TABLE 4.
Summary of PK parameters of single dose study (SAD).
| Variable (unit) | SAD (adult) | SAD (elderly) | SAD (food effect) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose (mg) N (M/F) | 5a 6 (4/2) | 25b 6 (5/1) | 50c 6 (3/3) | 100a 6 (4/2) | 200b 6 (5/1) | 400c 6 (3/3) | 50 12 (7/5) | 150 12 (7/5) | Fasted, 100 6 (3/3) | Fed, 100 6 (3/3) | |
| C max (ng/ml) | Mean ± SD | 55.36 ± 22.65 | 266.489 ± 125.21 | 491.17 ± 172.51 | 1,602.98 ± 913.84 | 4,708.14 ± 2,960.82 | 7,153.41 ± 2052.63 | 557.06 ± 154.42 | 2,299.11 ± 868.25 | 1,619.58 ± 794.82 | 770.43 ± 129.05 |
| GM (95%CI) | 50.67 (31.62, 79.15) | 245.20 (135.10, 397.90) | 467.22 (310.10, 672.20) | 1,413.29 (644.10, 2,562.00) | 3,928.92 (1,601.00, 7,815.00) | 6,884.85 (4,999.00, 9,308.00) | 537.41 (458.90, 655.20) | 2,166.79 (1748.00, 2,851.00) | 1,483.00 (785.30, 2,454.00) | 761.20 (635.00, 905.90) | |
| AUC 0–24 (h·ng/ml) | Mean ± SD | 219.00 ± 58.50 | 1,434.47 ± 465.24 | 2,124.69 ± 485.22 | 4,590.58 ± 1,191.41 | 12,896.34 ± 5,806.48 | 25,108.27 ± 4,945.19 | 2,671.15 ± 654.60 | 8,405.46 ± 2,135.12 | 3,976.99 ± 394.03 | 3,929.60 ± 653.63 |
| GM (95%CI) | 212.58 (157.80, 280.60) | 1,379.28 (948.10, 1923.35) | 2078.61 (1,616.00, 2,634.00) | 4,470.21 (3,352.00, 5,839.00) | 11,932.98 (6,837.00, 19,011.00) | 24,684.91 (19,918.00, 30,298.00) | 2,597.77 (2,257.00, 3,087.00) | 8,167.36 (7,049.00, 9,762.00) | 4,064.00 (3,587.00, 4,590.00) | 3,789.00 (3,227.00, 4,431.00) | |
| AUC 0–48 (h·ng/ml) | Mean ± SD | 267.92 ± 83.15 | 1,673.31 ± 518.50 | 2,491.36 ± 661.03 | 5,281.86 ± 1,383.74 | 14,436.62 ± 6,422.69 | 27,814.48 ± 5,621.42 | 3,104.88 ± 707.61 | 9,576.71 ± 2,279.08 | 4,677.88 ± 580.03 | 4,526.18 ± 782.75 |
| GM (95%CI) | 257.46 (180.90, 355.10) | 1,613.98 (1,131.75, 2,217.08) | 2,419.32 (1798.00, 3,185.00) | 5,147.24 (3,841.00, 6,733.00) | 13,365.46 (7,732.00, 21,196.00) | 27,320.52 (21,915.00, 33,713.00) | 3,029.85 (2,657.00, 3,554.00) | 9,335.31 8,129.00, 11,025.00 | 4,656.00 (4,070.00, 5,307.00) | 4,501.00 (3,740.00, 5,384.00) | |
| AUC 0-∞ (h·ng/ml) | Mean ± SD | 300.66 ± 101.79 | 1834.28 ± 542.31 | 2,744.43 ± 847.92 | 5,756.48 ± 1,467.45 | 15,436.31 ± 6,666.12 | 29,305.01 ± 6,377.20 | 3,415.58 ± 678.57 | 10,218.60 ± 2,389.89 | 5,119.05 ± 766.96 | 5,141.52 ± 1,079.02 |
| GM (95%CI) | 287.20 (193.90, 407.40) | 1772.81 (1,267.68, 2,403.95) | 2,640.27 (1855.00, 3,634.00) | 5,622.68 (4,225.00, 7,298.00) | 14,338.23 (8,478.00, 22,450.00) | 28,695.55 (22,613.00, 35,998.00) | 3,351.98 (2,986.00, 3,846.00) | 9,964.42 (8,700.00, 11,737.00) | 5,077.00 (4,318.00, 5,942.00) | 5,040.00 (4,008.00, 6,274.00) | |
| K el (1/h) | Mean ± SD | 0.04 ± 0.01 | 0.04 ± 0.01 | 0.05 ± 0.01 | 0.05 ± 0.01 | 0.04 ± 0.01 | 0.05 ± 0.02 | 0.04 ± 0.01 | 0.05 ± 0.01 | 0.04 ± 0.01 | 0.04 ± 0.01 |
| GM (95%CI) | 0.04 (0.03,0.05) | 0.04 (0.03,0.05) | 0.05 (0.03,0.06) | 0.05 (0.03,0.06) | 0.04 (0.03,0.05) | 0.0482 (0.03,0.07) | 0.04 (0.03,0.05) | 0.0466 (0.03,0.04) | 0.04 (0.03,0.06) | 0.04 (0.03,0.05) | |
| T 1/2 (h) | Mean ± SD | 16.64 ± 3.13 | 18.67 ± 3.99 | 15.63 ± 4.27 | 16.08 ± 5.75 | 17.43 ± 4.20 | 14.85 ± 3.95 | 19.10 ± 8.02 | 15.19 ± 3.21 | 17.46 ± 4.40 | 18.71 ± 4.07 |
| GM (95%CI) | 16.40 (13.37, 19.92) | 18.31 (14.48, 22.86) | 15.16 (11.14, 20.11 | 15.40 (10.05, 22.11 | 17.01 (13.02, 21.83) | 14.37 (10.71, 19.00) | 17.84 (14.01, 24.19) | 14.88 (13.15, 17.23 | 16.91 (12.84, 22.08 | 18.36 (14.43, 22.98) | |
| Tmax (h) | Median (range) | 0.80 (0.33–3.00) | 1.01 (0.75–−3.00) | 1.12 (0.33–−4.00) | 1.37 (0.75–−3.00) | 1.40 (0.50–−4.00) | 1.75 (1.00–−3.00) | 1.12 (0.50–−3.00) | 0.87 (0.50–−2.00) | 0.94 (0.33–−2.02) | 2.01 (2.00–−3.00) |
N = Number of subjects with non-missing values.
a
Cohort 1 received 2 dose levels, 5 and 100 mg, separated by a washout period of 7 days.
b
Cohort 2 received 2 dose levels, 25 and 200 mg, separated by a washout period of 7 days.
c
Cohort 3 received 2 dose levels, 50 and 400 mg, separated by a washout period of 7 days.
Abbreviation: AUC, Area under curve; Kel, elimination rate constant; SAD, single ascending dose; SD, standard deviation; Tmax, time to reach Cmax.