Table 3. ApoB kinetics.
The effects of mipomersen on apoB metabolism were determined from 17 kinetic studies at the end of the placebo and mipomersen treatment periods. Absolute values for the placebo and mipomersen periods are shown. If the data were found to be normally distributed by the Kolmogorov-Smirnov test, they are presented as means (±SD), and statistical analyses were performed on percent change for each endpoint on mipomersen from placebo using paired t tests. If the data were not normally distributed, the median and interquartile values (in parentheses) are shown for percent change, and the Wilcoxon rank-sum test was performed to test for significance.
| Parameter | Placebo | Mipomersen | Change (%) | P value |
|---|---|---|---|---|
| VLDL apoB FCR (pools/day) | 7.6 (3.6) | 9.9 (4.6) | 23.0 (−7.4, 55.6) | 0.023 |
| VLDL apoB PR (mg kg−1 day−1) | 21.7 (11.3) | 19.0 (10.9) | −17.6 (−32.7, −0.9) | 0.15 |
| VLDL to IDL (% conversion)* | 70.2 (24.2) | 58.2 (24.5) | −12.1 | 0.09 |
| IDL apoB FCR (pools/day) | 5.5 (3.5) | 5.8 (3.6) | 11.1 | 0.30 |
| IDL apoB PR (mg kg−1 day−1) | 15.0 (8.1) | 10.2 (6.9) | −32.7 (−53.5, −5.7) | 0.05 |
| IDL to LDL (% conversion)* | 76.2 (23) | 74.4 (26) | −1.7 | 0.84 |
| LDL apoB FCR (pools/day) | 0.52 (0.14) | 0.65 (0.19) | 29.7 | <0.001 |
| LDL apoB PR (mg kg−1 day−1) | 12.7 (4.6) | 8.8 (3.1) | −26.5 | 0.001 |
| Direct LDL PR (mg kg−1 day−1)† | 2.6 (3.5) | 2.2 (1.5) | 0.0 (−0.8, 1.5) | 0.89 |
| LDL apoB PR from direct LDL secretion (%)* | 21.3 (22) | 26.8 (18) | 5.5 | 0.38 |
| Total apoB PR (sum VLDL PR and direct LDL PR) (mg kg−1 day−1) | 24.3 (11.5) | 21.3 (10.7) | −15.1 (−34.5, −7.4) | 0.26 |
| VLDL TG FCR (pools/hour) | 10.5 (7.9) | 13.2 (8.4) | 46.3 | 0.03 |
| VLDL TG PR (mg kg−1 hour−1) | 13.1 (6.4) | 13.3 (7.0) | 10.0 | 0.40 |
| VLDL TG PR/VLDL apoB PR ratio | 22.9 (27.0) | 26.2 (37.0) | 16.5 (−7.8, 93.2) | 0.05 |
| Plasma VLDL TG/VLDL apoB ratio | 14.5 (13.7) | 15.3 (9.0) | 24.6 | 0.03 |
For the percent conversions (VLDL to IDL; IDL to LDL), absolute differences between placebo and mipomersen results were used to test for significance.
Some direct LDL secretion rates were zero, so no percent change was calculated for this parameter; instead, values are absolute differences.