Table 5.
Pharmacodynamic measures - Regimen B: treatment medians and treatment contrasts
| Untransformed pre-dose morning values | ||||||||
|---|---|---|---|---|---|---|---|---|
| Median | Point estimate (95% CI) | |||||||
| Variable | Day 1 | Day 8 (F) | Day 18 (F+R) | Day 8-Day 1 | Day 18-Day 8 | Day 18-Day 1 | ||
| HR (bpm) | 58 | 66 | 62 | 5 (2 to 9) | -1 (-4 to 3) | 4 (2 to 7) | ||
| PEP (ms) | 105 | 97 | 98 | -7 (-22 to 7) | 3 (-9 to 17) | -5 (-19 to 20) | ||
| QS2 (ms) | 434 | 431 | 445 | -4 (-18 to 9) | 4 (-7 to 13) | 2 (-13 to 16) | ||
| dZ/dt (Ω/s) | 1.81 | 1.94 | 1.82 | 0.06 (-0.07 to 0.19) | -0.08 (-0.37 to 0.07) | -0.03 (-0.30 to 0.16) | ||
| CO (L/min) | 9.7 | 9.7 | 10.3 | 0.7 (-0.9 to 2.0) | -0.5 (-1.7 to 0.6) | 0.3 (-1.7 to 2.1) | ||
| TPR (dyn.s.cm-5) | 657 | 668 | 709 | -18 (-198 to 70) | 28 (-80 to 100) | -36 (-186 to 105) | ||
| Untransformed post-dose maximum and minimum values | ||||||||
| dmax (U) | dmin (U) | |||||||
| Median | Point estimate (95% CI) | Median | Point estimate (95% CI) | |||||
| Variable | Day 1 | Day 8 (F) | Day 18 (F+R) | Day 8-Day 1 | Day 1 | Day 8 (F) | Day 18 (F+R) | Day 8-Day 1 |
| HR (bpm) | 62 | 72 | 72 | 9 (5 to 11) | 51 | 62 | 60 | 7 (3 to 10) |
| PEP (ms) | 122 | 117 | 116 | -4 (-14 to 2) | 87 | 84 | 85 | 0 (-7 to 6) |
| QS2 (ms) | 459 | 440 | 445 | -14 (-27 to 4) | 424 | 408 | 410 | -13 (-22 to -3) |
| dZ/dt (Ω/s) | 2.05 | 2.10 | 2.20 | 0.01 (-0.15 to 0.21) | 1.53 | 1.64 | 1.60 | 0.03 (-0.13 to 0.17) |
| CO (L/min) | 9.8 | 11.8 | 11.8 | 1.7 (0.6 to 2.6) | 8.4 | 8.2 | 8.0 | 0.5 (-0.5 to 1.4) |
| TPR (dyn.s.cm-5) | 870 | 882 | 865 | -49 (-160 to 80) | 655 | 561 | 556 | -96 (-188 to -24) |
| Day 1-matched post-dose maximum and minimum values | ||||||||
| dmax (δ) | dmin (δ) | |||||||
| Median | Point estimate (95% CI) | Median | Point estimate (95% CI) | |||||
| Variable | Day 8 (F) | Day 18 (F+R) | Day 18-Day 8 | Day 8 (F) | Day 18 (F+R) | Day 18-Day 8 | ||
| HR (bpm) | 16 | 14 | -2 (-6 to 2) | -2 | -3 | -1 (-2 to 1) | ||
| PEP (ms) | 25 | 21 | 3 (-19 to 4) | -26 | -25 | 0 (-4 to 4) | ||
| QS2 (ms) | 13 | 15 | 4 (-7 to 13) | -47 | -37 | 8 (-1 to 15) | ||
| dZ/dt (Ω/s) | 0.32 | 0.28 | 0.05 (-0.16 to 0.17) | -0.29 | -0.37 | -0.05 (-0.27 to 0.15) | ||
| CO (L/min) | 2.9 | 3.3 | 0.0 (-1.0 to 1.5) | -0.6 | -0.6 | -0.4 (-1.3 to 0.6) | ||
| TPR (dyn.s.cm-5) | 61 | 66 | -18 (-95 to 73) | -221 | -224 | -42 (-107 to 35) | ||
CO, cardiac output; dmax, post-dose maximum values; dmin, post-dose minimum values; dZ/dt, rate of change of the transthoracic impedance; HR, heart rate; PEP, pre-ejection period; QS2, total electromechanic systole; TPR, total peripheral resistance.
Medians for baseline (Day 1), formoterol alone (F; Day 8) and formoterol plus roflumilast (F+R; Day 18) with the corresponding point and 95% confidence interval (CI) estimates for untransformed (U) morning pre-dose values, untransformed post-dose maximum and minimum values (dmax and dmin), and Day 1-matched (δ) post-dose maximum and minimum values.