Table 1.
Overview of the Study Design and Outcomes of the GOLDEN Phase 3 Clinical Trials.
| Phase 3 Study | Study Design | Treatments | Patient Population | Outcomes |
|---|---|---|---|---|
| GOLDEN 337 | 12-Week, double-blind, placebo-controlled | • Nebulized GLY 25 or 50 µg bid • Placebo |
Total n = 653 • GLY 25 µg bid (n = 217) • GLY 50 µg bid (n = 218) • Placebo (n = 218) |
Efficacy: • Clinically important improvements in placebo-adjusted change from baseline in trough FEV1 at week 12 (0.105L*** and 0.126 L*** with GLY 25 and 50 µg bid, respectively) • Clinically important improvements in placebo-adjusted change from baseline in trough FVC at week 12 (0.149 L*** and 0.167 L*** with GLY 25 and 50 µg bid, respectively) • Statistically significant improvement in placebo-adjusted SGRQ total score with GLY 25 µg bid (−3.072 units*); change in SGRQ with GLY 50 µg bid (−1.848 units) was not statistically significant Safety: • Frequency of TEAEs was highest in patients receiving placebo (52.3%) compared with GLY 25 and 50 µg bid (39.6% and 48.2%, respectively) • The most common TEAEs were cough (placebo: 10.1%; GLY 25 µg: 7.4%; GLY 50 µg: 9.6%) and worsening of COPD (placebo: 8.3%; GLY 25 µg: 5.1%; GLY 50 µg: 10.6%). Dry mouth occurred in 1.4% and 2.3% of patients receiving GLY 25 and 50 µg, respectively, but not in patients receiving placebo • Discontinuations resulting from AEs were more common with placebo (9.6%) compared with GLY 25 and 50 µg bid (3.2% and 3.7%, respectively) |
| GOLDEN 437 | 12-Week, double-blind, placebo-controlled | • Nebulized GLY 25 or 50 µg bid • Placebo |
Total n = 640 • GLY 25 µg bid (n = 214) • GLY 50 µg bid (n = 214) • Placebo (n = 212) |
Efficacy: • Clinically important improvements in placebo-adjusted change from baseline in trough FEV1 at week 12 (0.084 L*** and 0.082 L*** with GLY 25 and 50 µg bid, respectively) • Clinically important improvements in placebo-adjusted change from baseline in trough FVC at week 12 (0.130 L*** and 0.113 L** with GLY 25 and 50 µg bid, respectively) • Statistically significant improvement in placebo-adjusted SGRQ total score with GLY 25 and 50 µg bid (−3.59** and −3.56** units, respectively) Safety: • Frequency of TEAEs was similar in patients receiving placebo (52.4%) and GLY 50 µg bid (53.3%) and lowest with GLY 25 µg bid (47.2%) • The most common TEAEs were cough (placebo: 6.6%; GLY 25 µg: 6.5%; GLY 50 µg: 8.4%), worsening of COPD (placebo: 9.0%; GLY 25 µg: 7.9%; GLY 50 µg: 6.5%), and dyspnea (placebo: 3.8%; GLY 25 µg: 7.5%; GLY 50 µg: 5.1%). Dry mouth occurred in 0.5%, 0.5%, and 0.9% of patients receiving placebo, GLY 25 µg, and GLY 50 µg, respectively • Discontinuations resulting from TEAEs were more common with placebo (9.0%) compared with GLY 25 and 50 µg bid (7.0% and 4.2%, respectively) |
| GOLDEN 536 | 48-Week, open-label, active-controlled, long-term safety study | • Nebulized GLY 50 µg bid • TIO 18 µg qd DPI |
Total n = 1086 • GLY (n = 620) • TIO (n = 466) |
Efficacy: • Sustained improvement in LSM change from baseline in trough FEV1 over 48 weeks of 0.102 L with GLY 50 µg bid compared with 0.093 L with TIO 18 µg qd • Similar improvements in placebo-adjusted change from baseline in trough FEV1 at week 48 (0.069 and 0.089 L with GLY 50 µg bid and TIO 18 µg qd, respectively) • Similar improvement in placebo-adjusted SGRQ total score with GLY 50 µg bid (−3.07 units) and TIO 18 µg qd (−4.08 units) at week 48 Safety: • Frequency of TEAEs was similar between treatments over 48 weeks (69.4% and 67.0% with GLY 50 µg bid and TIO 18 µg qd, respectively) • Discontinuations resulting from TEAEs were more common with GLY 50 µg bid (10.0%) compared with TIO 18 µg qd (2.8%) • Incidence of CV disease among patients receiving either treatment was similar regardless of their CV risk (high risk: 4.7% and 4.4%; low risk: 2.3% and 3.6%; with GLY 50 µg bid and TIO 18 µg qd, respectively) |
Abbreviations: AE, adverse event; bid, twice daily; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; DPI, dry powder inhaler; FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; GLY, glycopyrrolate; GOLDEN, Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer; LSM, least squares mean; qd, once daily; SGRQ, St George’s Respiratory Questionnaire; TEAE, treatment-emergent adverse event; TIO, tiotropium.
*
P < 0.05, **P < 0.01, ***P < 0.001 versus placebo.