Study Analyzed SYMBICORT(R) in Children with Persistent Asthma

WILMINGTON, Del., May 20 /PRNewswire-FirstCall/ -- A new 12-week study(2)
examined safety and efficacy measures of the maintenance combination asthma
therapy, SYMBICORT(R) (budesonide/formoterol fumarate dehydrate) Inhalation
Aerosol(2) in treating mild to moderate persistent asthma in children ages 6
to 15 years old(2) who were previously treated with an inhaled corticosteroid
(ICS).(2) Of note, the study included efficacy assessments of nighttime
symptoms, nighttime rescue medication use and rescue medication-free days in
patients taking SYMBICORT compared to those taking formoterol dry powder
inhaler (DPI) or budesonide pressurized metered-dose inhaler (pMDI). Results
were presented today at the International Conference of the American Thoracic
Society held in Toronto, Canada, May 16-21, 2008.
"Children with asthma, who are not adequately controlled by ICS therapy,
may have their sleep affected by asthma symptoms,"(6) said Kathy Lampl, MD,
Director, Clinical Research, AstraZeneca. "Combination therapy with inhaled
ICS and LABA is one of the recommended regimens for children who have moderate
to severe persistent asthma or are not controlled with ICS therapy alone,
according to the NIH Guidelines."(7)
AstraZeneca (NYSE: AZN) anticipates filing a supplemental new drug
application with the Food and Drug Administration for the pediatric indication
of SYMBICORT in the first half of 2008.
About the Study (Abstracts #K66 and K67)
The safety profile and efficacy measures of SYMBICORT were assessed during
a 12-week randomized, double-blind, active-controlled study that evaluated 411
children ages 6 to 15 years old with mild to moderate persistent asthma(1,2)
previously treated with ICS therapy.(1,2) After a two-week period during which
patients discontinued their current asthma medications and received two
inhalations twice-daily of budesonide pMDI 40 micrograms (mcg), 128
patients(1,2) were randomized to receive treatment with SYMBICORT pMDI 40/4.5
mcg two inhalations twice-daily, 145(1,2) were randomized to receive
budesonide pMDI 40 mcg two inhalations twice-daily, and 138(1,2) were
randomized to receive formoterol DPI 4.5 mcg two inhalations twice-daily.(1,2)
The study assessed changes in predose AM and PM peak expiratory flow
(PEF),(1) which measures the maximum flow of air a person can blow out during
a forced breath (the maximum flow achieved during forced expiration),(3) and
predose forced expiratory volume in one second (FEV1),(1) which quantifies how
much air a person can exhale during a forced breath in the first second of
exhalation.(4) In addition, patients and caregivers were instructed to use an
electronic diary twice a day to record asthma symptom scores on a scale of 0
to 3 (0=none; 3=severe), nighttime symptoms due to asthma and nighttime rescue
medication use.(1) Safety assessments included reported adverse events,
electrocardiograms (ECG), clinical chemistry and vital signs.(2)
Results revealed significantly greater improvements from baseline to the
average over the treatment period in predose AM and PM PEF for SYMBICORT
(23.6 +/- 32.6 and 19.6 +/- 28.4) compared with its mono-components,
budesonide (8.0 +/- 26.7 and 6.4 +/- 25.0 L/min) and formoterol
(8.6 +/- 30.3 and 6.9 +/- 29.0 L/min).(1) SYMBICORT also demonstrated
significantly greater improvements (p<0.05) in predose and postdose FEV1
compared with budesonide.(1) Significant improvements in asthma control as
assessed by nighttime symptoms (p<0.05), nighttime rescue medication use
(p<0.05) and rescue medication-free days (p<0.05) were reported for patients
taking SYMBICORT compared to those taking formoterol.(1) Improvements in
nighttime asthma symptom scores and nighttime rescue medication use were
similar between patients taking SYMBICORT and those taking budesonide.(1)
Results also showed that SYMBICORT was well tolerated for 12 weeks with a
safety profile similar to its mono-components, budesonide and formoterol.(2)
The percentage of patients reporting any adverse events, regardless of
treatment, was similar for SYMBICORT (70.3%), budesonide (63.4%) and
formoterol (70.3%).(2) Most adverse events reported were of mild or moderate
intensity and did not lead to discontinuation.(2) Drug-related adverse events
for all treatment groups were SYMBICORT (3.1%); budesonide (3.4%); and
formoterol (6.5%).(2) No drug-related events led to the discontinuation of
SYMBICORT.(2) The most common drug-related adverse events reported were asthma
related adverse events, headache, insomnia and cough.(2)
About SYMBICORT
SYMBICORT is a combination therapy indicated for the long-term maintenance
treatment of asthma in patients 12 years of age and older.(5) Administered
twice daily, SYMBICORT is a combination of two proven asthma medications --
budesonide, an inhaled corticosteroid (ICS), and formoterol, a rapid and
long-acting beta2-agonist (LABA).(5) SYMBICORT does not replace fast-acting
inhalers and should not be used to treat acute symptoms of asthma.(5)
Important Safety Information
Long acting beta2-adrenergic agonists may increase the risk of
asthma-related death. Therefore, when treating patients with asthma, SYMBICORT
should only be used for patients not adequately controlled on other
asthma-controller medications (e.g., low-to-medium dose inhaled
corticosteroids) or whose disease severity clearly warrants initiation of
treatment with two maintenance therapies. Data from a large placebo-controlled
U.S. study compared the safety of another long-acting beta2-adrenergic agonist
(salmeterol) or placebo added to usual asthma therapy showed an increase in
asthma-related deaths in patients receiving salmeterol. This finding with
salmeterol may apply to formoterol (a long-acting beta2-adrenergic agonist),
one of the active ingredients in SYMBICORT.
SYMBICORT is not indicated for the relief of acute bronchospasm.
SYMBICORT should not be initiated in patients during rapidly deteriorating
or potentially life-threatening episodes of asthma.
Particular care is needed for patients who are transferred from
systemically active corticosteroids. Deaths due to adrenal insufficiency have
occurred in asthmatic patients during and after transfer from systemic
corticosteroids to less systemically available inhaled corticosteroids.
Patients who are receiving SYMBICORT twice daily should not use additional
formoterol or other long-acting inhaled beta2-agonists for any reason.
Common adverse events reported in clinical trials, occurring in greater
than or equal to 5 percent of patients, regardless of relationship to
treatment, including nasopharyngitis, headache, upper respiratory tract
infection, pharyngolaryngeal pain, sinusitis, and stomach discomfort.
For full Prescribing Information, please visit http://www.MySYMBICORT.com
About AstraZeneca
AstraZeneca is a major international healthcare business engaged in the
research, development, manufacturing and marketing of meaningful prescription
medicines and supplier for healthcare services. AstraZeneca is one of the
world's leading pharmaceutical companies with healthcare sales of $29.55
billion and is a leader in gastrointestinal, cardiovascular, neuroscience,
respiratory, oncology and infectious disease medicines. In the United States,
AstraZeneca is a $13.35 billion dollar healthcare business with 12,200
employees committed to improving people's lives. AstraZeneca is listed in the
Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index. For
more information visit http://www.astrazeneca-us.com.

References

1. Murphy, K.R., Pearlman, D.S., Uryniak, T., O'Brien, C.D., Mezzanotte,
W.S. Efficacy of Budesonide/Formoterol Pressurized Metered-Dose Inhaler
(BUD/FM pMDI) in Children With Asthma Previously Treated With Inhaled
Corticosteroids (ICSs) [poster]. American Thoracic Society, May 16-21,
2008, Toronto. Abstract #K66.

2. Pearlman, D.S., Murphy, K.R., Uryniak, T., O'Brien, C.D., Mezzanotte,
W.S. Safety of Budesonide/Formoterol Pressurized Metered-Dose Inhaler
(BUD/FM pMDI) in Children With Asthma Previously Treated With Inhaled
Corticosteroids (ICSs) [poster]. American Thoracic Society, May 16-221,
2008, Toronto. Abstract #K67.

3. Peak Flow Meters. Asthma and Allergy Foundation of America. Retrieved
on 25 April 2008. http://www.aafa.org/display.cfm?id=8&sub=16&cont=62

4. Know Your Asthma Numbers! Asthma and Allergy Foundation of America.
Retrieved on 25 April 2008.
http://www.aafa.org/display.cfm?id=8&sub=16&cont=586

5. Symbicort Prescribing Information.

6. Vargas PA, et al. Annals of Allergy Asthma and Immunology
2006;96(6):787-93.

7. National Asthma Education and Prevention Program. NIH/NHLBI.
Publication Number 08-4051, 2007. Available at
http://www.nhlbi.nih.gov/guidelines/asthma.

SOURCE AstraZeneca

Michele Meeker, +1-302-885-6351, michele.meeker@astrazeneca.com, or Katie
Neff, +1-302-885-9960, katie.neff@astrazeneca.com, both of AstraZeneca