Long Term Safety Study of NVA237 vs QAB149 in COPD Patients

Phase 3

Completed

Conditions: Chronic Obstructive Pulmonary Disease (COPD)

Interventions: Drug: Long-acting beta 2-agonist (LABA)
Drug: NVA237
Drug: Placebo

Registration Number: NCT01697696

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: The purpose of the study is to provide long term safety data of NVA237. This study will assess the safety and tolerability of a single dose strength of NVA237.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 511

Inclusion Criteria

Male or female patients with COPD according to GOLD 2011 who have signed informed consent.
Patients with airflow limitation of 30-80% post-bronchodilator FEV1 at run-in.
Current or ex-smokers with a smoking history of at least 10 pack years
Patients with a mMRC score of at least 2 at run-in.

Exclusion Criteria

Patients contraindicated for muscarinic antagonist agents and beta-2 agonists
Patients with a history of malignancy of any organ system, treated or untreated, within the last five years
Patients with narrow-angle glaucoma, BPH or bladder-neck obstruction or moderate-severe renal impairment or urinary retention
Patients who had a COPD exacerbation within 6 weeks prior to screening.
Patients requiring long term oxygen therapy prescribed for more than 12 hr per day.
Patients with a history of asthma.
Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to 40 years of age.
Patients with a blood eosinophil count of greater than 600 mm/3 during run-in
Patients with concomitant pulmonary disease
Patients with a history of certain cardiovascular co-morbid conditions
Patients with a diagnosis of alpha-1 anti-trypsin deficiency
Patients with active pulmonary tuberculosis
Patients in the active phase of a pulmonary rehabilitation programme
Other protocol-defined inclusion / exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Long-acting beta 2-agonist (LABA)	Long-acting beta 2-agonist (LABA)	QAB149
Long-acting beta 2-agonist (LABA)	Placebo	QAB149
NVA237 dose 1	NVA237	NVA237 dose 1

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate	52 weeks	Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.

Secondary Outcome Measures

Name	Time	Method
Time to Treatment Discontinuation	52 Weeks	Discontinuation rates are calculated using the Kaplan Meier method. The protocol allowed patients to discontinue outside the treatment window, hence we have a patient who discontinued at Day 388. Reasons for discontinuing treatment are Subject/guardian decision, Adverse event, Protocol deviation Lack of efficacy, Physician decision, Dosing error, Disease improvement under study, Pregnancy, Technical problems
Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints	-45 min and -15 minutes baseline and at Week 52	Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1.
Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints	-45 min and -15 minutes baseline and at Week 52	Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1.
Change From Baseline in COPD Symptoms	52 weeks	Percentage of days with 'no daytime symptoms' A day with 'no daytime symptoms' was defined from the diary data as any day where the patient had recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours (approximately 8 am to 8pm). However, a patient was not considered symptom free if they had used rescue medication that day even if his/her total daytime symptoms score was zero. Percentage of nights with 'no nighttime awakenings' A night with 'no nighttime awakenings' was defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the treatment period was divided by the total number of nights where diary recordings had been made in order to derive the percentage nights with 'no nighttime awakenings'.
Change From Baseline in Mean Daily Number of Puffs of Rescue Medication	52 weeks	The number of puffs of rescue medication taken in the previous 12 hours was recorded by the patients in the eDiary in the morning and evening. The total number of puffs of rescue medication per day over the 52 week treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator. Change from baseline in number of puffs were analyzed using a linear mixed model which contained treatment, baseline number of puffs, baseline smoking status, baseline ICS use and COPD disease severity as fixed effects with center as a random effect
Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52	-45 min and -15 minutes baseline and at Week 52	Change from baseline in pre-dose trough FEV1 was analyzed using a repeated measures analysis of covariance model which contained treatment, baseline FEV1, visit, baseline smoking status, baseline ICS use, COPD severity and treatment by visit, visit by baseline FEV1 interactions. An unstructured variance-covariance error matrix was used .Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose at Week 52. Baseline FEV1 was defined as the mean of the pre-dose FEV1 at -45 min and -15 min on Day 1.
Time to First COPD Exacerbation (Moderate or Severe).	52 weeks	COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. Rates are calculated using the Kaplan Meier method.