12-week multi-center, randomized, double-blind, parallel-group study to assess the efficacy, safety and tolerability of the co-administration of NVA237 + indacaterol once daily vs. indacaterol once daily in patients with moderate to severe COPD.

Primary Study Objective

Demonstrate the superiority of NVA237 50 μg + indacaterol 150 μg administered once daily as compared with indacaterol 150 μg administered once daily in terms of trough FEV1 at Week 12.

The investigational treatment, NVA237 (glycopyrrolate) is an inhaled long acting muscarinic antagonist and the background treatment is Indacaterol an inhaled long acting β2 agonist currently on the market under the trade name Onbrez©.

Patients will be assigned in a randomized fashion to one of the following 2 treatment arms, in a ratio of 1:1:
• Indacaterol 150 μg o.d. plus placebo NVA237
or
• Indacaterol 150 μg o.d. plus NVA237 50 μg o.d.
 

Participation conditions

Inclusion Criteria

Patients eligible for inclusion in this study have to fulfill all of the following criteria:
• Male or female adults aged ≥40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure.
• Patients with moderate to severe stable COPD (Stage II or Stage III) according to the GOLD Guidelines 2010.
• Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7 at Visit 2 (Day -14).
• Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.).
• Symptomatic patients, according to daily electronic diary data between Visit 2 (-14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to randomization (Visit 3).

Exclusion Criteria

• Pregnant women or nursing mothers (pregnancy confirmed by positive hCG laboratory test).
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during the period of dosing of study treatment.
• Patients with Type I or uncontrolled Type II diabetes.
• Patients with a history of long QT syndrome or whose QTc measured at Visit 2 (Day -14) is prolonged (>450 ms for males and females) as confirmed by the central ECG assessor.
• Patients with paroxysmal (e.g. intermittent) atrial fibrillation are excluded. Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., beta blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, atrial fibrillation must be present at baseline and screening visits (confirmed by central reading), with a resting ventricular rate < 100/min.
• Patients who have a clinically significant ECG or laboratory abnormality at screening (Visit 2) or who for any other reason would be at potential risk if enrolled into the study, according to the judgment of the investigator.
• Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment.
• Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof.
• anticholinergic agents.
• long and short acting beta-2 agonists.
• sympathomimetic amines.
• lactose or any of the other excipients.
• Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
• Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH) or bladder-neck obstruction or moderate to severe renal impairment or urinary retention (BPH patients who are stable on treatment can be considered).
• Patients who have had a COPD exacerbation or respiratory tract infection which required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to screening (Visit 2)
or
Patients who develop such a COPD exacerbation or infection between screening (Visit 2) and treatment (Visit 3).
• Patients requiring long-term maintenance oxygen therapy prescribed for other than nocturnal use.
• Patients with any history of asthma or onset of respiratory symptoms prior to age 40 years.
• Patients with a blood eosinophil count > 600/mm3 during screening (Visit 2).
• Patients with allergic rhinitis who use a H1 antagonist or intra-nasal corticosteroids intermittently (N.B.: treatment with a stable dose or regimen is permitted).
• Patients with concomitant pulmonary disease (e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension unless secondary to COPD, active pulmonary tuberculosis). Patients with pulmonary lobectomy, lung volume reduction surgery, lung transplantation or α-1 anti-trypsin deficiency who otherwise meet all entrance criteria will be permitted to enroll in the study.
• Patients participating in or planning to participate in the active (evolving or changing) phase of a supervised pulmonary rehabilitation program during the study. (Maintenance programs that remain unchanged are permitted if the patient has been enrolled for 3 months or more).
• Patients receiving any protocol specified prohibited medications.
• Patients receiving medications in the classes listed in the protocol and who have not been stabilized for the specified period and their (respective) stated conditions met.
• Use of other investigational drugs (approved or unapproved) at the time of enrollment, or within 30 days or 5 half-lives of Visit 1, whichever is longer.
• Patients unable to use an electronic patient diary.
• Patients unable to use a single dose dry powder inhaler (SDDPI) device or a pressurized MDI (rescue medication) device or comply with the study regimen. Spacer devices are not permitted.
• Patients who have had live attenuated vaccinations within 30 days prior to the screening visit or during the run-in period. Inactivated influenza vaccination, pneumococcal vaccination or any other inactivated vaccine is acceptable provided it is not administered within 48 h prior to screening and randomization visits. Patients may return for rescreening after the appropriate period of time has elapsed.
• Patients who are, in the opinion of the investigator known to be unreliable or non-compliant.

Centre Hospitalier de Luxembourg (CHL), Department of Pneumology