Thirty two healthy male subjects (Sub) entered a double-blind, placebo-controlled, single rising dose study of Drug P. There were four panels of eight subjects. In each panel, subjects were randomized to one of four sequences of increasing doses of Drug P and placebo. For example, in Panel 1 two subjects received placebo, 10mg, 20mg, 40mg; two subjects received 10mg, placebo, 20mg, 40mg; two subjects received 10 mg, 20mg, placebo, 40mg, and two subjects received 10mg, 20mg, 40mg, and placebo. A one week washout period separated the treatments. Panel 2 (40mg, 80mg, 120mg, placebo), Panel 3 (120mg, 150mg, 200mg, placebo), and Panel 4 (200mg, 250mg, 300mg, placebo) followed Panel 1 in order.
Plasma samples were taken from each subject for each treatment at specified time points both pre and post dose, from which area-under-the-plasma-concentration-vs.-time curve, AUC (ng·hr/mL), and maximum plasma concentration, Cmax (ng/mL), were calculated for both the parent (P) compound, Drug P, and its metabolite (M).
Part 6 - Table 4 | ||||||||||||||
Single Rising Dose Pharmacokinetic Study | ||||||||||||||
|
|
|
|
AUC |
Cmax |
|||||||||
Panel |
Sub |
Cpd |
10mg |
20mg |
40mg |
10mg |
20mg |
40mg |
||||||
|
|
|
|
|
|
|||||||||
1 |
1 |
P |
91.5 |
217.8 |
330.7 |
42.4 |
82.0 |
241.3 |
||||||
|
|
M |
395.6 |
728.3 |
2170.2 |
39.6 |
70.0 |
310.5 |
||||||
|
2 |
P |
96.6 |
82.1 |
705.0 |
29.2 |
68.9 |
202.8 |
||||||
|
|
M |
714.1 |
630.7 |
1728.5 |
25.4 |
47.1 |
197.0 |
||||||
|
3 |
P |
NA |
146.4 |
266.9 |
30.2 |
124.3 |
117.0 |
||||||
|
|
M |
334.2 |
856.4 |
1650.7 |
45.3 |
113.7 |
248.1 |
||||||
|
4 |
P |
NA |
84.4 |
140.4 |
NA |
105.8 |
103.2 |
||||||
|
|
M |
370.8 |
707.7 |
982.3 |
30.0 |
70.9 |
117.8 |
||||||
|
5 |
P |
NA |
NA |
NA |
NA |
NA |
NA |
||||||
|
|
M |
NA |
NA |
NA |
NA |
NA |
NA |
||||||
|
6 |
P |
NA |
116.7 |
229.8 |
NA |
25.2 |
74.4 |
||||||
|
|
M |
NA |
NA |
NA |
NA |
NA |
NA |
||||||
|
7 |
P |
NA |
215.1 |
426.2 |
25.5 |
52.1 |
139.9 |
||||||
|
|
M |
571.1 |
978.0 |
1863.6 |
45.2 |
85.1 |
247.9 |
||||||
|
8 |
P |
NA |
102.2 |
312.8 |
20.2 |
43.0 |
127.6 |
||||||
|
|
M |
220.0 |
766.4 |
1664.0 |
26.6 |
78.0 |
266.2 |
||||||
|
|
|
|
|
|
|
|
|
||||||
40mg |
80mg |
120mg |
40mg |
80mg |
120mg |
|||||||||
2 |
9 |
P |
378.2 |
901.7 |
1329.9 |
171.7 |
809.3 |
682.4 |
||||||
|
|
M |
2211.9 |
5144.7 |
8151.4 |
204.4 |
702.8 |
1222.8 |
||||||
|
10 |
P |
362.8 |
923.7 |
NA |
239.5 |
498.4 |
NA |
||||||
|
|
M |
1354.8 |
2865.2 |
NA |
128.8 |
327.3 |
NA |
||||||
|
11 |
P |
353.9 |
778.4 |
996.0 |
197.0 |
372.2 |
710.3 |
||||||
|
|
M |
1897.7 |
3336.0 |
4594.0 |
210.5 |
516.9 |
945.8 |
||||||
|
12 |
P |
255.1 |
649.6 |
1123.4 |
326.0 |
477.0 |
947.0 |
||||||
|
|
M |
1797.0 |
4183.2 |
6340.9 |
178.3 |
586.5 |
1032.8 |
||||||
|
13 |
P |
526.1 |
927.6 |
1566.1 |
379.9 |
454.1 |
1288.7 |
||||||
|
|
M |
940.5 |
1883.3 |
2857.9 |
110.0 |
228.1 |
493.7 |
||||||
|
14 |
P |
1036.7 |
2115.5 |
2948.1 |
541.2 |
922.3 |
1758.7 |
||||||
|
|
M |
2828.3 |
6153.9 |
8323.7 |
269.7 |
715.3 |
1094.2 |
||||||
|
15 |
P |
359.5 |
845.3 |
1203.0 |
234.5 |
539.5 |
759.7 |
||||||
|
|
M |
1855.1 |
3318.4 |
4512.2 |
199.2 |
445.8 |
875.2 |
||||||
|
16 |
P |
188.2 |
319.9 |
537.6 |
125.4 |
226.8 |
392.8 |
||||||
|
|
M |
1146.8 |
2229.3 |
3307.6 |
112.4 |
322.0 |
652.1 |
||||||
120mg |
150mg |
200mg |
120mg |
150mg |
200mg |
|||||||||
|
|
|
|
|
|
|
|
|
||||||
3 |
17 |
P |
1323.2 |
2076.8 |
2917.6 |
828.4 |
1195.8 |
2213.6 |
||||||
|
|
M |
5486.3 |
9339.0 |
10953.6 |
695.2 |
1263.2 |
1730.0 |
||||||
|
18 |
P |
1648.4 |
1726.3 |
2344.0 |
1098.3 |
1139.9 |
2049.8 |
||||||
|
|
M |
6349.5 |
7908.5 |
9703.9 |
1074.1 |
1376.3 |
1890.9 |
||||||
|
19 |
P |
1709.6 |
1829.0 |
3245.5 |
1299.2 |
1117.5 |
2447.4 |
||||||
|
|
M |
5515.3 |
5776.8 |
7694.9 |
921.6 |
895.9 |
1224.1 |
||||||
|
20 |
P |
649.8 |
1343.8 |
2040.0 |
401.6 |
1053.8 |
2124.9 |
||||||
|
|
M |
4645.0 |
6782.7 |
7080.4 |
934.2 |
1338.2 |
1863.0 |
||||||
|
21 |
P |
871.0 |
1674.7 |
2370.3 |
562.8 |
1681.7 |
2526.9 |
||||||
|
|
M |
3450.0 |
4684.1 |
5842.8 |
771.3 |
1113.4 |
1309.9 |
||||||
|
22 |
P |
1289.0 |
1562.6 |
2462.8 |
900.7 |
661.6 |
1925.6 |
||||||
|
|
M |
6803.3 |
8677.2 |
11885.2 |
967.9 |
1412.8 |
2406.2 |
||||||
|
23 |
P |
948.2 |
1220.9 |
2091.1 |
548.0 |
694.4 |
2760.9 |
||||||
|
|
M |
3926.1 |
4727.5 |
6029.7 |
740.1 |
953.3 |
1674.9 |
||||||
|
24 |
P |
1022.1 |
1990.2 |
2730.7 |
819.2 |
1583.7 |
1217.0 |
||||||
|
|
M |
5742.9 |
6559.2 |
8146.4 |
1194.8 |
1579.6 |
1601.4 |
||||||
|
|
|
|
|
|
|
|
|
||||||
|
|
|
200mg |
250mg |
300mg |
200mg |
250mg |
300mg |
||||||
|
|
|
|
|
|
|
|
|||||||
4 |
25 |
P |
2358.6 |
2688.1 |
3459.6 |
1627.8 |
1711.7 |
2407.8 |
||||||
|
|
M |
11114.6 |
12873.2 |
15159.7 |
2856.0 |
3062.9 |
2941.7 |
||||||
|
26 |
P |
1913.3 |
1990.2 |
1961.0 |
2034.6 |
945.4 |
892.2 |
||||||
|
|
M |
6910.2 |
6270.3 |
6688.4 |
1233.4 |
1242.4 |
1281.2 |
||||||
|
27 |
P |
3753.1 |
3934.5 |
4449.5 |
4398.4 |
4625.8 |
4648.2 |
||||||
|
|
M |
9932.1 |
12219.3 |
11192.6 |
1693.8 |
2213.8 |
2413.2 |
||||||
|
28 |
P |
3066.3 |
3966.3 |
6527.5 |
2717.2 |
3366.3 |
5420.5 |
||||||
|
|
M |
7512.8 |
9354.6 |
13069.9 |
1984.9 |
2400.4 |
3012.7 |
||||||
|
29 |
P |
1803.3 |
2469.5 |
3268.2 |
2364.6 |
2360.4 |
3240.6 |
||||||
|
|
M |
7657.6 |
10173.0 |
12212.7 |
1622.3 |
2304.4 |
2895.6 |
||||||
|
30 |
P |
NA |
NA |
NA |
NA |
NA |
NA |
||||||
|
|
M |
NA |
NA |
NA |
NA |
NA |
NA |
||||||
|
31 |
P |
1412.2 |
1724.5 |
2769.7 |
1468.5 |
1161.0 |
1902.6 |
||||||
|
|
M |
5219.3 |
5391.6 |
7108.8 |
1232.2 |
1442.3 |
1920.9 |
||||||
|
32 |
P |
1065.2 |
1198.2 |
2011.2 |
782.7 |
660.5 |
1580.4 |
||||||
|
|
M |
6094.8 |
7122.5 |
8394.4 |
1454.6 |
1613.1 |
1824.7 |
||||||
Bradstreet, T. E. and Short, T. H. (2006) "Favorite Data Sets from Early Phases of Drug Research - Part 6." Proceedings of the Section on Statistical Education of the American Statistical Association.