Seebri Breezhaler offers another treatment option in COPD

PHARMACOLOGY

Glycopyrronium is an inhaled long-acting anticholinergic for once daily administration.¹

CLINICAL STUDIES

The safety and efficacy of glycopyrronium were evaluated in two phase III studies, GLOW1 and GLOW2, involving adults 40 years or older with moderate to severe COPD. Participants had a smoking history of at least 10 pack-years, a post-bronchodilator forced expiratory volume in 1 second (FEV₁) of 30% or more but less than 80% of the predicted normal value, and a post-bronchodilator FEV₁/forced vital capacity (FVC) less than 0.70.^2,3

All participants completed a seven-day pre-screening period and a 14-day run-in period. Long-acting bronchodilator therapy was discontinued prior to the run-in period. Participants continued on inhaled or intranasal corticosteroids or H₁ antagonists if they were receiving a stable recommended dose before study entry.^2,3

The primary outcome measure was trough FEV₁ (mean of the values at 23hr 15min and 23hr 45min after dosing) at week 12.^2,3

Increased FEV₁

GLOW1 was a six-month study involving 822 patients who were randomised to receive glycopyrronium 50 microgram (corresponding to a delivered dose of 44 microgram) or placebo once daily via the Breezhaler device. Results showed that glycopyrronium had a rapid onset of action, with improvements in FEV₁ apparent within five minutes of dosing and sustained over 24 hours.² The least squares mean (LSM) trough FEV₁ at week 12 was significantly higher in the glycopyrronium group than in the placebo group, with a treatment difference of 108ml (p<0.001). Significant improvements in trough FEV₁ were maintained throughout the 26-week study period.²

Patients in the 12-month GLOW2 study (n=1,066) were randomised to receive glycopyrronium 50 microgram or placebo once daily via the Breezhaler device or open-label tiotropium 18 microgram (corresponding to a delivered dose of 10 microgram) once daily. The LSM trough FEV₁ at week 12 was significantly higher in the glycopyrronium and tiotropium groups than in the placebo group, with treatment differences of 97ml and 83ml, respectively (both p<0.001).³

Glycopyrronium produced significant improvements in peak FEV₁ compared with tiotropium in the first 4 hours after dosing on day 1 (p<0.001) and at week 26 (p<0.01), and comparable improvements at weeks 12 and 52.³

Breathlessness

In a pooled analysis of the two studies, significantly more patients receiving glycopyrronium experienced a reduction in breathlessness (≥1 point improvement on the Transition Dyspnoea Index) than with placebo (58.4% versus 46.4%, p<0.001). Similar results were observed for tiotropium (53.4%, p=0.009 compared with placebo).¹

Glycopyrronium also produced significant improvements in health-related quality of life. In the pooled analysis, significantly more patients receiving glycopyrronium achieved a ≥4 point improvement on the St George’s Respiratory Questionnaire compared with placebo at week 26 (57.8% versus 47.6%, p<0.001). In the tiotropium group, 61% achieved a ≥4 point improvement (p=0.004 compared with placebo).¹

Exacerbations

Compared with placebo, glycopyrronium significantly prolonged the time to first moderate or severe COPD exacerbation and significantly reduced the rate of moderate or severe exacerbations requiring oral corticosteroids or antibiotics during the first six months of treatment (0.53 versus 0.77 exacerbations per year, p<0.001).¹

Use of rescue medication (salbutamol) was also reduced in glycopyrronium-treated patients by 0.46 puffs per day (p=0.005) over 26 weeks and by 0.37 puffs per day (p=0.039) over 52 weeks compared with placebo, in GLOW1 and GLOW2, respectively.¹

Glycopyrronium was well tolerated in both studies with a similar incidence of adverse effects observed across the glycopyrronium, tiotropium and placebo groups.^2,3

Exercise tolerance

In a smaller three-week placebo crossover trial involving 108 patients with moderate to severe COPD (GLOW3), glycopyrronium 44 microgram daily was associated with immediate and significant improvement in exercise tolerance from day 1. Sustained reductions in lung hyperinflation and meaningful improvements in trough FEV1 and dyspnoea were also observed.⁴

References:

1. Seebri Breezhaler Summary of Product Characteristics, September 2012.
2. D’Urzo A et al. Respir Res 2011; 12: 156.
3. Kerwin E et al. Eur Respir J 2012; 40: 1106-14.
4. Beeh KM et al. Int J Chron Obstruct Pulmon Dis 2012; 7: 503-13.

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Further information: Novartis

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