Efficacy and Safety of Four Doses of Glycopyrronium Bromide (NVA237) in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD), in Comparison to an Active Comparator Tiotropium

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

This study will assess the efficacy and safety of glycopyrronium bromide (NVA237) in patients with stable COPD, in comparison to an active comparator.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: NVA237; Drug: Placebo; Drug: Tiotropium

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Vilvoorde, Belgium
    • Novartis Investigator Site
• France
  • Rueil-Malmaison,, France
    • Novartis Investigator Site
• Japan
  • Tokyo, Japan
    • Novartis Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 forced expiratory volume in 1 second (FEV1) ≥30% and < 80% of the predicted normal, and post-bronchodilator FEV1/forced vital capacity (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), narrow angle 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NVA237 12.5 µg; 12.5 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.	Drug: NVA237; single-dose dry-powder inhaler (SDDPI)
Experimental: NVA237 25 µg; 25 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.	Drug: NVA237; single-dose dry-powder inhaler (SDDPI)
Experimental: NVA237 50 µg; 50 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.	Drug: NVA237; single-dose dry-powder inhaler (SDDPI)
Experimental: NVA237 100 µg; 100 µg daily via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.	Drug: NVA237; single-dose dry-powder inhaler (SDDPI)
Placebo Comparator: Placebo; Placebo via single-dose dry-powder inhaler (SDDPI). At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.	Drug: Placebo; single-dose dry-powder inhaler (SDDPI)
Active Comparator: Tiotropium 18 µg; 18 µg od via Handihaler inhaler. Tiotropium was given open-label. At baseline visits for each of the 4 double-blind treatment periods, patients were randomized to one of 30 treatment sequences. There was a 7 day washout period between each sequence.	Drug: Tiotropium; Handihaler inhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 15min and 23h 45min post dosing.	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Means of FEV1 (L) at Day 1, by Timepoint	FEV1 was measured at 5, 15, 30 minutes, 1, 2, 3, 4, 5, 23 hours and 15 minutes, and 23 hours and 45 minutes post dose.	Day 1

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Verkindre C, Fukuchi Y, Flemale A, Takeda A, Overend T, Prasad N, Dolker M. Sustained 24-h efficacy of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients. Respir Med. 2010 Oct;104(10):1482-9. doi: 10.1016/j.rmed.2010.04.006. Epub 2010 Jun 11.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: July 13, 2007
• First Submitted That Met QC Criteria: July 13, 2007
• First Posted (Estimate): July 16, 2007

Study Record Updates

• Last Update Posted (Estimate): May 8, 2012
• Last Update Submitted That Met QC Criteria: May 3, 2012
• Last Verified: December 1, 2010

More Information

Terms related to this study

• Keywords: COPD, Age≥40 yrs, Glycopyrronium Bromide
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Glycopyrrolate; Tiotropium Bromide
• Other Study ID Numbers: CNVA237A2205