FIGURE 1.
FIGURE 2
FIGURE 3.
PK metrics and food effect assessment – DEX-MR 10 mg (20 mg dose) and DEX-MR 20 mg (single-dose study), 28 subjects_
| PK metric (unit) | Geometric Least Squares Mean | PE (%) | 90% CI | CVintra (%) | CVinter (%) | |
|---|---|---|---|---|---|---|
| DEX-MR 10 mg (1×2) | ||||||
| fasting | fed | |||||
| Cmax (ng/mL) | 53.94 | 48.67 | 110.83 | 105.56 – 116.26 | 10.39 | 11.35 |
| AUC0–t (h×ng/mL) | 914.8 | 816.6 | 112.02 | 107.91 – 116.29 | 8.12 | 14.56 |
| AUC0–∞ (h×ng/mL) | 926.2 | 825.5 | 112.20 | 107.93 – 116.63 | 8.41 | 14.56 |
| DEX-MR 20 mg (1×1) | ||||||
| fasting | fed | |||||
| Cmax (ng/mL) | 53.98 | 47.53 | 113.58 | 107.45 – 120.05 | 12.06 | 10.23 |
| AUC0–t (h×ng/mL) | 871.8 | 817.8 | 106.61 | 102.43 – 110.96 | 8.68 | 11.59 |
| AUC0–∞ (h×ng/mL) | 882.0 | 828.7 | 106.44 | 102.16 – 110.89 | 8.91 | 11.78 |
Comparative bioavailabilities of DEX-MR (20 mg dose) and DEX-IR 10 mg b_i_d_ under fasted and fed conditions (single-dose study), 28 subjects_
| PK metric (unit) | Geometric Least Squares Mean | PE (%) | 90% CI | CVintra (%) | CVinter (%) | |
|---|---|---|---|---|---|---|
| Fasted conditions | ||||||
| DEX-MR 10 mg 1×2 | DEX-IR 10 mg b.i.d. | |||||
| Cmax (ng/mL) | 53.94 | 57.82 | 93.29 | 91.26 – 95.36 | 4.78 | 12.40 |
| AUC0–t (h×ng/mL) | 914.8 | 884.4 | 103.43 | 99.81 – 107.18 | 7.75 | 15.11 |
| AUC0–∞ (h×ng/mL) | 926.2 | 895.6 | 103.41 | 99.66 – 107.30 | 8.03 | 15.39 |
| DEX-MR 20 mg 1×1 | DEX-IR 10 mg b.i.d. | |||||
| Cmax (ng/mL) | 53.98 | 57.82 | 93.35 | 90.71 – 96.08 | 6.24 | 10.25 |
| AUC0–t (h×ng/mL) | 871.8 | 884.4 | 98.57 | 95.91 – 101.31 | 5.94 | 16.16 |
| AUC0–∞ (h×ng/mL) | 882.0 | 895.6 | 98.48 | 95.77 – 101.27 | 6.06 | 16.66 |
| DEX-MR 10 mg 1×2 | DEX-MR 20 mg 1×1 | |||||
| Cmax (ng/mL) | 53.94 | 53.97 | 99.95 | 97.15 – 102.82 | 6.18 | 11.26 |
| AUC0–t (h×ng/mL) | 914.3 | 872.2 | 104.82 | 101.94 – 107.79 | 6.09 | 15.22 |
| AUC0–∞ (h×ng/mL) | 925.7 | 882.5 | 104.90 | 101.91 – 107.98 | 6.31 | 15.51 |
| Fed conditions | ||||||
| DEX-MR 10 mg 1×2 | DEX-IR 10 mg b.i.d. | |||||
| Cmax (ng/mL) | 48.67 | 57.00 | 85.38 | 81.25 – 89.72 | 10.80 | 9.39 |
| AUC0–t (h×ng/mL) | 816.6 | 821.2 | 99.44 | 96.20 – 102.80 | 7.21 | 13.89 |
| AUC0–∞ (h×ng/mL) | 825.5 | 831.5 | 99.28 | 95.98 – 102.70 | 7.35 | 14.02 |
| DEX-MR 20 mg 1×1 | DEX-IR 10 mg b.i.d. | |||||
| Cmax (ng/mL) | 47.53 | 57.00 | 83.37 | 79.06 – 87.92 | 11.55 | 10.88 |
| AUC0–t (h×ng/mL) | 817.8 | 821.2 | 99.59 | 96.44 – 102.84 | 6.97 | 11.04 |
| AUC0–∞ (h×ng/mL) | 828.7 | 831.5 | 99.66 | 96.44 – 103.00 | 7.14 | 11.01 |
| DEX-MR 10 mg 1×2 | DEX-MR 20 mg 1×1 | |||||
| Cmax (ng/mL) | 48.59 | 47.61 | 102.06 | 95.66 – 108.51 | 13.42 | 12.19 |
| AUC0–t (h×ng/mL) | 816.0 | 818.4 | 99.71 | 95.84 – 103.73 | 8.63 | 12.11 |
| AUC0–∞ (h×ng/mL) | 824.9 | 829.3 | 99.47 | 95.48 – 103.62 | 8.93 | 12.07 |
Comparative bioavailabilities of DEX-MR 20 mg and DEX-IR 10 mg b_i_d_ after intake of a normocaloric breakfast and a high-fat, high-calorie breakfast (multiple-dose study), 46 subjects_
| PK metric (unit) | Geometric Least Squares Mean | PE (%) | 90% CI | CVintra (%) | CVinter (%) | |
|---|---|---|---|---|---|---|
| Normocaloric breakfast (day 6) | ||||||
| DEX-MR 20 mg | DEX-IR 10 mg b.i.d. | |||||
| Cmax,ss (ng/mL) | 64.08 | 67.31 | 95.20 | 93.18 – 97.26 | 6.13 | 14.16 |
| Cτ,ss (h×ng/mL) | 17.45 | 17.19 | 101.49 | 97.92 – 105.18 | 10.23 | 22.05 |
| AUC0–τ,ss (h×ng/mL) | 904.3 | 897.9 | 100.71 | 98.99 – 102.45 | 4.91 | 16.19 |
| High-fat, high-calorie breakfast (day 7) | ||||||
| DEX-MR 20 mg | DEX-IR 10 mg b.i.d. | |||||
| Cmax,ss (ng/mL) | 59.60 | 68.00 | 87.64 | 85.50 – 89.85 | 7.09 | 13.73 |
| Cτ,ss (h×ng/mL) | 19.58 | 18.38 | 106.51 | 102.63– 110.53 | 10.62 | 21.36 |
| AUC0–τ,ss (h×ng/mL) | 895.4 | 903.5 | 99.11 | 97.35 – 100.90 | 5.12 | 15.55 |
Comparative bioavailabilities of DEX-MR 20 mg and DEX-IR 10 mg b_i_d_ after intake of a normocaloric vs_ a high-fat, high-calorie breakfast (breakfast study), 20 subjects_
| PK metric (unit) | Geometric Least Squares Mean | PE (%) | 90% CI | CVintra (%) | CVinter (%) | |
|---|---|---|---|---|---|---|
| Normocaloric breakfast | ||||||
| DEX-MR 20 mg | DEX-IR 10 mg b.i.d. | |||||
| Cmax (ng/mL) | 48.16 | 55.48 | 86.79 | 83.89 – 89.79 | 6.16 | 13.42 |
| AUC0–t (h×ng/mL) | 955.8 | 989.5 | 96.60 | 92.98 – 100.36 | 6.93 | 18.12 |
| AUC0–∞ (h×ng/mL) | 982.5 | 1012.9 | 97.00 | 93.24 – 100.91 | 7.16 | 18.97 |
| High-fat, high-calorie breakfast | ||||||
| DEX-MR 20 mg | DEX-IR 10 mg b.i.d. | |||||
| Cmax (ng/mL) | 45.82 | 53.98 | 84.88 | 80.07 – 89.99 | 10.31 | 13.37 |
| AUC0–t (h×ng/mL) | 908.3 | 914.7 | 99.31 | 95.47 – 103.31 | 6.93 | 17.09 |
| AUC0–∞ (h×ng/mL) | 932.4 | 942.5 | 98.93 | 95.31 – 102.68 | 6.54 | 17.08 |