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Variability of total Css,trough was predominantly explained by the range of AAG concentrations.
No differences by race/ethnicity were seen for total RSDI, total CSS, or any mean subscale score (Table 4).
Of note, the extreme AAG concentrations (5th and 95th percentiles) corresponded to as high as −47 and 101% variation for total Css,trough.
Age, body weight, and population were shown to have no clinically significant impact based on the sensitivity analysis (<5% variation on total Css,trough and <17% on unbound).
The population predicted 5th and 95th percentile of total Css,trough for the actual patients with QD dosing of the 150 mg phase II formulation were 7.6 and 53 μM, respectively, corresponding to −66.7 and 132.5% variation around the total Css,trough predicted for the typical patient (22.8 μM).
All secondary outcome measures consistently supported the primary finding, showing improvement in the total CSS score, its subscores for objective signs and subjective symptoms, and in most of the individual signs and symptoms.
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The unweighted sum of all 11 items makes up the individual's total CSS-SHR score (0-54 points).
The unweighted sum of all 11 items makes up the individual's total CSS-SHR score, ranging from 0 to 54.
We found that 174 (3.86% of the total) intergenic CSSs overlap with binding sites for SUZ12 and 9 (0.20% of the total) overlap binding sites for C-MYC.
Median time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages].
A responder was defined by a ≥ 50% improvement in the CSS total score between Day 10 visit and baseline.
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