title
Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy
Scientific 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
Secondary ID [1] 0 0
AT-001-2001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetic Cardiomyopathies 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AT-001
Treatment: Drugs - Placebo

Experimental: AT-001 High dose - 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).

Experimental: AT-001 Low Dose - 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 Comparator - Placebo capsules will be used as comparator


Treatment: Drugs: AT-001
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

Treatment: Drugs: Placebo
Matching placebo will be administered as 3 capsules twice daily, before breakfast and before dinner
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Peak VO2 during cardio-pulmonary exercise test (CPET);
Timepoint [1] 0 0
15 months after randomization]
Secondary outcome [1] 0 0
Progression to overt heart failure (Stage C Heart Failure)
Timepoint [1] 0 0
27 months after randomization
Secondary outcome [2] 0 0
Changes in NT-proBNP
Timepoint [2] 0 0
27 months after randomization
Secondary outcome [3] 0 0
Changes in the modified Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Timepoint [3] 0 0
27 months after randomization

Eligibility
Key inclusion criteria
- Type 2 Diabetes Mellitus

- Diabetic cardiomyopathy

- Peak VO2 < 75% of predicted normal value based on age and gender
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
675
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,TAS,VIC
Recruitment hospital [1] 0 0
Prince Charles Hospital - Chermside
Recruitment hospital [2] 0 0
CORE Research Group Pty. Ltd. - Milton
Recruitment hospital [3] 0 0
AusTrials - Taringa
Recruitment hospital [4] 0 0
University of Tasmania at Hobart - Hobart
Recruitment hospital [5] 0 0
Barwon Health-University Hospital Geelong - Geelong
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
Baker Heart and Diabetes Institute - Melbourne
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
4064 - Milton
Recruitment postcode(s) [3] 0 0
4068 - Taringa
Recruitment postcode(s) [4] 0 0
7001 - Hobart
Recruitment postcode(s) [5] 0 0
3220 - Geelong
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Florida
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United States of America
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Illinois
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United States of America
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Massachusetts
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United States of America
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Mississippi
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United States of America
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Missouri
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United States of America
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New York
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Jaromer
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Czechia
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Pardubice
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Czechia
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Praha
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France
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Bondy
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France
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Créteil
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France
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Nantes
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France
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Valenciennes
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Germany
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Brandenburg
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Germany
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North Rhine Westphalia
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Germany
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Saxony
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Germany
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Berlin
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Germany
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Elsterwerda
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Hong Kong
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Sha Tin
Country [30] 0 0
Poland
State/province [30] 0 0
Borowska
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Poland
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Bialystok
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Poland
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Kraków
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Poland
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Poznan
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Poland
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Radom
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Poland
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Rzeszów
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Poland
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Wroclaw
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Poland
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Lódz
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Spain
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Barcelona
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Spain
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Murcia
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Spain
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A Coruña
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Spain
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Córdoba
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Spain
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Sevilla
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Spain
State/province [43] 0 0
Valencia
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United Kingdom
State/province [44] 0 0
Dundee
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United Kingdom
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Glasgow
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United Kingdom
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Leicester
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United Kingdom
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London
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United Kingdom
State/province [48] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Applied Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04083339
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James L Januzzi, MD
Address 0 0
Harvard Medical School (HMS and HSDM)
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04083339