Table 3.
Clinical evidence of the efficacy of glycopyrrolate monotherapy in patients with COPD
| Clinical trial | Treatment duration | Treatments | Key findings | ||||
|---|---|---|---|---|---|---|---|
| GLOW trials: double-blind, randomized, placebo-controlled studies in patients with moderate–severe COPD | |||||||
| Phase III GLOW141 | 26 weeks | Glycopyrrolate 50 µg QD (n=552), placebo (n=270) | Glycopyrrolate significantly increased trough FEV1 vs placebo at week 12 (LSM treatment difference 0.108 L, P<0.001), increase maintained at week 26 (LSM treatment difference 0.113 L, P<0.001) Significant improvements in dyspnea (TDI focal score 1.84 vs 0.80 points, P<0.001) and time to first moderate/severe exacerbation (P=0.023) vs placebo at week 26 |
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| Phase III GLOW242 | 52 weeks | Glycopyrrolate 50 µg QD (n=529), placebo (n=269), open-label tiotropium 18 µg QD (n=268) | Glycopyrrolate significantly increased trough FEV1 vs placebo at week 12 (LSM treatment difference 97 mL, P<0.001) Glycopyrrolate significantly increased trough FEV1 vs tiotropium at week 26 (LSM treatment difference 50 mL, P<0.01), while trough FEV1 was similar at weeks 12 and 52 (LSM treatment difference 14 and 19 mL, respectively) Significant improvements in dyspnea at week 26 (TDI focal score 2.13 vs 1.32, P=0.002) and risk of exacerbations at week 52 (P=0.001) vs placebo |
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| Phase III GLOW3 crossover43 | 3 weeks | Glycopyrrolate 50 µg QD, then placebo (n=55); placebo, then glycopyrrolate 50 µg QD (n=53) | Glycopyrrolate significantly improved submaximal exercise endurance time vs placebo on day 1 (P<0.001), and this improvement increased at day 21 (P<0.001) | ||||
| Phase III GLOW545 | 12 weeks | Glycopyrrolate 50 µg QD (n=327), tiotropium 18 µg QD (n=330) | Glycopyrrolate was noninferior to tiotropium for trough FEV1 at week 12 (LSM treatment difference 0 L, P<0.001) Glycopyrrolate had a significantly faster onset of action on day 1 than tiotropium (postdose FEV1 at 0- to 4-hour time points, all P<0.001) |
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| GLOW746 | 26 weeks | Glycopyrrolate 50 µg QD (n=306), placebo (n=154) | Glycopyrrolate significantly improved trough FEV1 vs placebo at week 12 (LSM treatment difference 141 mL, P<0.001) Glycopyrrolate significantly improved SGRQ scores (LSM treatment difference −4.92 points, P<0.001) and dyspnea severity (LSM treatment difference 1 point, P<0.001) at week 26 vs placebo |
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| SPRING trial: randomized, blinded study in patients with moderate–severe COPD | |||||||
| SPRING crossover47 | 4 weeks | Glycopyrrolate 50 µg QD, then tiotropium 18 µg QD; tiotropium 18 µg QD, then glycopyrrolate 50 µg QD (n=126) | On day 1, glycopyrrolate 50 µg treatment significantly improved FEV1 AUC0–4 after the first dose compared with tiotropium 18 µg (LSM treatment difference 0.030 L, P=0.025) Improvements in morning symptoms of COPD were similar between treatments |
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| GEM trials: Phase III, double-blind, randomized, placebo-controlled studies in patients with COPD and moderate–severe airflow limitation | |||||||
| GEM148 | 12 weeks | Glycopyrrolate 15.6 µg BID (n=222), placebo (n=219) | Glycopyrrolate significantly improved FEV1 AUC0–12 vs placebo at week 12 (LSM treatment difference 0.139 L, P<0.001) Glycopyrrolate significantly improved TDI (LSM treatment difference 0.92 points, P=0.003) and SGRQ scores (LSM treatment difference −2.8 points, P=0.016) vs placebo at week 12 |
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| GEM249 | 12 weeks | Glycopyrrolate 15.6 µg BID (n=216), placebo (n=216) | Glycopyrrolate significantly improved FEV1 AUC0–12 vs placebo at day 1 (LSM treatment difference 0.119 L, P<0.001), improvement maintained at week 12 (LSM treatment difference 0.123 L, P<0.001) Glycopyrrolate significantly improved SGRQ scores (LSM treatment difference −5.2 points, P<0.001) vs placebo at week 12 |
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| GOLDEN trials: Phase III, randomized studies of nebulized glycopyrrolate in patients with moderate–very severe COPD | |||||||
| Double-blind, placebo-controlled GOLDEN 3 and GOLDEN 438 | 12 weeks | Glycopyrrolate 25 µg BID (n=431), glycopyrrolate 50 µg BID (n=432), placebo (n=430) | At week 12, treatment with glycopyrrolate 25 and 50 µg BID resulted in significant and clinically important improvements in trough FEV1 vs placebo (GOLDEN 3 [LSM difference 0.105 and 0.126 L, respectively] and GOLDEN 4 [LSM difference 0.084 and 0.082 L, respectively], all P≤0.0001) At week 12, glycopyrrolate 25 and 50 µg BID significantly improved trough FVC vs placebo (GOLDEN 3 [LSM difference 0.149 and 0.167 L, respectively; both P<0.001], GOLDEN 4 [LSM difference 0.130 and 0.113 L, respectively; P<0.01]) At week 12/end of study, glycopyrrolate 25 and 50 µg BID significantly increased SGRQ scores vs placebo (GOLDEN 3 [LSM difference −3.072, P<0.05 and −1.848 points, P=NS, respectively]; GOLDEN 4 [LSM difference −3.585 and −3.557 points, respectively; P<0.01]) |
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| Open-label, active-controlled GOLDEN 551 | 48 weeks | Glycopyrrolate 50 µg BID (n=621), tiotropium 18 µg QD (n=466) | Glycopyrrolate treatment improved trough FEV1 from baseline, which was maintained until week 48 (LSM change from baseline at week 48 0.069 L) Change from baseline in FEV1 at 48 weeks did not differ significantly between glycopyrrolate and tiotropium |
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| Randomized, double-blind studies of glycopyrrolate delivered using co-suspension delivery technology in patients with moderate–severe COPDa | |||||||
| Chronic-dosing, Phase II, crossover trial52 | 2 weeks | Glycopyrrolate 18, 9, 4.6, 2.4, 1.2, 0.6 µg BID (n=64, 64, 62, 64, 57, 59, respectively), open-label tiotropium 18 µg QD (n=62), placebo BID (n=62) | After 14 days’ treatment, glycopyrrolate at doses 18, 9, 4.6, and 2.4 µg BID resulted in significant and clinically relevant improvements in FEV1 AUC0–12 compared with placebo (LSM difference from baseline 126–158 mL, P<0.0001) Glycopyrrolate 18 µg BID was noninferior to open-label tiotropium 18 µg QD for peak change in FEV1 on day 1 (LSM change from baseline 0.231 vs 0.270 L) and morning predose trough FEV1 on day 14 (LSM change from baseline 0.089 vs 0.126 L) and was the most appropriate dose for further evaluation |
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| Chronic-dosing, Phase IIB, incomplete block, crossover trial57 | 7 days | Glycopyrrolate (as glycopyrronium) 28.8, 14.4, 7.2, 3.6 µg BID (n=192), placebo BID (n=48), open-label ipratropium 34 µg QID (n=48)b | At day 7, all glycopyrrolate doses were superior to placebo for improvement from baseline in FEV1 AUC0–12 (LSM treatment differences vs placebo 0.121–0.191 L, all P<0.0001) All glycopyrrolate doses were noninferior to ipratropium (data not shown) Glycopyrrolate 28.8 and 14.4 µg were the most effective doses for improving all secondary efficacy end points |
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Notes:
a
Phase II studies included, as Phase III trial data have not yet been published for this product;
b
each patient received three treatments of two doses of glycopyrrolate and either placebo or ipratropium.
Abbreviations: AUC, area under curve; BID, bis in die (twice daily); FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; LSM, least squares mean; NS, not significant; QD, quaque die (once daily); QID, quater in die (four times daily); SGRQ, St George’s Respiratory Questionnaire; TDI, Transition Dyspnea Index.