Efficacy and Safety of Four Doses of Glycopyrronium Bromide in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD), in Comparison to an Active Comparator Tiotropium

Condition(s) targeted: Chronic Obstructive Pulmonary Disease

Intervention: Glycopyrronium Bromide (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Novartis

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Chair, Affiliation: Novartis

This study will assess the efficacy and safety of glycopyrronium bromide in patients with stable COPD, in comparison to an active comparator.

Official title: A Randomized, Double-Blind, Placebo-Controlled, 4 Period Incomplete Block Cross-Over, Multi-Center, Multiple Dose (7 Days) Dose-Ranging Study to Assess the Efficacy and Safety of 4 Doses of NVA237 in Patients With Stable COPD, Compared to Seven Days Treatment With Tiotropium (18μg Once Daily, Open Label) as an Active Control

Study design: Treatment, Randomized, Double-Blind, Active Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome: The efficacy of NVA237 in patients with stable COPD - trough forced expiratory volume in 1 second (mean of 23h 15min and 23h 45min post dose) following 7 days of treatment, by comparing four doses of NVA237 (12.5, 25, 50 and 100 μg o.d.) with placebo

Secondary outcome: To explore additional efficacy, safety and tolerability of the four doses of NVA237 in comparison with placebo delivered by the Single Dose Dry Powder Inhaler (SDDPI) and with tiotropium (18μg) delivered by the Handihaler as an active control.

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion 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 COPD according to the Gold Guidelines (2006).

- Patients who have smoking history of at least 10 pack years. Ten pack-years is defined

as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years etc.

- Patients with a post-bronchodilator FEV1 ≥30% and < 80% of the predicted normal, and

post-bronchodilator FEV1/FVC < 0. 7 at Visit 2. For non-Japanese patients predicted FEV1 should be calculated according to Quanjer predictive equations [Quanjer PH 1993], for Japanese patients predicted FEV1 should be calculated according to Japanese Respiratory Society predictive tables [Japan Respiratory Society 2001].

Exclusion Criteria:

- Pregnant women or nursing mothers (pregnancy confirmed by positive urine pregnancy

test).

- Patients requiring oxygen therapy on a daily basis for chronic hypoxemia, or who have

been hospitalized for an exacerbation of their airways disease in the 6 weeks prior to Visit 1 or between Visit 1 and Visit 3.

- Patients who have had a respiratory tract infection within 6 weeks prior to Visit 1.

Patients who develop a respiratory tract infection during the screening period (up to Visit 3) must discontinue from the trial, but will be permitted to re-enroll at a later date (at least 6 weeks after the resolution of the respiratory tract infection).

- Patients who, in the judgment of the investigator or the responsible Novartis

personnel, have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, cancers, left ventricular failure, long term prednisone therapy, history of myocardial infarction, arrhythmia (all), narrowangle glaucoma, symptomatic prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment.

- Patients with a history of asthma indicated by (but not limited to):

1. Blood eosinophil count > 400/mm3

2. Onset of symptoms prior to age 40 years.

Other protocol-defined inclusion/exclusion criteria may apply

Novartis Investigator Site, Vilvoorde, Belgium

Novartis Investigator Site, Rueil-Malmaison,, France

Novartis Investigator site, Tokyo, Japan

Starting date: July 2007
Ending date: December 2007
Last updated: December 18, 2007