Table 2.
Primary, Key Secondary, and Additional Endpoint Results in ENHANCE-1 and ENHANCE-2 Trials (mITT Population)
| Treatment Group | ENHANCE-1 |
ENHANCE-2 |
||
|---|---|---|---|---|
| Ensifentrine 3 mg BID (n = 477) | Placebo BID (n = 283) | Ensifentrine 3 mg BID (n = 498) | Placebo BID (n = 291) | |
| Primary endpoint | ||||
| Mean baseline FEV1, ml (SD) | 1,420 (487) | 1,403 (468) | 1,285 (451) | 1,279 (473) |
| Week 12 average FEV1 AUC0–12 h | ||||
| LS mean change from baseline, ml (95% CI) | 61 (25, 97) | −26 (−64, 13) | 48 (30, 66) | −46 (−70, −22) |
| Ensifentrine vs. placebo, ml (95% CI) | 87 (55, 119) | — | 94 (65, 124) | — |
| P value | <0.001 | — | <0.001 | — |
| Key secondary endpoints | ||||
| Week 12 peak FEV1 | ||||
| LS mean change from baseline, ml (95% CI) | 204 (165, 244) | 57 (15, 100) | 195 (175, 214) | 48 (22, 75) |
| Ensifentrine vs. placebo, ml (95% CI) | 147 (111, 183) | — | 146 (113, 179) | — |
| P value | <0.001 | — | <0.001 | — |
| Week 12 morning trough FEV1 | ||||
| LS mean change from baseline, ml (95% CI) | 8 (−30, 45) | −27 (−67, 13) | 6 (−13, 24) | −44 (−68, −19) |
| Ensifentrine vs. placebo, ml (95% CI) | 35 (1, 68) | — | 49 (19, 80) | — |
| P value | 0.041 | — | 0.002 | — |
| Week 24 E-RS total score | ||||
| Mean baseline (SD) | 14.1 (6.8) | 13.3 (6.1) | 13.3 (6.7) | 13.3 (6.2) |
| LS mean change from baseline (95% CI) | −2.2 (−3.1, −1.4) | −1.3 (−2.2, −0.4) | −2.1 (−2.6, −1.6) | −1.5 (−2.2, −0.9) |
| Ensifentrine vs. placebo (95% CI) | −1.0 (−1.7, −0.2) | — | −0.6 (−1.4, 0.2) | — |
| P value | 0.011 | — | 0.134 | — |
| Week 24 SGRQ total score | ||||
| Mean baseline (SD) | 48.1 (18.3) | 46.9 (17.1) | 50.6 (17.4) | 51.2 (16.4) |
| LS mean change from baseline (95% CI) | −6.2 (−8.4, −3.9) | −3.9 (−6.3, −1.5) | −4.5 (−5.9, −3.2) | −4.1 (−5.8, −2.3) |
| Ensifentrine vs. placebo (95% CI) | −2.3 (−4.3, −0.3) | — | −0.5 (−2.7, 1.7) | — |
| P value | 0.025 | — | 0.669 | — |
| Additional endpoints | ||||
| Week 24 average daily rescue medication use over 7 d | ||||
| Mean baseline (SD) | 1.54 (2.40) | 1.52 (2.23) | 1.86 (2.35) | 1.93 (2.43) |
| LS mean change from baseline (95% CI) | −0.51 (−0.79, −0.22) | −0.05 (−0.36, 0.25) | −0.49 (−0.66, −0.31) | −0.35 (−0.57, −0.12) |
| Ensifentrine vs. placebo (95% CI) | −0.45 (−0.70, −0.20) | — | −0.14 (−0.41, 0.14) | — |
| P value | <0.001 | — | 0.320 | — |
| Week 24 TDI | ||||
| Mean baseline (SD) | 5.9 (1.1) | 5.9 (1.1) | 5.9 (1.3) | 5.9 (1.2) |
| LS mean change from baseline (95% CI) | 1.9 (1.4, 2.3) | 0.8 (0.3, 1.4) | 2.2 (1.9, 2.5) | 1.3 (0.9, 1.7) |
| Ensifentrine vs. placebo (95% CI) | 1.0 (0.6, 1.5) | — | 0.9 (0.4, 1.4) | — |
| P value | <0.001 | — | <0.001 | — |
Definition of abbreviations: AUC = area under the curve; BID = twice daily; CI = confidence interval; E-RS = Evaluating-Respiratory Symptoms; LS = least squares; mITT = modified intention-to-treat; SGRQ = St. George’s Respiratory Questionnaire; SD = standard deviation; TDI = Transition Dyspnea Index.
Average FEV1 AUC0–12 h is defined as the AUC over 12 hours of the FEV1, divided by 12 hours. Peak FEV1 is defined as the maximum value in the 4 hours after dosing. Morning trough FEV1 is defined as the last value collected before the morning dose. Primary and key secondary endpoints were compared using an analysis of covariance model adjusting for treatment, region (North America, Europe, Asia [ENHANCE-1 only]), background medication strata (yes, no), and smoking status (current, former) as factors and baseline as the covariate.