Phase III Results: Once-daily tiotropium Significantly Increases Time to First Severe Exacerbation and Reduces the Risk of Exacerbations in Asthma Patients Still Symptomatic Despite ICS/LABA Treatment
03 Sep, 2012, 09:51 BST
BRACKNELL, England, September 3, 2012 /PRNewswire/ --
- A significant proportion of asthma patients remain symptomatic despite current treatment options and may have asthma exacerbations[1]
- First phase III data for tiotropium delivered by the Respimat® Soft Mist™ Inhaler (SMI) in asthma demonstrated significant improvements in lung function in these adults[2]
- Tiotropium delivered by Respimat is not licensed for the treatment of asthma
- These data are also being published simultaneously online in the New England Journal of Medicine available at http://www.nejm.org.
Tiotropium delivered by the Respimat SMI significantly increased the time to first severe asthma exacerbation and in addition, reduced the risk of exacerbations (P = 0.03) in adults who remain symptomatic despite treatment with at least inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) in phase III PrimoTinA-asthma™ studies, presented today at the 2012 European Respiratory Society (ERS) congress. Tiotropium also significantly improved lung function in symptomatic asthma patients on ICS/LABA.[2]
The PrimoTinA-asthma studies (part of the ongoing phase III trial programme named UniTinA-asthma™) were two replicate double-blind parallel-group trials. Patients enrolled in the studies had a post-bronchodilator FEV1[*] <80% predicted and Asthma Control Questionnaire 7 (ACQ-7) score ≥1.5, while on at least high dose ICS/LABA. A total of 912 patients were randomised to additional once-daily tiotropium Respimat 5 mcg or placebo for 48 weeks.[2]
The pre-specified co-primary lung function endpoints included peak and trough FEV1 at 24 weeks. Adding tiotropium Respimat provided significant lung function improvements at 24 weeks, which were sustained over 48 weeks.[2]
For the third co-primary endpoint, in the pre-specified combined analysis of the two trials, the addition of tiotropium Respimat was associated with an increase in time to first severe asthma exacerbation (282 days vs. 226 days with placebo, as measured in the first quartile of patients.) This corresponds to a 21% relative risk reduction in numbers of patients with at least one severe exacerbation ([HR, 0.79; 95% CI 0.62 to 1.0; P=0.03] ARR 5.9% (26.9% vs. 32.8%))[2;3]
Further pre-specified secondary endpoints showed that the addition of tiotropium Respimat increased the time to first exacerbation of asthma (315 days, vs. 181 days with placebo) and a relative risk reduction of 31% of patients having any asthma exacerbation ([HR,0.69; 95% CI, 0.58 to 0.82; P<0.001] ARR 13.3% (49.9% vs. 63.2%))[2;3]
Dr Richard Russell, Consultant Chest Physician, Wexham Park Hospital and one of the UK study investigators said: "These results are promising for the many patients, who despite current treatment options, remain uncontrolled and prone to exacerbations."
Despite current treatment options, there still remains an unmet medical need in asthma, because a significant proportion of patients remain symptomatic and may experience asthma exacerbations.[1]
*. FEV1 Forced Expiratory Volume in one second
Dr Charles de Wet, Medical Director, Boehringer Ingelheim said: "We are excited by these results, which will likely be highly appreciated by both physicians and patients. The UniTinA-asthma trial programme is exploring whether tiotropium can address the clear unmet medical need seen in the significant number of asthma patients who remain symptomatic despite the available therapeutic options. This programme demonstrates our commitment to develop tiotropium Respimat for a wide range of asthma patients. These first results give us confidence that tiotropium Respimat has the potential to become an important new option in asthma treatment."
Notes to Editors
UniTinA-asthma™ Phase III trial programme ongoing
The PrimoTinA-asthma studies are part of Boehringer Ingelheim's comprehensive ongoing Phase III trial programme named UniTinA-asthma, which was designed to establish the efficacy and safety of tiotropium, delivered by the Respimat Soft Mist Inhaler (SMI) in patients with asthma. UniTinA-asthma includes trials in adults, adolescents and children and involves over 4,000 patients in more than 150 sites globally. Included in the UniTinA-asthma umbrella programme are the following studies:
- PrimoTinA-asthma™ Adult study - 205.416/.417 [4;5]
- MezzoTinA-asthma™ Adult study - 205.418/.419 [6;7]
- GraziaTinA-asthma™ Adult study - 205.442 [8]
- VivaTinA-asthma™ Paediatric study - 205.445/.446 [9;10]
- RubaTinA-asthma™ Adolescent study - 205.444 [11]
- PensieTinA-asthma™ Adolescent study - 205.456 [12]
About Asthma
Asthma is a chronic disorder of the airways, caused primarily by inflammatory processes and constriction of the smooth muscle in airway walls (bronchoconstriction). It is characterised by airflow obstruction and increased responsiveness of the airways to various stimuli (known as triggers). Symptoms include recurring episodes of wheezing, breathlessness, chest tightness and coughing. Typical asthma symptoms tend to be variable, intermittent and worse at night. Asthma is commonly triggered by viral respiratory infections, exercise, smoke, cold and allergens such as pollen, mould, animal fur and the house dust mite.[13]
The prevalence of asthma in England is among the highest in the world, with approximately 5.9% of the English population having asthma.[14]
Asthma is responsible for large numbers of hospital visits, the majority of which are unscheduled emergency admissions. 70% of unscheduled emergency admissions may have been preventable with appropriate early interventions.[14]
Epidemiological data have shown that many adults with asthma remain symptomatic despite current treatment options and have asthma exacerbations (attacks)[1] and might even require emergency care.[13]
There is no cure for asthma, although people may experience long periods of remission. Poorly controlled asthma can have a significant impact on the quality of life of the affected person and their family. Clinical measures such as lung function may not correlate with an individual's quality of life scores, but if asthma is well controlled, near maximal scores on quality of life instruments can be achieved.[13]
About Tiotropium
Tiotropium (Spiriva®) is a long-acting muscarinic antagonist (LAMA) with a mode of action that works by opening narrowed airways by targeting a dominant reversible mechanism - cholinergic bronchoconstriction and helping to keep them open for 24 hours with once-daily dosing.[15;16]
Tiotropium is licensed for the treatment of chronic obstructive pulmonary disorder (COPD) symptoms and has comprehensive clinical trial data, demonstrating an extensive wealth of experience since its introduction almost 10 years ago and over 25 million patient years of real life experience to support the efficacy and safety profile.[17]
About Respimat® Soft Mist™ Inhaler (SMI)
Respimat SMI is an innovative delivery device, which uses mechanical energy (a spring) to generate a long-lasting, slow-moving mist for inhalation.[16;18]
Boehringer Ingelheim: Leading respiratory forward
Treatment of respiratory diseases has been a major area of focus for Boehringer Ingelheim for over 90 years and significant resources are dedicated to research in this field.
In addition to novel treatments for asthma, Boehringer Ingelheim has also branched out into developing treatment options for other airway diseases, including COPD, lung cancer, idiopathic pulmonary fibrosis and other respiratory indications.
Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
A central element of Boehringer Ingelheim's culture is to be socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavours.
In 2011, Boehringer Ingelheim posted net sales of about 13.2 billion euro while spending almost 23.5% of net sales in its largest business segment Prescription Medicines on research and development.
For more information please visit http://www.boehringer-ingelheim.co.uk
References
(1) Rabe KF, Adachi M, Lai CK et al. Worldwide severity and control of asthma in children and adults: the global Asthma Insights and Reality surveys. J Allergy Clin Immunol 2004; 114(1):40-47.
(2) Kerstjens HAM, Engel M, Dahl R. Tiotropium in Asthma Poorly Controlled with Standard Combination Therapy. N Engl J Med (online) 2012.
(3) Kerstjens HAM, Engel M, Dahl R. Tiotropium in Asthma Poorly Controlled with Standard Combination Therapy - Supplementary Appendix. N Engl J Med (online) 2012.
(4) ClinicalTrials.gov. Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study I). Available at http://clinicaltrials.gov/ct2/show/NCT00772538 Accessed August 2012. 2012.
(5) ClinicalTrials.gov. Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study II). Available at http://clinicaltrials.gov/ct2/show/NCT00776984 Accessed August 2012. 2012.
(6) ClinicalTrials.gov. Evaluation of Tiotropium 2.5 and 5 Mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo and Salmeterol HydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 Mcg Twice Daily) in Patient With Moderate Persistent Asthma I. Available at http://clinicaltrials.gov/ct2/show/NCT01172808 Accessed August 2012. 2012.
(7) ClinicalTrials.gov. Evaluation of Tiotropium 2.5 and 5 Mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo and Salmeterol HydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 Mcg Twice Daily) in Patient With Moderate Persistent Asthma II. Available at http://clinicaltrials.gov/ct2/show/NCT01172821 Accessed August 2012. 2012.
(8) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Via Respimat in Adult Patients With Mild Persistent Asthma. Available at http://clinicaltrials.gov/ct2/show/NCT01316380 Accessed August 2012. 2012.
(9) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Moderate Persistent Asthma. Available at http://clinicaltrials.gov/ct2/show/NCT01634139 Accessed August 2012. 2012.
(10) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Respimat® Compared to Placebo in Children With Severe Persistent Asthma. Available at http://clinicaltrials.gov/ct2/show/NCT01634152 Accessed August 2012. 2012.
(11) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Moderate Persistent Asthma. Available at http://clinicaltrials.gov/ct2/show/NCT01257230 Accessed August 2012. 2012.
(12) ClinicalTrials.gov. Efficacy and Safety of 2 Doses of Tiotropium Respimat Compared to Placebo in Adolescents With Severe Persistent Asthma. Available at http://clinicaltrials.gov/ct2/show/NCT01277523 Accessed August 2012. 2012.
(13) National Institute for Health and Clinical Excellence (NICE). Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. 2008.
(14) Department of Health. An Outcomes Strategy for Chronic Obstructive Pulmonary Disease (COPD) and Asthma in England. 2011.
(15) Boehringer Ingelheim. Spiriva 18 microgram inhalation powder, hard capsule. Summary of Product Characteristics. (The Electronic Medicines Compendium) http://www.medicines.org.uk Accessed August 2012.
(16) Boehringer Ingelheim. Spiriva Respimat 2.5 micrograms solution for inhalation. Summary of Product Characteristics. (The Electronic Medicines Compendium) http://www.medicines.org.uk Accessed August 2012.
(17) Boehringer Ingelheim. Data on File: SPI11-03. 2011.
(18) Hochrainer D, Hölz H, Kreher C et al. Comparison of the aerosol velocity and spray duration of Respimat Soft Mist inhaler and pressurized metered dose inhalers. J Aerosol Med 2005; 18(3):273-282.
For further information, please contact:
Esta Keywood
Communications Executive
Boehringer Ingelheim Limited
Tel: +44(0)1344-742534
Bridget.Mullahy@boehringer-ingeheim.com
SOURCE Boehringer Ingelheim Limited