TABLE 3.
Plasma apoC-II, apoC-III, and apoE kinetics in subjects treated with anacetrapib in combination with atorvastatin (panel A) or anacetrapib alone (panel B)
| Panel A (N = 29) | Panel B (N = 10) | All Subjects (N = 39) | ||||||||||
| Period 1 (ATV) | Period 2 (ANA+ATV) | Percent Change from Period 1 (95% CI) | P | Period 1 (PBO) | Period 2 (ANA) | Percent Change from Period 1 (95% CI) | P | Period 1 | Period 2 | Percent Change from Period 1 (95% CI) | P | |
| apoC-II PS (mg) | 193 (42.1) | 220 (40.2) | 13.9 (5.0, 23.5) | 0.002 | 203 (40.4) | 233 (43.7) | 14.8 (0.0, 31.8) | 0.050 | 198 (41.2) | 226 (40.6) | 14.4 (5.6, 23.9) | 0.002 |
| apoC-II FCR (pools/day) | 0.63 (25.4) | 0.57 (35.1) | −9.8 (−17.7, −1.2) | 0.028 | 0.56 (34.6) | 0.53 (32.5) | −5.6 (−19.3, 10.2) | 0.452 | 0.59 (28.0) | 0.55 (34.1) | −7.8 (−15.7, 0.9) | 0.077 |
| apoC-II PR (mg/kg/day) | 1.39 (32.5) | 1.43 (38.1) | 2.8 (−8.7, 15.7) | 0.641 | 1.45 (389.0) | 1.57 (28.0) | 8.6 (−11.2, 32.8) | 0.410 | 1.42 (33.7) | 1.50 (35.7) | 5.7 (−6.0, 18.7) | 0.345 |
| apoC-III PSa (mg) | 380 (34.0) | 498 (48.2) | 31.1 (6.5, 61.4) | 0.012 | 287 (34.9) | 504.7 (45.3) | 75.8 (23.3, 150.5) | 0.003 | 330 (36.3) | 502 (46.8) | 51.8 (23.6, 86.4) | <0.001 |
| apoC-III FCRa (pools/day) | 0.83 (0.3) | 0.75 (0.4) | −7.5 (−22.6, 7.1) | 0.465 | 0.86 (0.3) | 0.50 (0.4) | −35.0 (−69.9, −19.6) | 0.027 | 0.83 (0.3) | 0.70 (0.5) | −14.7 (−28.0, −1.0) | 0.078 |
| apoC-III PR (mg/kg/day) | 3.62 (1.7) | 4.15 (1.9) | 20.0 (−8.3, 51.6) | 0.108 | 3.07 (1.4) | 3.91 (3.0) | 27.5 (−42.3, 46.9) | 0.557 | 3.44 (1.9) | 4.15 (2.2) | 20.4 (−3.7, 42.9) | 0.065 |
| apoE PS (mg) | 154 (31.9) | 188 (39.5) | 22.0 (4.2, 42.9) | 0.015 | 145 (30.3) | 168 (31.7) | 15.2 (−11.9, 50.6) | 0.293 | 150 (31.2) | 178 (37.6) | 18.6 (1.5, 38.5) | 0.033 |
| apoE FCR (pools/day) | 3.71 (25.3) | 3.67 (46.6) | −1.0 (−18.4, 20.0) | 0.914 | 3.98 (20.1) | 3.57 (37.2) | −10.2 (−35.3, 24.7) | 0.510 | 3.84 (24.0) | 3.62 (43.8) | −5.7 (−22.1, 14.0) | 0.533 |
| apoE PR (mg/kg/day) | 6.55 (21.7) | 7.91 (28.2) | 20.8 (5.0, 38.8) | 0.009 | 7.34 (17.2) | 7.63 (32.8) | 3.9 (−18.1, 31.7) | 0.746 | 6.93 (21.1) | 7.77 (29.0) | 12.0 (−2.4, 28.5) | 0.103 |
Mixed model analysis performed on log scale. Geometric mean (% CV) displayed under period 1 and period 2. Percent change from period 1 and corresponding 95% CI calculated using 100 × (GMR − 1). ATV, atorvastatin; ANA, anacetrapib; PBO, placebo.
a
Nonparametric method used. Median (IQR) on raw scale displayed under period 1 and period 2. Hodges-Lehmann estimate (95% CI) back transformed from log scale displayed under percent change from period 1. P value from Wilcoxon signed rank test.