Efficacy in COPD Maintenance

DUAKLIR Demonstrated Efficacy in 3 Trials

Significant improvement in lung function (peak) FEV1 vs mono-components and tiotropium at week 242,3

DUAKLIR vs mono-components and tiotropium (AMPLIFY trial)

Chart of improved lung function data in AMPLIFY trial

*The co-primary endpoint was change from baseline in 1-hour morning post-dose (peak) FEV1 at week 24 for DUAKLIR 253 mL vs aclidinium 169 mL (p<0.0001).

†The second co-primary endpoint was change from baseline in morning pre-dose (trough) FEV1 at week 24 for DUAKLIR 80 mL vs formoterol 25 mL (p<0.001).

‡Spiriva® is a registered trademark of Boehringer Ingelheim.

§Of 1,594 patients randomized, 1,583 were included in the ITT and safety populations, 1,403 in the per protocol population, and 1,356 (85.1%) remained on study treatment and completed the study.

At week 24, lung function improvement (peak) FEV1 was significantly greater with DUAKLIR vs either monotherapy2,6

DUAKLIR vs mono-components (AUGMENT trial)

Chart of improved lung function data in AUGMENT trial

*p<0.0001 vs DUAKLIR.

†The co-primary endpoint was change from baseline in 1-hour morning post-dose FEV1 at week 24 for DUAKLIR 253 mL vs aclidinium 169 mL (p<0.0001) and change from baseline to week 24 in morning pre-dose (trough) FEV1 DUAKLIR vs formoterol.

ITT=intention to treat; LS means=least square means.

Lung function improvement (peak) FEV1 was significantly greater with DUAKLIR vs either monotherapy or placebo at week 242,9

DUAKLIR vs mono-components (ACLIFORM trial)

Chart of improved lung function data in ACLIFORM trial

*p<0.0001 vs DUAKLIR.

†The co-primary endpoint was change from baseline in 1-hour morning post-dose FEV1 at week 24 for DUAKLIR 253 mL vs aclidinium 169 mL (p<0.0001).

ITT=intention to treat; LS means=least square means.

Sustained Improvement in Lung Function (peak) FEV1

In the AMPLIFY trial, the effect of DUAKLIR was sustained over the 24-week treatment period and FEV1* was statistically superior to either of its individual components and tiotropium at all timepoints2,3

Chart of sustained lung function data in AMPLIFY trial

*FEV1 obtained 1-hour post-morning dose.
†p<0.0001.
The second co-primary endpoint was change from baseline in morning pre-dose (trough) FEV1 at week 24 for DUAKLIR 80 mL vs formoterol 25 mL (p<0.001).
§Spiriva® is a registered trademark of Boehringer Ingelheim.

View Study Description
Clock icon with the number 5

Rapid Onset of Action–as Quickly as 5 Minutes3,6,9,10*†

DUAKLIR provides patients with better breathing in as fast as 5 minutes.

*DUAKLIR PRESSAIR displayed an increase in FEV1 compared to placebo of 108 mL (95% CI: 111, 145) within 5 minutes after the first dose, respectively. 

†DUAKLIR PRESSAIR is not indicated for the initial treatment of acute episodes of bronchospasm and does not replace the use of rescue inhalers.

The co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose (peak) FEV1 versus aclidinium 400 mcg and morning pre-dose (trough) FEV1 versus formoterol 12 mcg. 

24-Hour Control–Improving Breathing Both Day and Night

A serial spirometry sub-study of AMPLIFY, which evaluated the bronchodilation time-profile over 24 hours post-dose at week 242,3*†

Chart of 24-hour sub-study of improved lung function from AMPLIFY trial

Post-dose lung function over 24 hours at week 24.

*The co-primary endpoint was change from baseline in 1-hour morning post-dose (peak) FEV1 at week 24 for BID DUAKLIR 253 mL vs BID aclidinium 169 mL (p<0.0001).
†The second co-primary endpoint was change from baseline in morning pre-dose (trough) FEV1 at week 24 for BID DUAKLIR 80 mL vs BID formoterol 25 mL (p<0.001 ).
‡Spiriva® is a registered trademark of Boehringer Ingelheim.

View Study Description

Clear Reduction in Exacerbations

Aclidinium bromide, the LAMA component of DUAKLIR, significantly reduced the risk of COPD exacerbation and associated hospitalizations2,11,12

Downward arrow icon with 22 percent

Reduction in COPD Exacerbations*

Aclidinium compared to placebo
HR=0.78 (95% CI, 0.68-0.89)

Downward arrow icon with 35 percent

Reduction in Hospitalizations Due to COPD Exacerbations‡§

Aclidinium compared to placebo
HR=0.65 (95% CI, 0.48-0.89)

*Primary efficacy endpoint: Rate of moderate or severe COPD exacerbations during the 1st year of treatment.

†Patients with stable, moderate to very severe COPD, and a history of significant cardiovascular (CV) disease or cerebrovascular disease and/or significant risk factors. A moderate exacerbation is defined as increased COPD symptoms lasting ≥2 days requiring treatment with either antibiotics and/or systemic corticosteroids. A severe exacerbation is defined as an increase in COPD symptoms ≥2days that leads to hospitalization or death.

‡Secondary endpoint: On-study reductions in exacerbations of 17% and hospitalizations by 28%.

§Hospitalization due to COPD exacerbations was a secondary endpoint.

View Study Description

DUAKLIR PRESSAIR Safety Profile

Adverse reactions occurring in the DUAKLIR PRESSAIR group at a frequency of ≥3% and exceeding placebo*2

Treatment
Adverse Reactions
Preferred Term
DUAKLIR
PRESSAIR

(N=720)
Aclidinium
(N=722)
Formoterol
(N=716)
Placebo
(N=526)
Upper respiratory tract infection 8.9% 7.6% 8.9% 6.3%
Headache 6.3% 6.6% 7.7% 5.1%
Backpain 3.8% 3.3% 3.5% 3.4%

*Pooled safety analysis from two 24-week, placebo-controlled studies in adult patients with moderate-to-severe COPD.

†Includes viral upper respiratory tract infection and upper respiratory tract infection.

  • Other adverse reactions reported in clinical studies with an incidence of 1% to 3% with DUAKLIR PRESSAIR and more common than with placebo were cough, sinusitis, influenza, tooth abscess, insomnia, dizziness, dry mouth, oropharyngeal pain, muscle spasms, musculoskeletal pain, arthralgia, pain in extremity, urinary tract infection, and blood creatine phosphokinase increased
  • The adverse events reported in the 24-week active-controlled trial were consistent with those observed in 24-week placebo-controlled trials

Long-term Safety

DUAKLIR PRESSAIR 400/12 mcg twice BID was assessed in a 28-week safety extension trial in subjects who successfully completed trial 2 for a total treatment period of up to 52 weeks. The adverse reactions reported in the long-term safety trial were consistent with those observed in the 24-week, placebo-controlled trials. 

Indication and Usage

DUAKLIR PRESSAIR (aclidinium bromide/formoterol fumarate inhalation powder) is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

Important Safety Information

  • DUAKLIR PRESSAIR (aclidinium bromide/formoterol fumarate inhalation powder) is only indicated for use in COPD and is not indicated for use in asthma. Use of a long-acting beta2-adrenergic agonist (LABA) as monotherapy, including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, without an inhaled corticosteroid (ICS) is contraindicated in patients with asthma and increases the risk of asthma-related death. When LABA are used in fixed-dose combinations with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone.
  • DUAKLIR PRESSAIR is contraindicated in patients with severe hypersensitivity to milk proteins or who have hypersensitivity to aclidinium bromide or formoterol fumarate or any component of the product
  • DUAKLIR PRESSAIR is not indicated for the treatment of acute episodes of bronchospasm (i.e. rescue therapy)
  • Do not initiate DUAKLIR PRESSAIR with an additional medicine containing a LABA because of risk of overdose or in acutely deteriorating COPD
  • Immediate hypersensitivity reactions, including anaphylaxis, angioedema (swelling of lips, tongue, or throat), urticaria, rash, bronchospasm, or itching have occurred after administration of DUAKLIR PRESSAIR. Additionally, inhaled medicines, including DUAKLIR PRESSAIR, may cause paradoxical bronchospasm which may be life threatening. If any of these occurs, immediate treatment with a short acting bronchodilator should be initiated and treatment with DUAKLIR PRESSAIR should be stopped and alternative therapy initiated
  • DUAKLIR PRESSAIR should be used with caution in patients with cardiovascular and convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, hypokalemia, hyperglycemia, narrow-angle glaucoma or urinary retention. Instruct patients to consult a physician immediately should any signs or symptoms of acute narrow-angle glaucoma or prostatic hyperplasia or bladder-neck obstruction develop
  • The most common adverse reactions (≥3% incidence and more common than placebo) were upper respiratory tract infection (8.9% vs 6.3%), headache (6.3% vs 5.1%), and back pain (3.8% vs 3.4%) for DUAKLIR PRESSAIR vs placebo, respectively. Other adverse reactions reported in clinical studies (>1% but less than 3% and more common than placebo) with DUAKLIR PRESSAIR were cough, sinusitis, influenza, tooth abscess, insomnia, dizziness, dry mouth, oropharyngeal pain, muscle spasm, musculoskeletal pain, arthralgia, pain in extremity, urinary tract infection, and increased blood creatine phosphokinase

Medical Information

For answers to your medical questions about DUAKLIR PRESSAIR, please contact Circassia Medical Information at medinfo.us@circassia.com.

Please also see the full Prescribing Information, including Patient Information.

  • DUAKLIR PRESSAIR (aclidinium bromide/formoterol fumarate inhalation powder) is only indicated for use in COPD and is not indicated for use in asthma. Use of a long-acting beta2-adrenergic agonist (LABA) as monotherapy, including formoterol fumarate,
  • DUAKLIR PRESSAIR (aclidinium bromide/formoterol fumarate inhalation powder) is only indicated for use in COPD and is not indicated for use in asthma. Use of a long-acting beta2-adrenergic agonist (LABA) as

Indication and Usage

DUAKLIR PRESSAIR (aclidinium bromide/formoterol fumarate inhalation powder) is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

Important Safety Information

  • DUAKLIR PRESSAIR (aclidinium bromide/formoterol fumarate inhalation powder) is only indicated for use in COPD and is not indicated for use in asthma. Use of a long-acting beta2-adrenergic agonist (LABA) as monotherapy, including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, without an inhaled corticosteroid (ICS) is contraindicated in patients with asthma and increases the risk of asthma-related death. When LABA are used in fixed-dose combinations with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone.
  • DUAKLIR PRESSAIR is contraindicated in patients with severe hypersensitivity to milk proteins or who have hypersensitivity to aclidinium bromide or formoterol fumarate or any component of the product
  • DUAKLIR PRESSAIR is not indicated for the treatment of acute episodes of bronchospasm (i.e. rescue therapy)
  • Do not initiate DUAKLIR PRESSAIR with an additional medicine containing a LABA because of risk of overdose or in acutely deteriorating COPD
  • Immediate hypersensitivity reactions, including anaphylaxis, angioedema (swelling of lips, tongue, or throat), urticaria, rash, bronchospasm, or itching have occurred after administration of DUAKLIR PRESSAIR. Additionally, inhaled medicines, including DUAKLIR PRESSAIR, may cause paradoxical bronchospasm which may be life threatening. If any of these occurs, immediate treatment with a short acting bronchodilator should be initiated and treatment with DUAKLIR PRESSAIR should be stopped and alternative therapy initiated
  • DUAKLIR PRESSAIR should be used with caution in patients with cardiovascular and convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, hypokalemia, hyperglycemia, narrow-angle glaucoma or urinary retention. Instruct patients to consult a physician immediately should any signs or symptoms of acute narrow-angle glaucoma or prostatic hyperplasia or bladder-neck obstruction develop
  • The most common adverse reactions (≥3% incidence and more common than placebo) were upper respiratory tract infection (8.9% vs 6.3%), headache (6.3% vs 5.1%), and back pain (3.8% vs 3.4%) for DUAKLIR PRESSAIR vs placebo, respectively. Other adverse reactions reported in clinical studies (>1% but less than 3% and more common than placebo) with DUAKLIR PRESSAIR were cough, sinusitis, influenza, tooth abscess, insomnia, dizziness, dry mouth, oropharyngeal pain, muscle spasm, musculoskeletal pain, arthralgia, pain in extremity, urinary tract infection, and increased blood creatine phosphokinase

Medical Information

For answers to your medical questions about DUAKLIR PRESSAIR, please contact Circassia Medical Information at medinfo.us@circassia.com.

Please also see the full Prescribing Information, including Patient Information.

REFERENCES: 1. Loveridge B, et al. Am Rev Respir Dis. 1986;134(5):930-934. 2. Duaklir® Pressair® (aclidinium bromide/formoterol fumarate inhalation powder)[prescribing information]. Morrisville, NC: Circassia Pharmaceuticals Inc; 2019. 3. Sethi S, et al. International Journal of COPD. 2019;14:667-682. 4. Data on file, Circassia. 5. Jones PW, et al. Respir Med. 1991;85(suppl B):25-31. 6. D'Urzo AD, et al. Respir Res. 2014;15:123. 7. Miravitlles M, et al. Respir Res. 2014;15:122. 8. Balachandran J, et al. Am J Respir Grit Care Med. 2013;188:5-6. 9. Singh D, et al. BMC Pulmonary Medicine. 10. Cote CG, et al. Chest. 2008;134:104001. 11. Wise RA, et al. JAMA. 2019;321(17):1693-1701. 12. Tudorza® Pressair® (aclidinium bromide inhalation powder) [prescribing information]. Morrisville, NC: Circassia Pharmaceuticals Inc; 2019. 13. Ocakli B, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:2941-2947. 14. Centers for Disease Control and Prevention. Chronic Obstructive Pulmonary Disease Among Adults – United States, 2011. MMWR. Nov 2012;61(46);938-943. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6146a2.htm?s_cid=mm6146a2_w. Accessed April 7, 2016. 15. Centers for Disease Control and Prevention. Deaths: Leading Causes for 2017. National Vital Statistics Reports. 2019;68(6). https://www.cdc.gov/nchs/data/nvsr/nvsr68/nvsr68_06-508.pdf. Published June 24, 2019. Accessed August 19, 2019. 16. National Heart, Lung, and Blood Institute (NHLBI). Morbidity & Mortality: 2012 Chart Book on Cardiovascular, Lung, and Blood Diseases. http://www.nhlbi.nih.gov/files/docs/research/2012_ChartBook_508.pdf. Published February 2012. Accessed April 7, 2016. 17. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf. Updated November 2018. Accessed July 16, 2019. 18. Ford ES, Croft JB, Mannino DM, Wheaton AG, Zhang X, Giles WH. COPD Surveillance–United States, 1999-2011. Chest. 2013;144(1):284-305. 19. Chronic Obstructive Pulmonary Disease (COPD) Includes: Chronic Bronchitis and Emphysema. National Center for Health Statistics website. https://www.cdc.gov/nchs/fastats/copd.htm. Updated May 3, 2017. Accessed July 16, 2019. 20. American Lung Association. What Causes COPD. http://www.lung.org/lung-health-and-diseases/lung-disease-lookup/copd/symptoms-causes-risk-factors/what-causes-copd.html. Published 2016. Accessed April 7, 2016. 21. World Health Organization. Causes of COPD. http://www.who.int/respiratory/copd/causes/en/#. Accessed April 7, 2016.