TABLE 3.
UP0077 (phase 1b study in participants with PD) pharmacokinetic parameters of UCB0599 and its metabolites
| 180 mg/day dose, n = 7 | 360 mg/day dose, n = 14 | |||||||
|---|---|---|---|---|---|---|---|---|
| Statistics | Day | UCB0599 | Desmethyl metabolite | N‐oxide metabolite | UCB0599 | Desmethyl metabolite | N‐oxide metabolite | |
| AUC (h*ng/mL) | Geometric mean (CV%) | 1 | 2233 (27.8) | 77.01 (55.6) | 2170 (42.1) | 3387 (48.7) | 78.49 (50.7) | 2359 (43.9) |
| 28 | 3736 (42.3) | 184.6 (67.1) | 3914 (48.4) | 7652 (28.1) a | 315.5 (55.2) a | 5777 (38.8) a | ||
| C max (ng/mL) | Geometric mean (CV%) | 1 | 417.3 (36.6) | 10.22 (48.2) | 287.9 (40.3) | 662.1 (53.0) | 11.56 (51.2) | 320.8 (36.1) |
| 28 | 670.8 (43.1) | 22.15 (65.2) | 501.9 (45.2) | 1273 (33.4) a | 34.34 (58.1) a | 652.2 (41.7) a | ||
| t max (h) | Median (range) | 1 | 2.0 (1.0–2.85) | 1.980 (1.0–8.0) | 3.00 (1.8–4.0) | 2.0 (1.0–6.13) | 2.0 (0.5–7.9) | 3.0 (1.0–7.9) |
| 28 | 2.0 (1.5–4.0) | 1.550 (1.0–4.0) | 2.750 (1.5–4.0) | 2.0 (1.0–6.12) a | 1.6 (1.0–8.0) a | 3.1 (1.5–8.0) a | ||
| Half‐life (h) | Geometric mean (CV%) | 28 | 10.73 (32.8) | 15.11 (26.4) | 13.84 (43.5) | 13.08 (23.9) a | 18.70 (22.7) a | 13.84 (27.7) a |
| Fraction unbound (%) | Geometric mean (CV%) | 1 | 1.1 (31.0) | – | – | 1.0 (32.2) a | – | – |
| 28 | 1.2 (37.1) | 1.0 (25.4) b | ||||||
The PK of multiple doses of UCB0599 were predictable from single‐dose exposures. C max and AUC demonstrated dose‐proportional increases, and UCB0599 fraction unbound was constant between dose groups.
Abbreviations: PD, Parkinson's disease; AUC, area under the plasma concentration–time curve from 0 to 12 hours (day 1) and for the dosing interval at steady state (day 28); C max, maximum plasma concentration; CV, coefficient of variation; t max, time of maximum concentration; PK, pharmacokinetic.
a
n = 13 for these PK parameters.
b
n = 10 for this PK parameter. PK‐per protocol set.