DERIVE trial results presented as a late
breaker at ENDO 2018
AstraZeneca today announced the results of DERIVE, a Phase 3
study that evaluated the efficacy and safety of FARXIGA®
(dapagliflozin 10 mg), in patients with type 2 diabetes (T2D) with
moderate renal impairment (chronic kidney disease [CKD] stage 3A
with eGFR of 45-59 mL /min /1 .73m2). The results were presented at
the Endocrine Society’s 100th Annual Meeting and Expo (ENDO).
FARXIGA, an SGLT2 inhibitor, is indicated as an adjunct to diet
and exercise to improve glycemic control in adults with T2D
mellitus.1 FARXIGA is not indicated for weight loss or for the
treatment of CKD or hypertension.
The DERIVE trial randomized 321 patients with T2D (hemoglobin
A1C [HbA1C] between 7-11%; mean 8.2%) and stage 3A CKD (mean
estimated glomerular filtration rate [eGFR] 53 mL/min/1.73m2) from
eight countries and treated them with either dapagliflozin 10 mg or
placebo over 24 weeks.2 The study met its primary and secondary
efficacy endpoints including:
- Dapagliflozin 10 mg significantly
decreased mean HbA1C (-0.37%) vs placebo (-0.03%) from baseline to
week 24 (difference -0.34%, p < 0.001).
- Dapagliflozin 10 mg significantly
reduced mean body weight (-3.17 kg) vs placebo (-1.92 kg) from
baseline to week 24 (difference -1.25 kg, p < 0.001).
- Dapagliflozin 10 mg significantly
reduced mean fasting plasma glucose (-21.46 mg/dL) vs placebo
(-4.87 mg/dL) from baselines to week 24 (difference -16.6 mg/dL, p
= 0.001).
- Dapagliflozin 10 mg significantly
reduced mean systolic blood pressure (-4.8 mm Hg) vs placebo (-1.7
mm Hg) from baseline to week 24 (difference -3.1 mm Hg, p <
0.05).
The DERIVE trial also provides the following safety
information:
- Mean eGFR was decreased at 24 weeks
with dapagliflozin (-3.23 mL/min/1.73m2) vs placebo (-0.63
mL/min/1.73m2) (difference [95% CI]: -2.60 mL/min/1.73m2 [−5.03 vs
−0.16]).
- Overall, adverse events (AEs) occurred
in 41.9% of patients with dapagliflozin and 47.8% with placebo. AEs
related to study treatment by the investigators were reported in
10.6% of patients with dapagliflozin and 6.2% with placebo. The
most frequent AEs related to study treatment included urinary tract
infection and pollakiuria.
- No AEs of bone fracture or amputation
were reported in the study.
FARXIGA is contraindicated in patients with severe renal
impairment (eGFR <30 mL/min/1.73 m2), end-stage renal disease,
or in patients on dialysis. FARXIGA is not recommended in patients
with an eGFR persistently between 30 and <60 mL/min/1.73 m2. The
recommended starting dose for FARXIGA is 5 mg.
Jim McDermott, PhD, Vice President, US Medical Affairs, Diabetes
at AstraZeneca, said: “We are committed to helping patients with
complex and comorbid diseases like T2D and chronic kidney disease,
which is demonstrated through the breadth of our research and our
unique cardiovascular, renal and metabolic approach. The DERIVE
study will help us learn more and provide additional data for
FARXIGA in T2D.”
DERIVE adds important information to previous dapagliflozin
studies in patients with T2D diabetes and moderate renal
impairment. AstraZeneca is planning to submit the results of DERIVE
to the FDA to add to the breadth of data already contained within
the existing FARXIGA Prescribing Information.
According to the Centers for Disease Control and Prevention,
30.3 million people in the US have diabetes, and T2D accounts for
90% to 95% of all diabetes cases.3 T2D is the leading cause of CKD
in the US, affecting over 40% of patients, and sustaining control
of diabetes can help lower patients risk of developing severe
kidney disease.4, 5
Important Safety Information for FARXIGA®
(dapagliflozin)
Contraindications
- Prior serious hypersensitivity reaction
to FARXIGA
- Severe renal impairment (eGFR <30
mL/min/1.73 m2), end-stage renal disease, or patients on
dialysis
Warnings and Precautions
- Hypotension: FARXIGA causes
intravascular volume contraction, and symptomatic hypotension can
occur. Assess and correct volume status before initiating FARXIGA
in patients with impaired renal function, elderly patients, or
patients on loop diuretics. Monitor for hypotension
- Ketoacidosis has been reported
in patients with type 1 and type 2 diabetes receiving FARXIGA. Some
cases were fatal. Assess patients who present with signs and
symptoms of metabolic acidosis for ketoacidosis, regardless of
blood glucose level. If suspected, discontinue FARXIGA, evaluate
and treat promptly. Before initiating FARXIGA, consider risk
factors for ketoacidosis. Patients on FARXIGA may require
monitoring and temporary discontinuation in situations known to
predispose to ketoacidosis
- Acute Kidney Injury and Impairment
in Renal Function: FARXIGA causes intravascular volume
contraction and renal impairment, with reports of acute kidney
injury requiring hospitalization and dialysis. Consider temporarily
discontinuing in settings of reduced oral intake or fluid losses.
If acute kidney injury occurs, discontinue and promptly
treat.FARXIGA increases serum creatinine and decreases eGFR.
Elderly patients and patients with impaired renal function may be
more susceptible to these changes. Before initiating FARXIGA,
evaluate renal function and monitor periodically. FARXIGA is not
recommended in patients with an eGFR persistently between 30 and
<60 mL/min/1.73 m2
- Urosepsis and Pyelonephritis:
SGLT2 inhibitors increase the risk for urinary tract infections
[UTIs] and serious UTIs have been reported with FARXIGA. Evaluate
for signs and symptoms of UTIs and treat promptly
- Hypoglycemia: FARXIGA can
increase the risk of hypoglycemia when coadministered with insulin
and insulin secretagogues. Consider lowering the dose of these
agents when coadministered with FARXIGA
- Genital Mycotic Infections:
FARXIGA increases the risk of genital mycotic infections,
particularly in patients with prior genital mycotic infections.
Monitor and treat appropriately
- Increases in Low-Density Lipoprotein
Cholesterol (LDL-C) occur with FARXIGA. Monitor LDL-C and treat
per standard of care
- Bladder cancer: An imbalance in
bladder cancers was observed in clinical trials. There were too few
cases to determine whether the emergence of these events is related
to FARXIGA, and insufficient data to determine whether FARXIGA has
an effect on preexisting bladder tumors. FARXIGA should not be used
in patients with active bladder cancer. Use with caution in
patients with a history of bladder cancer
- Macrovascular Outcomes: There
have been no clinical studies establishing conclusive evidence of
macrovascular risk reduction with FARXIGA
Adverse Reactions
In a pool of 12 placebo-controlled studies, the most common
adverse reactions (≥5%) associated with FARXIGA 5 mg, 10 mg, and
placebo respectively were female genital mycotic infections (8.4%
vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and
urinary tract infections (5.7% vs 4.3% vs 3.7%).
Use in Specific Populations
- Pregnancy: Advise females of
potential risk to a fetus especially during the second and third
trimesters.
- Lactation: FARXIGA is not
recommended when breastfeeding.
Indication and Limitations of Use for FARXIGA®
(dapagliflozin)
FARXIGA is indicated as an adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes
mellitus.
FARXIGA is not recommended for patients with type 1 diabetes
mellitus or for the treatment of diabetic ketoacidosis.
Please see accompanying US Full Prescribing
Information and Medication Guide for
FARXIGA.
NOTES TO EDITORS
About AstraZeneca in Diabetes
AstraZeneca is pushing the boundaries of science with the goal
of developing life-changing medicines that aim to reduce the global
burden and complications of diabetes. As a main therapy area for
the company, we are focusing our research and development efforts
on diverse populations and patients with significant
co-morbidities, such as cardiovascular disease, obesity,
non-alcoholic steatohepatitis (NASH), and chronic kidney
disease.
Our commitment to diabetes is exemplified by the depth and
breadth of our global clinical research program. This commitment is
advancing the understanding of the treatment effects of our
diabetes medicines in broad patient populations, as well as
exploring combination products to help more patients achieve
treatment success earlier in their disease.
About AstraZeneca in Cardiovascular, Renal & Metabolic
Diseases
Cardiovascular, renal and metabolic diseases together form one
of AstraZeneca’s main therapy areas and platforms for future
growth. By following the science to understand more clearly the
underlying links between the heart, kidney and pancreas,
AstraZeneca is investing in the development of 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 CVMDs and even
regenerate organs and restore function, by continuing to deliver
transformative science that improves treatment practices and CVMD
health for millions of patients worldwide.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in
three main therapy areas - Oncology, Cardiovascular & Metabolic
Diseases and Respiratory. The Company also is selectively active in
the areas of Autoimmunity, Neuroscience and Infection. AstraZeneca
operates in over 100 countries and its innovative medicines are
used by millions of patients worldwide. For more information,
please visit www.astrazeneca-us.com and follow us on Twitter
@AstraZenecaUS.
1 AstraZeneca Pharmaceuticals. Prescribing Information: FARXIGA
(dapagliflozin). Accessed 12 March 2018
http://www.azpicentral.com/farxiga/pi_farxiga.pdf#page=12 Fioretto
P on behalf of the DERIVE Investigators and Study Team. Efficacy
and Safety of Dapagliflozin in Patients with Type 2 Diabetes and
Moderate Renal Impairment (Chronic Kidney Disease Stage 3A): The
DERIVE Study [presentation]. Presented at: Endocrine Society’s
100th Annual Meeting and Expo; March 19, 2018; Chicago, IL.3
National Diabetes Statistics Report, 2017 Estimates of Diabetes and
Its Burden in the United States. Centers for Disease Control and
Prevention. 2017. Available at:
https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf.
Accessed March 6, 2018.4 Bailey RA, Wang Y, Zhu V, Rupnow MF.
Chronic kidney disease in US adults with type 2 diabetes: an
updated national estimate of prevalence based on Kidney Disease:
Improving Global Outcomes (KDIGO) staging. BMC Research Notes.
2014;7:415. doi:10.1186/1756-0500-7-415.5 National Kidney
Foundation. Diabetes - A Major Risk Factor for Kidney Disease
Accessed March 2, 2018.
https://www.kidney.org/atoz/content/diabetes.
US-18844 Last updated
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