Safety and Tolerability of 28 Days Treatment With Glycopyrronium Bromide (NVA237) (100 or 200 µg Once a Day) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease

A Randomized, Double-blind, Placebo Controlled, Parallel Group, Multi-center Study, to Assess the Safety and Tolerability of 28 Days Treatment With NVA237 (100 or 200 µg Once a Day) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

This study assessed the safety/tolerability of 28 days of treatment with NVA237 100 µg and 200 µg once a day, compared to placebo in patients with moderate or severe Chronic Obstructive Pulmonary Disease (COPD).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: NVA237 100 µg; Drug: NVA237 200 µg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 281
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Rueil-Malmaison, France
    • Novartis Investigative Site
• Germany
  • Nurnberg, Germany
    • Novartis Investigative Site
• Netherlands
  • Arnhem, Netherlands
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain
    • Novartis Investigative Site
• Turkey
  • Istanbul, Turkey
    • Novartis Investigative Site
• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Novartis Investigative Site
    • Phoenix, Arizona, United States, 85006
      • Novartis Investigative Site
  • Colorado
    • Wheat Ridge, Colorado, United States, 80033
      • Novartis Investigative Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Novartis Investigative Site
  • Florida
    • Miami, Florida, United States, 33143
      • Novartis Investigative Site
    • Miami, Florida, United States, 33169
      • Novartis Investigative Site
    • Tamarac, Florida, United States, 33321
      • Novartis Investigative Site
  • Illinois
    • River Forest, Illinois, United States, 60305
      • Novartis Investigative Site
  • Kansas
    • Overland Park, Kansas, United States, 66210-2761
      • Novartis Investigative Site
  • Missouri
    • St. Chares, Missouri, United States, 63301
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97213
      • Novartis Investigative Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Novartis Investigative Site
    • Union, South Carolina, United States, 29379
      • Novartis Investigative Site
  • Texas
    • Ft Worth, Texas, United States, 76104
      • Novartis Investigative Site
    • Houston, Texas, United States, 77024
      • Novartis Investigative 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 or older
• Patients with moderate to severe COPD according to the GOLD Guidelines (2006)
• Patients who have smoking history of at least 10 pack years
• Patients with a post-bronchodilator Forced Expiratory Volume in One Second (FEV1) equal or greater than 30% of the predicted normal value and less than 80% of the predicted normal value, and post-bronchodilator FEV1/FVC less than 0.7 at visit 2
• Written informed consent by the patient prior to initiation of any study-related procedure

Exclusion Criteria:

• 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 during the screening period (up to visit 3).
• Patients who have had a respiratory tract infection within 6 weeks prior to visit 1 or during the screening period (up to visit 3).
• Patients with a history of asthma indicated by (but not limited to):

Blood eosinophil count > 400/mm3, onset of symptoms prior to age 40 years.

• Patients with a history of long QT syndrome or whose QTc measured at visit 1 is prolonged (more than 440 ms for males or more than 460 ms for females).
• Patients with a history of untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.
• Patients who, in the judgment of the investigator have a clinically relevant laboratory abnormality or a clinically significant condition such as (but not limited to) unstable ischemic heart disease, left ventricular failure, long term prednisone therapy, history of myocardial infarction, arrhythmia, narrow-angle glaucoma, symptomatic prostatic hyperplasia, bladder-neck obstruction or moderate to severe renal impairment that might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study.
• 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.

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo to NVA237 dry powder inhalation once a day for up to 28 days
Experimental: NVA237 100 µg	Drug: NVA237 100 µg; Dry powder inhalation once a day for up to 28 days; Other Names: Glycopyrronium Bromide
Experimental: NVA237 200 µg	Drug: NVA237 200 µg; Dry powder inhalation once a day for up to 28 days; Other Names: Glycopyrronium Bromide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Treatment With NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)	The assessment of safety was based on adverse events, particularly those adverse events known to be associated to treatment with muscarinic antagonists. A summary of adverse events is presented with this outcome, additional details are provided in Adverse Events Sections.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Squares Means of Trough Forced Expiratory Volume in One Second (FEV1), by Day	Forced expiratory volume maneuvers recorded using a calibrated spirometer. Trough forced expiratory volume in one second (FEV1) on Days 1 & 28 defined as the mean of the FEV1 values measured at 23 hours 15 minutes and 23 hours 45 minutes post-dose.	28 Days

Collaborators and Investigators

• Sponsor: Novartis

Publications and helpful links

General Publications

• Vogelmeier C, Verkindre C, Cheung D, Galdiz JB, Guclu SZ, Spangenthal S, Overend T, Henley M, Mizutani G, Zeldin RK. Safety and tolerability of NVA237, a once-daily long-acting muscarinic antagonist, in COPD patients. Pulm Pharmacol Ther. 2010 Oct;23(5):438-44. doi: 10.1016/j.pupt.2010.04.005. Epub 2010 Apr 21.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: August 1, 2007
• First Submitted That Met QC Criteria: August 1, 2007
• First Posted (Estimate): August 2, 2007

Study Record Updates

• Last Update Posted (Estimate): May 21, 2012
• Last Update Submitted That Met QC Criteria: May 14, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: COPD; glycopyrronium bromide; antimuscarinic
• 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; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Adjuvants, Anesthesia; Anticonvulsants; Glycopyrrolate; Bromides
• Other Study ID Numbers: CNVA237A2206