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

NCT00501852 | Completed Phase 2 Results

• 1 other identifier: CNVA237A2205
• Study Type: interventional
• Target: 83
• Locations: 3 countries
• Sites: 3

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD, Age≥40 yrs, Glycopyrronium Bromide

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Least Squares Means of FEV1 (L) at Day 1, by Timepoint

  Day 1

Study Arms (6)

NVA237 12.5 µg

EXPERIMENTAL

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

NVA237 25 µg

EXPERIMENTAL

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

NVA237 50 µg

EXPERIMENTAL

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

NVA237 100 µg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Tiotropium 18 µg

ACTIVE COMPARATOR

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

Interventions

NVA237 DRUG

single-dose dry-powder inhaler (SDDPI)

NVA237 100 µg; NVA237 12.5 µg; NVA237 25 µg; NVA237 50 µg

Placebo DRUG

single-dose dry-powder inhaler (SDDPI)

Placebo

Tiotropium DRUG

Handihaler inhaler

Tiotropium 18 µg

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[Japan Respiratory Society 2001\].

You may not qualify if:

• 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):
• Blood eosinophil count \> 400/mm3
• Onset of symptoms prior to age 40 years.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigator Site

Vilvoorde, Belgium

Location

Novartis Investigator Site

Rueil-Malmaison, France

Location

Novartis Investigator site

Tokyo, Japan

Location

Related Publications (1)

• 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.

  PMID: 20541381 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Glycopyrrolate; Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2007
• First Posted: July 16, 2007
• Study Start: July 1, 2007
• Primary Completion: December 1, 2007
• Last Updated: May 8, 2012
• Results First Posted: January 21, 2011

Record last verified: 2010-12

Locations

JP (1); FR (1); BE (1)