Figure 1 Study schematic with the disposition of participants in the single-dose part of the study.
Figure 1 Study schematic with the disposition of participants in the single-dose part of the study.
Figure 2 Mean (SEM) plasma valproic acid concentrations during daily dosing with CS1, FII 276 mg daily (Days 1‒14) and 552 mg daily (Days 15‒28).
Figure 3 Mean (SEM) plasma valproic acid concentrations following the final dose on Day 28.
Figure 4 Mean (SEM) plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) during treatment with CS1, FII, 276 mg daily (Days 1‒14) and 552 mg daily (Days 15‒28) i n the multiple ascending dosing part of the study.
Figure 5 Association between clot lysis time and mean (SEM) plasma PAI-1 concentrations over 24 hours.
Figure 6 Overall correlation (n=125) between clot lysis time and plasma PAI-1 concentrations.
|
|
Single-dose (n=17) Three formulations of CS1 |
|
Repeated dosing (n=13) |
|
|
FI (n=7) |
FII (n=6) |
FIII (n=4) |
Total |
|
Age (years) |
50.6 (6.9) |
52.2 (8.2) |
57.3 (7.0) |
52.7 (7.4) |
52.2 (6.6) |
Gender (female/male) |
4/3 (57%/43%) |
3/3 (50%/50%) |
1/3 (25%/75%) |
8/9 (47%/53%) |
5/8 (38%/62%) |
Race (White/Hispanic or Latino) |
6/1 (86%/14%) |
5/1 (83%/17%) |
3/1 (75%/25%) |
14/3 (82%/18%) |
13 (100%) |
Body mass index (kg/m2) |
29.7 (2.2) |
33.3 (1.2) |
30.8 (2.8) |
31.2 (2.5) |
30.9 (2.7) |
Height (cm) |
170 (12.7) |
168 (10.8) |
172 (8.8) |
170 (10.7) |
168 (12.5) |
Weight (kg) |
86 (12.1) |
94.2 (14.4) |
90.3 (10.4) |
89.9 (12.4) |
87.2 (12) |
Table 1. Demographic characteristics of participants. Results are presented as mean (SD) or as number (%).
|
Baseline |
Day 15 Measured 14 hours after last dose |
Day 29 Measured 14 hours after last dose |
PAI-1(µg/L) |
52.3 (28.6) |
62.2 (37.5) |
41.2 (22.5)* |
PAP(µg/L) |
434.2 (555.4) |
391.3 (483.0) |
353.1 (392.5) |
Fibrinogen (g/L) |
3.82 (0.56) |
3.49 (0.48) |
3.33 (0.58) |
hs-CRP (mg/L) |
4.27 (5.21) |
2.94 (3.06) |
4.44 (3.98) |
Platelets unit (109/L) |
161.7 (55.4) |
148.4 (32.4) |
155.7 (40.0) |
D-dimer (mg/L) |
0.35 (0.08) |
0.37 (0.08) |
0.61 (0.45) |
Bleeding time (minutes) |
4.96 (1.14) |
5.00 (1.60) |
4.67 (1.15) |
Table 2. Changes in pharmacodynamic parameters from baseline (Day 1) to Days 15 (end of 276 mg dosing) and 29 (end of 552 mg dosing) of multiple dosing with CS1, FII. Results are presented as mean (SD).
hs-CRP: high-sensitivity C-reactive peptide; PAP: plasmin- 2-antiplasmin complex; PAI-1: plasminogen activator inhibitor
*P=0.0425 versus Day 15, Wilcoxon signed rank test