Efficacy of LAMA Added to ICS in Treatment of Asthma (ELITRA)

Study Identifier:
CCD-05993AB1-02
ClinicalTrials.gov Identifier:
NCT02296411
EudraCT Identifier:
2014-001442-16
EU CT ID:
N/A
Study Contact Information:
N/A
Study Complete

Trial Documents

Clinical Study Report
Available Languages: English
Download document(s)

Study Details

Medical Condition
  • Asthma
Study Drug
  • Drug: CHF 5259 12.5 µg + Qvar
  • Drug: CHF 5259 placebo + Qvar
Date
Nov 2014 - Aug 2015
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Female & Male
Age: 18 - 75 Years
Requirements Information
Inclusion and Exclusion Criteria
Inclusion Criteria
  • Patient's written informed consent obtained prior to any study related procedures;
  • Male or female patients aged ≥18 and ≤75 years;
  • History of asthma ≥5 year and diagnosed before the age of 40 years;
  • Patients with uncontrolled asthma on low medium doses of ICS (200 - 1000 μg daily dose BDP non-extrafine or estimated clinical comparable dose) at a stable dose for at least 4 weeks prior to Screening visit;
  • Patients with a pre bronchodilator FEV1 ≥40% and \<90% of their predicted normal value, after appropriate washout from bronchodilators, at Screening visit and the end of the run in period;
  • Patients with a positive response to the reversibility test at Screening visit within 30 minutes after administration of 400 μg of salbutamol pMDI, defined as ΔFEV1 ≥12% and ≥200 mL over baseline; Note: In case this reversibility threshold was not met, the test could have been performed once before randomisation.
  • Patients with uncontrolled asthma evidenced by a score at the Asthma Control Questionnaire® (ACQ) ≥1.5 (criterion had to be met at Screening visit and the end of the run in period);
  • Patients with a co-operative attitude and ability to be trained to correctly use the pMDI and the electronic peak flow meter (e-peak flow meter). At the Screening visit (V1), all the above mentioned inclusion criteria were checked. At the Randomisation visit (V2), the following inclusion criteria were re checked: 5, 7 and 8.
Exclusion Criteria
  • Inability to carry out pulmonary lung function testing, to comply with study procedures or with study medication intake;
  • History of near fatal asthma or of a past hospitalisation for asthma in intensive care unit or of frequent exacerbations in the last year which, in the judgement of the Investigator, may have placed the patient at risk;
  • Hospitalisation, emergency room admission or use of systemic corticosteroids for asthma exacerbation in the 4 weeks prior to Screening visit or during the run-in period;
  • Lower respiratory tract infection in the 4 weeks before Screening visit or during the run-in period;
  • Patients who were in current therapy for gastroesophageal reflux disease (GERD) or patients with a medical history of GERD that led to asthma symptoms;
  • Patients with a seasonal worsening of asthma and who were not able to complete the study outside the relevant allergen season;
  • History of cystic fibrosis, bronchiectasis or alpha 1 antitrypsin deficiency, bronco carcinoma, lung carcinoma or any other significant lung disease which may have interfered with data evaluation;
  • Patients with a medical history or current diagnosis of COPD as defined by the Global Initiative for chronic obstructive lung disease (GOLD) guidelines (2014);
  • Current smokers or ex-smokers with total cumulative exposure equal or more than 10 pack years or having stopped smoking one year or less prior to Screening visit;
  • Any change in dose, schedule or formulation of ICS in the 4 weeks prior to Screening visit;
  • Patient had used any of the following treatments 4 weeks before Screening visit: inhaled LABAs, inhaled LAMAs, inhaled ICS/LABA fixed combinations, theophylline,leukotriene modifiers, cromolyn sodium, nedocromil sodium, systemic anticholinergics, systemic corticosteroids (12 weeks for slow release corticosteroids);
  • Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) unless are using at least one or more of the following reliable methods of contraception:
  • Placement of an intrauterine device or intrauterine system;
  • Hormonal contraception (implantable, injectable, patch, oral);
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical vaults/caps) with spermicidal foam/gel/film/cream/suppository;
  • Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); Reliable contraception was maintained throughout the study and for 1 week after the last study dose. Pregnancy tests were performed at study entry (a serum test at Screening visit and a urinary test at Screening and Randomisation visits) in all women of childbearing potential.
  • Any postmenopausal women (physiologic menopause defined as "12 consecutive months of amenorrhea") or women permanently sterilised (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy) were enrolled in the study.
  • Patients who received any investigational new drug or participated in clinical study either within the last 8 weeks (or 5 half-lives for biologic products with slow elimination) before Screening visit;
  • Patients who had clinically significant (CS) cardiovascular condition according to Investigator's judgement such as but not limited to: congestive heart failure (New York Heart Association \[NYHA\] class \>3), acute ischemic heart disease in the last year prior to study Screening, history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months (sustained means lasting more than 30 seconds or ending only with external action, or leads to hemodynamic collapse; non-sustained means \>5 beats \<30 seconds), impulse conduction blocks. Similarly, patients affected by permanent or paroxysmal atrial fibrillation were not considered for enrolment;
  • An abnormal and CS 12-lead electrocardiogram (ECG) that resulted in active medical problem which may have impacted the safety of the patient according to Investigator's judgement;
  • Patients whose electrocardiogram (12-lead ECG) showed Fridericia corrected QT (QTcF) \>450 ms for males or QTcF \>470 ms for females at Screening or at Randomisation visits;
  • Medical diagnosis of narrow angle glaucoma, clinically relevant prostatic hypertrophy or bladder neck obstruction that, in the opinion of the Investigator, prevented use of anticholinergic agents;
  • Unstable concurrent disease: e.g. uncontrolled hyperthyroidism, uncontrolled diabetes mellitus or other endocrine disease; significant hepatic impairment; with moderate to severe renal impairment (known creatinine clearance of ≤50 mL/min); uncontrolled gastrointestinal disease (e.g. active peptic ulcer); uncontrolled neurological disease; uncontrolled haematological disease; uncontrolled autoimmune disorders, or other laboratory abnormality that may have increased the risk associated with study participation or study medications administration and, in the judgment of theInvestigator, made the patient inappropriate for entry into this study, or placed the patients at undue risk or potentially compromised the results or interpretation of the study;
  • Patients having received a live attenuated virus vaccination within two weeks prior to Screening or during the run-in (inactivated influenza vaccination was acceptable provided it was not administered less than 48 hours prior to Screening);
  • Patients mentally or legally incapacitated;
  • Patients with a history of alcohol or drug abuse;
  • Patients with known intolerance/hypersensitivity or contra indication to treatment with β2 agonists, inhaled corticosteroids, anti cholinergics or propellant gases/excipients;
  • Patients with major surgery in the 3 months prior to Screening visit or planned surgery during the trial;
  • Patients treated with anti IgE antibodies;
  • Patients treated with non-potassium sparing diuretics (unless administered as a FDC with a potassium conserving drug), non-selective beta blocking drugs (except if taken at stable regimen for at least 2 months before Screening), quinidine, quinidine like anti arrhythmics, or any medication with a QTc prolongation potential or a history of QTc prolongation;
  • Patients treated with monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants;
  • Patients who are receiving any therapy that could have interfered with the study medications according to Investigator's opinion. At the Screening visit (V1), all the above mentioned exclusion criteria were checked. At the Randomisation visit (V2), the following exclusion criteria were re-checked: 1, 2, 3, 4, 5, 12, 15, 16, 18, 19, 23 and 27.
Healthy Volunteers
No

Protocol Summary

Primary objective

The primary objective was to evaluate the superiority of CHF 5259 (glycopyrronium bromide \[GB\]) in a pressurised metered dose inhaler (pMDI) (50 μg total daily dose) versus placebo in terms of forced expiratory volume in the first second (FEV1) area under the curve between time 0 and 12 hours (AUC0-12h) normalised by time on Day 42.

Key secondary objective

The key secondary objective was to evaluate the superiority of CHF 5259 pMDI (50 μg total daily dose) versus placebo in terms of peak FEV1 on Day 42.

Secondary objectives

The secondary objectives were:

  • To evaluate the effect of CHF 5259 pMDI on other lung function parameters and on clinical outcome measures;
  • To assess the safety and tolerability of study medications.

Study Locations

Location
Status
Location
Chiesi Clinical Trial Site 0107
Rousse, Bulgaria, 7002
Status
N/A
Location
Chiesi Clinical Trial Site 0106
Sevlievo, Bulgaria, 5400
Status
N/A
Location
Chiesi Clinical Trial Site 0101
Sofia, Bulgaria, 1000
Status
N/A
Location
Chiesi Clinical Trial Site 0109
Sofia, Bulgaria, 1336
Status
N/A
Location
Chiesi Clinical Trial Site 0108
Sofia, Bulgaria, 1407
Status
N/A
Location
Chiesi Clinical Trial Site 0102
Sofia, Bulgaria, 1431
Status
N/A
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