Background
Methods
Study design and treatment
Patients
Objectives and endpoints
Assessments
Statistical analysis
Post-hoc analysis of pooled data
Results
Patients
PT003011 | PT003012 | ||||
---|---|---|---|---|---|
GFF MDI 18/9.6 μg (n = 73) | Placebo MDI (n = 69) | TIO SMI 5 μg (n = 73) | GFF MDI 18/9.6 μg (n = 35) | Placebo MDI (n = 35) | |
Mean age, years (SD) | 61.9 (9.1) | 61.7 (9.1) | 61.9 (8.9) | 61.3 (9.2) | 61.3 (9.2) |
Male, n (%) | 26 (35.6) | 24 (34.8) | 27 (37.0) | 20 (57.1) | 20 (57.1) |
White, n (%) | 66 (90.4) | 63 (91.3) | 66 (90.4) | 27 (77.1) | 27 (77.1) |
Current smokers, n (%) | 45 (61.6) | 43 (62.3) | 45 (61.6) | 20 (57.1) | 20 (57.1) |
Mean smoking history, pack-years (SD) | 56.4 (29.2) | 57.6 (29.3) | 55.9 (29.3) | 49.0 (25.2) | 49.0 (25.2) |
Use of ICS at baseline, n (%) | 23 (31.5) | 20 (29.0) | 22 (30.1) | 10 (28.6) | 10 (28.6) |
COPD severity, n (%) | |||||
Moderate | 53 (72.6) | 47 (68.1) | 51 (69.9) | 20 (57.1) | 20 (57.1) |
Severe | 20 (27.4) | 22 (31.9) | 22 (30.1) | 14 (40.0) | 14 (40.0) |
Very severe | 0 | 0 | 0 | 1 (2.9) | 1 (2.9) |
Mean COPD duration, years (SD) | 6.8 (5.9) | 7.2 (6.1) | 7.1 (6.0) | 6.3 (4.7) | 6.3 (4.7) |
Mean pre-bronchodilator FEV1
| |||||
mL (SD) | 1410 (461) | 1396 (466) | 1414 (460) | 1406 (542) | 1406 (542) |
% predicted (SD) | 52.54 (13.97) | 51.70 (14.20) | 52.33 (14.11) | 48.34 (16.20) | 48.34 (16.20) |
Mean post-bronchodilator FEV1
| |||||
mL (SD) | 1542 (435) | 1521 (434) | 1546 (434) | 1525 (538) | 1525 (538) |
% predicted (SD) | 57.69 (13.50) | 56.61 (13.61) | 57.44 (13.68) | 52.51 (15.35) | 52.51 (15.35) |
Baseline ICa, mL (SD) | 1877 (527) | 1913 (560) | 1925 (546) | 1979 (656) | 1942 (632) |
Average daily rescue medication use at baselineb, puffs/day (SD) | 2.5 (3.5) | 2.6 (3.7) | 2.6 (3.6) | 3.4 (3.4) | 3.4 (3.4) |
Patients with a moderate or severe COPD exacerbationc within the past 12 monthsd, n (%) | 13 (17.3) | 12 (16.7) | 12 (16.4) | 10 (25.0) | 10 (25.0) |
Patients hospitalized/ER room treatment within the past 12 monthsd, n (%) | 4 (5.3) | 5 (6.9) | 5 (6.8) | 0 | 0 |
Efficacy
PT003011 | PT003012 | ||||
---|---|---|---|---|---|
GFF MDI 18/9.6 μg | Placebo MDI | TIO SMI 5 μg | GFF MDI 18/9.6 μg | Placebo MDI | |
n = 65 |
n = 65 |
n = 67 |
n = 35 |
n = 31 | |
FEV1 AUC12–24 (mL) on day 29, LSM (SE) | 159 (27.7) | −118 (27.7) | 39 (27.5) | 115 (29.9) | −127 (32.0) |
Treatment difference GFF MDI vs comparator LSM (95% CI)
| NA | 277 (232–321) | 120 (76–164) | NA | 242 (165–319) |
n = 67 |
n = 66 |
n = 68 |
n = 35 |
n = 31 | |
FEV1 AUC0–12 (mL) on day 29, LSM (SE) | 226 (25.7) | −26 (25.8) | 178 (25.6) | 216 (29.8) | −39 (31.8) |
Treatment difference GFF MDI vs comparator LSM (95% CI)
| NA | 251 (207–296) | 48 (4–92) | NA | 255 (182–329) |
n = 65 |
n = 65 |
n = 67 |
n = 35 |
n = 31 | |
Peak change from baseline in FEV1 (mL) following evening dose on day 29, LSM (SE) | 395 (30.9) | 58 (31) | 230 (30.7) | 344 (34.2) | 50 (36.6) |
Treatment difference GFF MDI vs comparator LSM (95% CI)
| NA | 337 (282–392) | 165 (110–219) | NA | 293 (204–382) |
n = 67 |
n = 67 |
n = 68 |
n = 35 |
n = 31 | |
Peak change from baseline in FEV1 (mL) following morning dose on day 29, LSM (SE) | 406 (28.3) | 129 (28.3) | 325 (28.1) | 410 (35.8) | 134 (37.6) |
Treatment difference GFF MDI vs comparator LSM (95% CI)
| NA | 278 (225–330) | 81 (29–133) | NA | 276 (206–347) |
n = 67 |
n = 66 |
n = 68 |
n = 35 |
n = 32 | |
Change from baseline in morning pre-dose trough FEV1 on day 29 (mL), LSM (SE) | 140 (22.7) | −20 (22.9) | 97 (22.5) | 130 (21.7) | −12 (22.7) |
Treatment difference GFF MDI vs comparator LSM (95% CI)
| NA | 161 (106–215) | 43 (−11–97) | NA | 142 (90–194) |
n = 66 |
n = 66 |
n = 66 |
n = 35 |
n = 31 | |
Change from baseline in morning pre-dose trough FEV1 on day 30 (mL), LSM (SE) | 129 (28.4) | −73 (28.4) | 72 (28.3) | 90 (28.8) | −64 (30.2) |
Treatment difference GFF MDI vs comparator LSM (95% CI)
| NA | 203 (153–252) | 58 (8–108) | NA | 154 (97–211) |
Post-hoc analysis of pooled data
Response in peak IC | Treatment versus comparator, OR (95% CI) | |||||
---|---|---|---|---|---|---|
GFF MDI 18/9.6 μg
n = 102 | Placebo MDI
n = 99 | TIO SMI 5 μg
n = 68 | GFF MDI vs placebo MDI | GFF MDI vs TIO SMI | TIO SMI vs placebo MDI | |
Patients achieving a response (evening), % | ||||||
> 10% | 83.5 | 31.5 | 71.1 | 11.00 (4.12–29.43) | 2.05 (0.83–5.10) | 5.36 (2.13–13.49) |
> 15% | 72.1 | 19.0 | 47.0 | 10.98 (4.34–27.79) | 2.91 (1.27–6.68) | 3.77 (1.58–8.98) |
> 20% | 54.8 | 15.3 | 31.4 | 6.70 (2.98–15.08) | 2.65 (1.27–5.51) | 2.53 (1.12–5.74) |
> 200 mL | 83.1 | 27.8 | 61.3 | 12.78 (4.70–34.79) | 3.12 (1.25–7.79) | 4.10 (1.68–9.99) |
> 300 mL | 66.3 | 20.0 | 43.4 | 7.84 (3.47–17.74) | 2.56 (1.22–5.37) | 3.06 (1.38–6.79) |
> 400 mL | 46.5 | 10.3 | 20.9 | 7.58 (3.09–18.63) | 3.29 (1.42–7.61) | 2.31 (0.89–5.96) |
Patients achieving a response (morning), % | ||||||
> 10% | 92.1 | 47.2 | 75.2 | 12.94 (4.57–36.68) | 3.82 (1.38–10.57) | 3.39 (1.39–8.30) |
> 15% | 81.4 | 30.1 | 65.5 | 10.16 (4.11–25.14) | 2.31 (0.98–5.46) | 4.39 (1.85–10.44) |
> 20% | 75.6 | 12.5 | 46.8 | 21.72 (6.58–71.65) | 3.53 (1.32–9.47) | 6.15 (2.06–18.35) |
> 200 mL | 89.5 | 40.7 | 72.8 | 12.37 (4.82–31.78) | 3.17 (1.27–7.94) | 3.90 (1.70–8.95) |
> 300 mL | 79.1 | 23.6 | 67.4 | 12.24 (4.62–32.47) | 1.83 (0.75–4.45) | 6.69 (2.51–17.80) |
> 400 mL | 67.9 | 13.3 | 34.0 | 13.84 (5.24–36.54) | 4.12 (1.77–9.60) | 3.36 (1.33–8.51) |
Safety and tolerability
PT003011 | PT003012 | ||||
---|---|---|---|---|---|
GFF MDI 18/9.6 μg (n = 75) | Placebo MDI (n = 72) | TIO SMI 5 μg (n = 73) | GFF MDI 18/9.6 μg (n = 40) | Placebo MDI (n = 40) | |
Patients with ≥1 TEAE | 19 (25.3) | 15 (20.8) | 16 (21.9) | 7 (17.5) | 10 (25.0) |
Patients with ≥1 treatment-related TEAE | 7 (9.3) | 4 (5.6) | 3 (4.1) | 0 | 1 (2.5) |
Patients with ≥1 serious TEAE | 2 (2.7) | 2 (2.8) | 2 (2.7) | 1 (2.5) | 1 (2.5) |
Patients with TEAEs leading to study discontinuation | 3 (4.0) | 1 (1.4) | 1 (1.4) | 1 (2.5) | 1 (2.5) |
Adverse events occurring in ≥2 patients in any group | |||||
Respiratory, thoracic, and mediastinal disorders | 2 (2.7) | 4 (5.6) | 3 (4.1) | 0 | 5 (12.5) |
Dyspnea | 0 | 0 | 1 (1.4) | 0 | 2 (5.0) |
Sinus congestion | 0 | 0 | 0 | 0 | 2 (5.0) |
Cough | 1 (1.3) | 2 (2.8) | 1 (1.4) | 0 | 1 (2.5) |
Infections and infestations | 6 (8.0) | 2 (2.8) | 4 (5.5) | 3 (7.5) | 2 (5.0) |
Furuncle | 0 | 0 | 2 (2.7) | 0 | 0 |
Vascular disorders | 0 | 0 | 0 | 1 (2.5) | 3 (7.5) |
Hypertension | 0 | 0 | 0 | 1 (2.5) | 2 (5.0) |
Gastrointestinal disorders | 5 (6.7) | 4 (5.6) | 5 (6.8) | 0 | 0 |
Constipation | 2 (2.7) | 1 (1.4) | 0 | 0 | 0 |
Vomiting | 0 | 0 | 3 (4.1) | 0 | 0 |
Nervous system disorders | 4 (5.3) | 2 (2.8) | 2 (2.7) | 0 | 0 |
Headache | 1 (1.3) | 2 (2.8) | 1 (1.4) | 0 | 0 |
Tremor | 3 (4.0) | 0 | 0 | 0 | 0 |
Musculoskeletal and connective tissue disorders | 2 (2.7) | 2 (2.8) | 0 | 0 | 0 |
Back pain | 1 (1.3) | 2 (2.8) | 0 | 0 | 0 |