Date: 2013-05-21
Type of information:
phase: 3
Announcement: presentation of phase 3 data at the 2013 American Thoracic Society (ATS) congress in Philadelphia
Company: Boehringer Ingelheim (Germany)
Product: tiotropium* Respimat®
Action
mechanism: 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. Tiotropium is licensed for the treatment of chronic obstructive pulmonary disease (COPD) symptoms and has comprehensive clinical trial data, demonstrating extensive experience since its introduction almost 11 years ago and over 25 million patient years of real life experience to support the efficacy and safety profile.
Disease: asthma
Therapeutic area: Allergic diseases - Inflammatory diseases - Respiratory diseases
Country:
Trial
details: The PrimoTinA-asthma™ studies are a part of Boehringer Ingelheim’s large international phase III clinical programme named UniTinA-asthma™, which was designed to establish the efficacy and safety of tiotropium, delivered by the Respimat® Soft MistTM Inhaler (SMI) in patients with asthma.
UniTinA-asthmaTM includes a number of clinical studies investigating tiotropium Respimat® added to usual care in adults, adolescents and and children (age 1+) with persistent asthma across the spectrum of asthma severity. The current phase III programme consists of 11 studies and involves more than 4,000 patients in over 150 sites globally. Included in the UniTinA-asthma umbrella programme are the following studies:• PrimoTinA-asthma Adult study - 205.416/.417 5;6• MezzoTinA-asthma Adult study - 205.418/.419 7;8• GraziaTinA-asthma Adult study - 205.442 9• VivaTinA-asthma Paediatric study - 205.445/.446 10;11• RubaTinA-asthma Adolescent study - 205.444 12• PensieTinA-asthma Adolescent study - 205.456 13
Latest
news: * On May 21, 2013, results from pre-planned subgroup analyses of data from the PrimoTinA-asthma™ Phase III studies have been presented at the 2013 American Thoracic Society (ATS) congress in Philadelphia, Pennsylvania. Tiotropium delivered by the Respimat Soft Mist Inhaler increases time to first severe exacerbation (p=0.03) and first episode of asthma worsening (p<0.001) compared with placebo in symptomatic asthma patients receiving standard care treatments (ICS/LABA). These improvements were independent of age, allergic status, smoking status and bronchodilator response.The PrimoTinA-asthma studies were two replicate double-blind parallel-group trials including asthma patients aged 18-75 years, with a ?5-year history of asthma, diagnosed before the age of 40 years; and life-long non-smokers or ex-smokers (less than 10 pack-years 1 pack of cigarettes daily for 10 years) who quit smoking one or more years before study enrolment. A total of 912 patients were randomised to additional tiotropium Respimat 5 mcg (n=456) or placebo (n=456) for 48 weeks. In addition to ICS/LABA, patients in the PrimoTinA-asthma studies were permitted to receive additional background therapy, including theophylline, anti-allergic agents, stable systemic steroids and omalizumab.Asthma diagnosis in the PrimoTinA-asthma patient population was confirmed using criteria in line with current Global Initiative for Asthma guidelines. Patients with a diagnosis of COPD or other lung disease were excluded from the studies.Severe exacerbations were defined as asthma deterioration necessitating initiation or doubling of systemic glucocorticosteroids.* On February 23, 2013, Boehringer Ingelheim has presented new phase III data at the 2013 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting. Tiotropium delivered once daily via Respimat™ significantly improved lung function and reduced asthma exacerbations in patients who remain symptomatic despite treatment with at least ICS/LABA, irrespective of their allergic status.These were the main findings from a new subset of data from the Phase III UniTinA-asthma® programme presented for the first time at the 2013 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting in San Antonio, Texas.
The PrimoTinA-asthmaTM studies (1 and 2) were two replicate double-blind parallel-group trials including asthma patients with post-bronchodilator FEV1? <80% predicted and Asthma Control Questionnaire score ?1.5 while on at least ICS/LABA. A total of 912 patients were randomised to additional tiotropium Respimat®5 ?g (n=256) or placebo (n=256) for 48 weeks. In addition to ICS/LABA, patients in the trials were permitted to receive additional background therapy, including antihistamines, anti-allergic agents, nasal steroids and omalizumab. To investigate the relationship between response and the patients’ allergic status, a pre-planned sub-group analysis of the data from both PrimoTinA-asthmaTM studies (1 and 2) was carried out.
The subgroup of patients with potentially allergic asthma was identified using three criteria: total serum immunoglobulin E (IgE), blood eosinophils, or clinician judgment. Allergic status was positive if serum IgE was greater than 430 ?g/L, blood eosinophilia was greater than 0.6 × 109/L, or clinician judgement was “yes.”
In the overall study population, adding tiotropium Respimat®provided significant lung function improvements at 24 weeks, which were sustained over 48 weeks.Also, patients who received tiotropium Respimat® had a 21% risk reduction (HR 0.79, P=0.03) in time to first severe exacerbation. Severe exacerbations were defined as requiring systemic corticosteroids for at least 3 days.
Furthermore, the addition of tiotropium Respimat® reduced the risk of any asthma exacerbation, defined by a significant increase in symptoms or peak expiratory flow (PEF) drop ?30% over ?2 days, by 31% (P<0.0001).1
These significant improvements in lung function and reduction in exacerbations were also seen regardless of allergic status in each of the two trials. The pre-planned subgroup analyses showed that peak FEV1 improved with tiotropium in PrimoTinA-asthmaTM 1 irrespective of allergic status for IgE (P=0.86) and eosinophilia (P=0.46), and in PrimoTinA-asthmaTM 2 for IgE (P=0.98) and eosinophilia (P=0.18). There was also an improvement in clinician judgment in PrimoTinA-asthmaTM 2 (P=0.29).
Pre-dose (trough) FEV1 also improved with tiotropium compared with placebo, irrespective of allergic status, across all criteria in Trial 1 (IgE, P=0.85; eosinophilia, P=0.83; clinician judgment, P=0.15) and Trial 2 (IgE, P=0.58; eosinophilia, P=0.38; clinician judgment, P=0.85).
Pooled pre-specified data analyses from the two trials revealed that time to first severe asthma exacerbation and time to first asthma worsening were both increased with tiotropium compared with placebo not just in the overall analysis of the data, but also regardless of the patients’ allergic status, based on the three criteria.
Adverse events (AEs) were balanced between the allergic and non-allergic sub groups. The most frequently reported treatment-emergent AEs in both Phase III studies included asthma, peak expiratory flow (PEF) rate decreased and nasopharyngitis.
