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

• ClinicalTrials.gov Identifier: NCT00501852
• Recruitment Status: Completed
• First Posted: July 16, 2007
• Results First Posted: January 21, 2011
• Last Update Posted: May 8, 2012
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: NVA237; Drug: Placebo; Drug: Tiotropium	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 83 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: July 2007
• Actual Primary Completion Date: December 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Trough Forced Expiratory Volume in 1 Second (FEV1) Following 7 Days of Treatment [ Time Frame: Day 7 ]
   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.

Secondary Outcome Measures :

1. Least Squares Means of FEV1 (L) at Day 1, by Timepoint [ Time Frame: Day 1 ]
   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.

Eligibility Criteria

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

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 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

Contacts and Locations

Locations

Belgium

Novartis Investigator Site

Vilvoorde, Belgium

France

Novartis Investigator Site

Rueil-Malmaison,, France

Japan

Novartis Investigator site

Tokyo, Japan

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Chair: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Verkindre C, Fukuchi Y, Flémale 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.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00501852
• Other Study ID Numbers: CNVA237A2205
• First Posted: July 16, 2007
• Results First Posted: January 21, 2011
• Last Update Posted: May 8, 2012
• Last Verified: December 2010

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

COPD, Age≥40 yrs, Glycopyrronium Bromide

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Glycopyrrolate; Tiotropium Bromide; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Parasympatholytics; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Adjuvants, Anesthesia; Muscarinic Antagonists