Once-Daily Glycopyrronium Bromide (NVA237) Provides Sustained 24-Hour Bronchodilation for COPD: Presented at ERS

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Title: Once-Daily Glycopyrronium Bromide (NVA237) Provides Sustained 24-Hour Bronchodilation for COPD: Presented at ERS
URL: http://www.pslgroup.com/dg/22E67E.htm
Doctor's Guide
October 8, 2008

By Chris Berrie

BERLIN -- October 8, 2008 -- Once-daily administration of the muscarinic antagonist glycopyrronium bromide (NVA237) at doses of 50 or 100 mcg shows rapid and sustained 24-hour bronchodilation and clinically relevant improvements in trough forced expiratory volume at first second (FEV₁) over placebo in patients with stable chronic obstructive pulmonary disease (COPD).

This 4-period, incomplete block crossover, double-blind, placebo-controlled study was presented here on October 7 at the European Respiratory Society (ERS) 18th Annual Congress by the study's designer Tim Overend, PhD, Clinical Research, Novartis Horsham Research Centre, Horsham, England, United Kingdom.

Bronchodilators are the cornerstone of treatment for COPD, a progressive disease that is characterised by airflow limitation that is only partially reversible.

Recent research demonstrated the bronchodilator efficacy of NVA237, Dr. Overend said, so he designed a study to evaluate the efficacy and safety of 4 doses of NVA237 administered via a single-dose, dry-powder inhaler in comparison with placebo and standard tiotropium in patients with stable COPD.

Inclusion criteria were moderate to severe stable COPD, age 40 years or older, 10-pack year or greater smoking history, postbronchodilator FEV₁ 30% to 80% predicted, and postbronchodilator FEV₁/forced vital capacity (FVC) <0.7.

The primary efficacy variable was trough FEV₁ at day 7, with those secondary of trough FEV₁ at day 1, and FEV₁ and FVC at individual time points post-dose on days 1 and 7.

Safety was monitored as adverse events, vital signs, electrocardiogram (ECG), haematology, blood chemistry, and urine analysis laboratory evaluations.

The researchers enrolled 83 patients a mean of 64.4 years old (male, 83.1%) and who were randomised to a sequence of 4 treatment periods of 7 days with the following: placebo; NVA237 12.5, 25, 50, or 100 mcg once daily; or open-label tiotropium 18 mcg once daily. There was a 7-day washout period between treatments.

Patients' baseline clinical characteristics included a mean COPD duration of 6.7 years, 48.2% were current smokers, predicted FEV₁ 46.0% prebronchodilator, 52.7% postbronchodilator, FEV₁/FVC postbronchodilator of 46.6%.

Mean trough FEV₁ at both days 1 and 7 were significantly increased in all active treatment groups over placebo (P < .05). While tiotropium promoted a significantly greater response at day 7 than the 2 lower NVA237 doses, at the 50- and 100-mcg doses of NVA237 the responses were numerically, but not significantly, greater than for tiotropium.

For the FEV₁ and FVC individual timepoints, all active treatments provided statistically significant improvements over placebo up to 24 hours after dosing on both days 1 and 7.

The 50- and 100-mcg doses of NVA237 produced statistically significant superior bronchodilation to tiotropium treatment up to 2 and 4 hours post-dosing, respectively (P < .05).

In the safety analysis, most adverse effects were mild and transient and were not dose related. There were no clinically relevant changes or abnormalities in any treatment group for vital signs, ECGs, or laboratory evaluations.

"We have demonstrated NVA237 to be an effective bronchodilator, in the context of the study, following 7 days of treatment, and we have shown a clear dose-response curve, with doses of 50 mcg and above showing statistically significant and clinically relevant bronchodilation," Dr. Overend said.

Thus, he added, "This product shows promise as a once-daily bronchodilator."

Funding for this study was provided by Novartis Pharma AG.

[Presentation title: Dose-Ranging Study to Assess the Efficacy and Tolerability of NVA237, a Once-Daily, Long-Acting Muscarinic Antagonist, in Patients With COPD. Abstract P3606]

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