Table 2.
Changes in pharmacodynamic parameters at trough level (predose) on day 14
| Dose | n | Mean % change from baseline (90% CI) | Mean % change vs placebo (90 % CI) |
|---|---|---|---|
| CETP activity | |||
| Placebo | 19 | 1.48 (−7.39, 10.35) | |
| 10 mg | 12 | −14.60 (−22.33, −6.87) | −16.08 (−23.23, −8.94)*** |
| 100 mg | 12 | −64.54 (−73.08, −56.00) | −66.02 (−78.93, −53.11)*** |
| 300 mg | 10 | −84.26 (−91.34, −77.18) | −85.74 (−97.43, −74.05)*** |
| 600 mg | 19 | −91.18 (−99.71, −82.66) | −92.66 (−104.92, −80.41)*** |
| CETP mass | |||
| Placebo | 19 | −0.40 (−12.63, 11.84) | |
| 10 mg | 12 | 20.18 (9.92, 30.45) | 20.58 (11.28, 29.88)*** |
| 100 mg | 12 | 95.77 (82.14, 109.41) | 96.17 (76.37, 115.97)*** |
| 300 mg | 10 | 131.72 (122.10, 141.34) | 132.12 (115.85, 148.38)*** |
| 600 mg | 19 | 145.34 (133.29, 157.39) | 145.73 (128.99, 162.48)*** |
| Total cholesterol | |||
| Placebo | 26 | −0.65 (−8.14, 6.83) | |
| 10 mg | 12 | −4.92 (−15.93, 6.10) | −4.26 (−17.58, 9.06) |
| 100 mg | 12 | 6.83 (−4.18, 17.85) | 7.49 (−5.83, 20.81) |
| 300 mg | 10 | 15.60 (3.53, 27.67) | 16.25 (2.05, 30.46) |
| 600 mg | 25 | 15.48 (7.85, 23.11) | 16.13 (5.44, 26.82)* |
| HDL-C | |||
| Placebo | 19 | −6.33 (−14.31, 1.64) | |
| 10 mg | 12 | 11.69 (4.39, 18.99) | 18.02 (9.76, 26.28)*** |
| 100 mg | 12 | 59.28 (51.54, 67.02) | 65.61 (53.34, 77.88)*** |
| 300 mg | 10 | 75.22 (68.87, 81.58) | 81.56 (70.90, 92.22)*** |
| 600 mg | 19 | 80.50 (73.05, 87.95) | 86.83 (75.96, 97.71)*** |
| LDL-C | |||
| Placebo | 19 | 1.65 (−3.43, 6.73) | |
| 10 mg | 12 | −11.94 (−18.31, −5.57) | −13.59 (−21.83, −5.35)** |
| 100 mg | 12 | −24.47 (−27.68, −21.26) | −26.13 (−32.39, −19.86)*** |
| 300 mg | 10 | −26.39 (−29.92, −22.85) | −28.04 (−34.18, −21.90)*** |
| 600 mg | 19 | −26.91 (−30.71, −23.11) | −28.56 (−34.76, −22.37)*** |
| Triglycerides | |||
| Placebo | 26 | −18.42 (−27.92, −8.93) | |
| 10 mg | 12 | −12.92 (−26.89, 1.06) | 5.51 (−11.39, 22.40) |
| 100 mg | 12 | −3.75 (−17.73, 10.23) | 14.67 (−2.22, 31.57) |
| 300 mg | 10 | −2.10 (−17.41, 13.21) | 16.32 (−1.69, 34.34) |
| 600 mg | 25 | −22.08 (−31.76, −12.40) | −3.66 (−17.22, 9.91) |
| Apo AI | |||
| Placebo | 12 | −11.76 (−18.51, −5.01) | |
| 10 mg | 12 | 3.53 (−2.23, 9.30) | 15.29 (7.74, 22.84)** |
| 100 mg | 12 | 24.61 (20.07, 29.15) | 36.37 (27.66, 45.08)*** |
| 300 mg | 10 | 28.75 (23.70, 33.80) | 40.50 (31.66, 49.34)*** |
| 600 mg | 11 | 29.93 (24.51, 35.35) | 41.69 (32.70, 50.67)*** |
| Apo AII | |||
| Placebo | 12 | −5.59 (−10.57, −0.61) | |
| 10 mg | 12 | −1.30 (−5.34, 2.73) | 4.29 (−0.90, 9.48) |
| 100 mg | 12 | 8.85 (4.69, 13.02) | 14.44 (7.16, 21.72)** |
| 300 mg | 10 | 11.93 (7.75, 16.10) | 17.52 (10.86, 24.17)*** |
| 600 mg | 11 | 12.91 (8.06, 17.77) | 18.50 (11.71, 25.29)*** |
| Apo B | |||
| Placebo | 12 | 6.96 (1.27, 12.66) | |
| 10 mg | 12 | −8.09 (−13.41, −2.77) | −15.05 (−22.68, −7.43)** |
| 100 mg | 12 | −17.64 (−20.84, −14.43) | −24.60 (−31.28, −17.92)*** |
| 300 mg | 10 | −18.85 (−22.45, −15.25) | −25.81 (−32.59, −19.04)*** |
| 600 mg | 11 | −19.17 (−22.94, −15.41) | −26.14 (−32.97, −19.30)*** |
| Ratio of apo B/apo AI | |||
| Placebo | 12 | 19.76 (13.28, 26.24) | |
| 10 mg | 12 | −6.87 (−12.72, −1.02) | −26.63 (−34.88, −18.38)*** |
| 100 mg | 12 | −31.84 (−35.59, −28.09) | −51.60 (−59.36, −43.83)*** |
| 300 mg | 10 | −35.69 (−39.92, −31.46) | −55.45 (−63.26, −47.63)*** |
| 600 mg | 11 | −36.74 (−41.23, −32.25) | −56.50 (−64.39, −48.61)*** |
| Apo E | |||
| Placebo | 12 | 11.35 (−7.54, 30.24) | |
| 10 mg | 12 | 19.70 (5.10, 34.30) | 8.36 (−2.89, 19.60) |
| 100 mg | 12 | 55.81 (36.13, 75.50) | 44.47 (14.63, 74.30)* |
| 300 mg | 10 | 76.75 (62.23, 91.28) | 65.40 (40.39, 90.42)*** |
| 600 mg | 11 | 85.48 (65.47, 105.49) | 74.13 (47.95, 100.31)*** |
Apo, Apolipoprotein; CI, confidence interval; CETP, cholesteryl ester transfer protein. *P < 0.05; **P < 0.01; ***P < 0.001. n = number of subjects per dose group.