Table 3.
Key secondary endpoints, COPD Proof of Principle study
| Secondary endpoint | AZD7624 1.0 mg (n=107a)
|
Placebo (n=105)
|
AZD7624 vs placebo
|
|---|---|---|---|
| Change from baseline | Change from baseline | p-valueb | |
| Number of ExDo events | 40 | 29 | 0.25 |
| Number of moderate or severe exacerbations | 38 | 24 | 0.13 |
| Number of moderate or severe exacerbations according to Anthonisen criteria fulfilled | 17 | 15 | 0.75 |
| Number of symptom-defined exacerbations as defined by EXACT daily dairy | 42 | 50 | 0.44 |
| Post-bronchodilator FEV1 (L) | −0.003 (0.26) | −0.03 (0.23) | 0.51 |
| Post-bronchodilator FVC (L) | −0.045 (0.40) | −0.018 (0.39) | 0.05 |
| FEV1/FVC | 0.04 (0.06) | −0.007 (0.05) | 0.15 |
| SGRQ-C | −4.0 (19.6) | −5.1 (17.8) | 0.52 |
| TDI | 1.6 (3.2) | 1.7 (3.2) | 0.49 |
| EXACT E-RS | −0.2 (6.4) | −0.2 (6.3) | 0.55 |
| Use of reliever medication (average puffs per day) | −0.13 (2.27) | −0.29 (2.12) | 0.22 |
| Night-time awakenings (% of days during a 2-week period) | −8.98 (32.53) | −11.65 (33.90) | 0.66 |
|
| |||
| Secondary endpoint |
AZD7624 (n=107a) vs placebo (n=105)
|
||
| HR | 95% CI | p-valueb | |
|
| |||
| Time to first moderate or severe exacerbations according to Anthonisen criteria fulfilled | 0.93 | 0.43, 2.01 | 0.85 |
| Time to symptom-defined exacerbations as defined by EXACT daily dairy | 0.86 | 0.54, 1.38 | 0.54 |
Notes:
One patient was excluded from the analysis following a review of protocol deviations owing to a lack of source data and Good Clinical Practice compliance.
Mixed-effects repeated measures analysis, fitting treatment, country, LAMA maintenance treatment, visit, gender, smoking history, and treatment by visit interaction as fixed effects; patient as a random effect; and baseline assessment, age, BMI, and height as continuous covariates.
Abbreviations: BMI, body mass index; E-RS, Evaluating Respiratory Symptoms; ExDo, time to first event of moderate or severe COPD exacerbations or early dropout related to worsening of COPD symptoms; EXACT, EXAcerbations of Chronic pulmonary disease Tool; LAMA, long-acting muscarinic antagonist; SGRQ-C, St George’s Respiratory Questionnaire for COPD Patients; TDI, Transition Dyspnea Index.