PINNACLE-130
US, Australia, New Zealand |
Current or ex-smokers (≥10 pack-years) Age 40–80 years Moderate to very severe COPD Postbronchodilator FEV1 <80% FEV1/FVC <70% |
GFF pMDI 18/9.6 μg BID (n=526)
vs
GP pMDI 18 μg BID (n=451)
vs
FF pMDI 9.6 μg BID (n=449)
vs
OL tiotropium 18 μg QD (n=451)
vs
Placebo BID (n=219)
× 24 weeks
|
GFF, GP, and FF pMDI significantly improved predose morning trough FEV1 at week 24 vs placebo (all p<0.0001) GFF showed significant differences of 59 mL and 64 mL vs GP and FF, respectively GFF significantly improved 2-hour postdose change from baseline FEV1 at week 24 vs monocomponents (all p<0.0001) Across both studies, most common AEs were nasopharyngitis, cough, upper respiratory tract infection, sinusitis, dyspnea; all occurred with similar frequency in active vs placebo groups |
PINNACLE-230
US |
Same as above |
GFF pMDI 18/9.6 μg BID (n=510)
vs
GP pMDI 18 μg BID (n=439)
vs
FF pMDI 9.6 μg BID (n=437)
vs
Placebo BID (n=223)
× 24 weeks
|
GFF, GP, and FF pMDI significantly improved predose morning trough FEV1 at week 24 vs placebo (all p<0.02) GFF showed significant differences of 54 mL and 56 mL vs GP and FF, respectively GFF significantly improved 2-hour postdose change from baseline FEV1 at week 24 vs monocomponents (all p<0.0001) |
PINNACLE-331
US, Australia, New Zealand |
Extension study of PINNACLE-1, −2 Patients receiving GFF, GP, FF, or tiotropium were eligible to continue Patients receiving placebo were not eligible |
GFF pMDI 18/9.6 μg BID (n=1035)
vs
GP pMDI 18 μg BID (n=888)
vs
FF pMDI 9.6 μg BID (n=884)
vs
OL tiotropium 18 μg QD (n=450)
× 28 weeks
|
GFF pMDI significantly improved predose morning trough FEV1 over 52 weeks vs GP, FF, and tiotropium (p<0.0001 vs GP, FF and p=0.0117 vs tiotropium) GFF also significantly improved 2-hour postdose FEV1 over 52 weeks vs both monocomponents and tiotropium (all p<0.0001) Dyspnea scores improved significantly for GFF vs monocomponents No new safety risks were identified for GFF pMDI vs monocomponents |
PINNACLE-432
Asia, EU, US |
Same as PINNACLE-1 and −2 |
GFF pMDI 18/9.6 μg BID (n=555)
vs
GP pMDI 18 μg BID (n=480)
vs
FF pMDI 9.6 μg BID (n=483)
vs
Placebo BID (n=238)
× 24 weeks
|
GFF pMDI significantly improved predose morning trough FEV1 at week 24 vs GP, FF, and placebo (all p<0.0001) GFF significantly improved 2-hour postdose change from baseline FEV1 at week 24 vs monocomponents and placebo (all p<0.0001) Significant improvement in TDI over 24 weeks for GFF vs GP (LSM difference, 0.33; p=0.0125) and placebo (LSM difference, 0.80; p<0.001) GFF improved SGRQ total score vs placebo (LSM difference, −5.33; p=0.0011) |
AUGMENT34
North America, Australia, New Zealand |
|
ACL/FF DPI 400/12 μg BID (n=335)
vs
ACL/FF DPI 400/6 μg BID (n=333)
vs
ACL DPI 400 μg BID (n=337)
vs
FF DPI 12 μg BID (n=332)
vs
Placebo DPI (n=331)
× 24 weeks
|
Both doses of ACL/FF significantly improved 1-hour postdose FEV1 change from baseline to week 24 vs ACL (LSM difference, 108 mL and 87 mL, respectively p<0.0001) ACL/FF 400/12 μg significantly improved predose morning trough FEV1 from baseline to week 24 vs FF (LSM difference, 45 mL; p=0.01) Numerically greater improvements in FEV1 measurements were observed for the higher dose of ACL/FF vs the lower dose TDI focal scores were significantly improved with ACL/FF vs ACL, FF (p≤0.01), and placebo (p<0.0001) SGRQ total scores were significantly improved at week 24 for ACL/FF and monocomponents vs placebo (p<0.05) Most common AEs were cough and nasopharyngitis |
ACLIFORM-COPD35
EU, South Africa, South Korea |
|
ACL/FF DPI 400/12 μg BID (n=385)
vs
ACL/FF DPI 400/6 μg BID (n=381)
vs
ACL DPI 400 μg BID (n=385)
vs
FF DPI 12 μg BID (n=384)
vs
Placebo DPI (n=194)
× 24 weeks
|
Both doses of ACL/FF significantly improved 1-hour postdose FEV1 change from baseline to week 24 vs ACL and FF (p<0.001), with the 400/12 μg dose superior to the 400/6 μg dose TDI focal scores improved above 1-unit threshold for both doses of ACL/FF (1.29 and 1.16) Incidences of AEs were similar across combination, monotherapy, and placebo arms |
AFFIRM-COPD25
EU, Canada, South Africa |
|
ACL/FF DPI 400/12 μg BID (n=468)
vs
Salmeterol/fluticasone DPI 50/500 μg BID (n=463)
× 24 weeks
|
Peak FEV1 was significantly greater with ACL/FF vs salmeterol/fluticasone at week 24, with significant differences observed after first dose (p<0.0001) Mean increase in peak FEV1 at week 24 was 93 mL greater with ACL/FF No significant differences in changes in TDI scores, CAT total scores, or exacerbations between groups Most common AEs were COPD exacerbation, headache, and nasopharyngitis and were similar between groups |
AMPLIFY39
EU, Israel, US |
|
ACL/FF DPI 400/12 μg BID (n=314)
vs
ACL DPI 400 μg BID (n=475)
vs
FF DPI 12 μg BID (n=319)
vs
Tiotropium DPI 18 μg QD (n=475)
× 24 weeks
|
ACL/FF significantly improved 1-hour postdose FEV1 from baseline at week 24 vs ACL, FF, and tiotropium (all p<0.0001) ACL/FF significantly improved predose morning trough FEV1 vs FF (p<0.001) SGRQ total score improved vs baseline >MCID for ACL/FF (4.68), ACL (4.95), and tiotropium (5.58); improvement for FF was 3.96 Early morning symptom severity was significantly improved with ACL/FF vs tiotropium (p<0.05) Most common AEs: COPD exacerbation, nasopharyngitis, and headache |
