Farxiga heart failure research broadened with new Phase III DETERMINE trials

First patients enrolled in two trials evaluating the effect of Farxiga on exercise capacity and heart failure symptoms

24 April 2019

The first patients have been enrolled in the Phase III DETERMINE trials evaluating the effect of Farxiga (dapagliflozin) on exercise capacity and heart failure (HF) symptoms.

The trials will assess these outcomes in patients who have HF with either a preserved or reduced ejection fraction – a measure of the percentage of blood leaving the heart with each contraction. They also will include patients with and without type-2 diabetes (T2D).

DETERMINE consists of two double-blind, randomised, placebo-controlled Phase III trials which will evaluate the effect of 16 weeks of treatment with Farxiga compared to placebo as measured by a 6-minute walk test, a standard assessment of exercise capacity in patients with HF. The key secondary outcome will be the measurement of a patient-reported outcome which assesses the impact of HF on patient well-being and ability to lead a normal and active life. One trial will enrol HF patients with preserved ejection fraction and the other will enrol HF patients who have reduced ejection fraction.

Both trials will explore the use of wearable devices to provide digital-reported patient outcomes data, merging technology and patient centric research to evolve the design of AstraZeneca clinical trials.

Elisabeth Björk, Senior Vice President, Head of late Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, said: “For many people with heart failure, there may be significant impairment in their exercise capacity and quality of daily life. The DETERMINE clinical trials reinforce our patient-centric approach to clinical research to evaluate the potential of Farxiga in addressing one of today’s most life-threatening and prevalent diseases, which effects 64 million people worldwide.”  

Scott D. Solomon, MD of Brigham and Women’s Hospital and Harvard Medical School, a lead investigator in the DETERMINE trials, said: “The concerns of people with heart failure and their families often extend beyond mortality and hospitalisations, to living a life as close to normal as possible with their disease symptoms. The DETERMINE trials will provide clinically relevant insights into how Farxiga may impact exercise capacity as well as the severity of symptoms experienced by people with heart failure regardless of their ejection fraction status.”

Professor John McMurray of University of Glasgow Institute of Cardiovascular & Medical Sciences, a lead investigator in the DETERMINE trials, said: “A decrease in physical activity and increase in the severity of symptoms correlates with a poor prognosis in people with heart failure. Therefore, treatment is aimed at reducing mortality and hospital admissions, and maintaining quality of life and independent living, without major symptom limitations. We will assess these important patient-centred outcomes in the DETERMINE trials using new wearable digital devices to collect information on patients’ every day activity.”

The DETERMINE trials are part of the extensive DapaCare clinical programme for Farxiga, which is generating data across a spectrum of patients with CV risk factors, established CV disease and varying stages of renal disease, both with and without T2D, many of whom are in need of new treatment options.

Farxiga is a selective inhibitor of human sodium-glucose co-transporter 2 (SGLT2 inhibitor) indicated as monotherapy and as part of combination therapy to improve glycaemic control in adult patients with T2D. Farxiga is not indicated to reduce the risk of CV events, heart failure or death.

About DETERMINE

DETERMINE-Preserved [NCT03877224] will investigate the effect of Farxiga compared to placebo on exercise capacity in patients with HF with preserved ejection fraction (LVEF>40%). Preserved ejection fraction occurs when the heart muscle contracts normally, but the ventricles do not relax as they should, resulting in a decreased total amount of blood pumped throughout the body. The trial will look to enrol 400 patients.

DETERMINE-Reduced [NCT03877237] will investigate the effect of Farxiga compared to placebo on exercise capacity in patients with HF with reduced ejection fraction (LVEF≤40%). Reduced ejection fraction occurs when the heart muscle does not contract effectively, and less oxygen-rich blood is pumped out to the body. The trial will look to enrol 300 patients.

About Farxiga

Farxiga (dapagliflozin) is a first-in-class, oral once-daily selective inhibitor of human sodium-glucose co-transporter 2 (SGLT2) indicated as both monotherapy and as part of combination therapy to improve glycaemic control, with the additional benefits of weight loss and blood pressure reduction, as an adjunct to diet and exercise in patients with T2D. Farxiga has a robust clinical trial programme exploring highly prevalent and interconnected diseases, including diabetes, heart failure and chronic kidney disease across more than 35 completed and ongoing Phase IIb/III trials in over 35,000 patients, as well as more than 1.8 million patient-years’ experience.

About AstraZeneca in heart failure

HF is a life-threatening disease that affects 64 million people worldwide.¹ One in five will develop the condition during the course of their life, and it is commonly linked to those living with T2D. HF impacts quality of life and overall health outcome.² Despite medical advances, it remains as prevalent and life-threatening as the four most common forms of cancer combined³. It is also the leading cause of hospitalisation for those over the age of 65 and represents a significant clinical and economic burden.⁴

AstraZeneca is committed to new ways to extend the therapeutic value of Farxiga in the treatment of people with heart failure including those with and without T2D. The company’s extensive clinical programme includes several global Phase III trials – DAPA-HF, DELIVER and DETERMINE – focusing on distinct and important areas of heart failure research in order to provide comprehensive clinical evidence around the disease. AstraZeneca is also investing its efforts in compelling new science through early-stage research of several potential medicines to address heart failure.

About AstraZeneca in Cardiovascular, Renal & Metabolism (CVRM)

Cardiovascular, renal and metabolism together form one of AstraZeneca’s main therapy areas and a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys and pancreas, AstraZeneca is investing in a portfolio of medicines to protect organs and improve outcomes by slowing disease progression, reducing risks and tackling co-morbidities. Our ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and cardiovascular health for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit astrazeneca.com and follow us on Twitter @AstraZeneca.

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References

^{1.     Vos T et al. Lancet. 2017;390:1211-1259}

^{2.     European Society of Cardiology (ESC). "One in five people will develop heart failure." ScienceDaily. 5 May 2015. Available at: www.sciencedaily.com/releases/2015/05/150505111934.htm.}

^{3.     Mamas MA. et al. Eur J of Heart Failure 2017.19:1095–1104}

^{4.     Azad, N., & Lemay, G. (2014). Management of chronic heart failure in the older population. Journal of geriatric cardiology: JGC, 11(4), 329-37.}