Table 1 Changes in plasma lipid parameters in MAD cohorts of the phase 1 study of TLC-2716

TG (mg dl⁻¹)

Day 1

106.3 (35.6)

78.9 (30.8)

109.6 (49.0)

108.1 (37.7)

102.0 (45.5)

Change from day 1 to day 14

5.0 (−12.4, 22.4)

−14.3 (−34.9, 6.3)

−13.7 (−48.9, 21.5)

−35.8 (−46.8, −24.7)

−40.5 (−80.3, −0.7)

Placebo-adjusted percentage change from day 1 to day 14^a

—

−14.9 (−39.9, 6.2)

−3.7 (−34.3, 23.9)

−37.6 (−54.0, −19.9)

−38.5 (−67.9, −7.2)

P value versus placebo^b

—

0.281

0.681

0.003

0.024

RC, predose (mg dl⁻¹)

Day 1

19.2 (5.7)

15.0 (4.5)

19.9 (8.4)

19.6 (6.3)

18.3 (7.5)

Change from day 1 to day 14

1.3 (−1.6, 4.3)

−2.3 (−5.1, 0.5)

−2.3 (−8.6, 4.0)

−5.9 (−7.7, −4.0)

−5.5 (−12.4, 1.4)

Placebo-adjusted percentage change from day 1 to day 14^a

—

−16.8 (−38.6, 0)

−8.3 (−35.6, 22.6)

−33.5 (−50.3, −16.9)

−29.5 (−59.1, 2.6)

P value versus placebo^b

—

0.126

0.837

0.006

0.148

RC, 12 h postdose (mg dl⁻¹)

Day 1

24.8 (12.3)

16.8 (4.6)

25.9 (15.6)

19.9 (7.6)

18.9 (6.4)

Change from day 1 to day 14

9.1 (0.5, 17.7)

1.1 (−2.3, 4.6)

−2.8 (−16.4, 10.8)

−2.8 (−5.8, 0.1)

−4.1 (−8.3, −0.03)

Placebo-adjusted percentage change from day 1 to day 14^a

—

−33.2 (−77.3, 3.3)

−38.5 (−88.5, 14.4)

−59.2 (−90.2, −7.1)

−61.0 (−100, −11.7)

P value versus placebo^b

—

0.095

0.157

0.032

0.032

TC (mg dl⁻¹)

Day 1

188.5 (33.8)

172.8 (52.2)

191.6 (22.9)

187.5 (31.6)

172.5 (21.1)

Change from day 1 to day 14

−5.9 (−28.6, 16.8)

−8.1 (−31.4, 15.1)

−23.6 (−43.2, −4.0)

−11.1 (−23.7, 1.4)

−33.0 (−51.6, −14.4)

Placebo-adjusted percentage change from day 1 to day 14^a

—

2.8 (−19.5, 14.9)

−9.0 (−27.0, 6.8)

0.2 (−17.4, 12.0)

−11.1 (−35.3, 6.3)

P value versus placebo^b

—

0.975

0.702

0.975

0.048

LDL-C (mg dl⁻¹)

Day 1

114.9 (32.7)

101.4 (44.1)

120.5 (21.7)

112.9 (29.9)

99.0 (13.2)

Change from day 1 to day 14

−0.4 (−18.0, 17.1)

−2.9 (−21.9, 16.2)

−17.9 (−33.4, −2.3)

−3.7 (−14.9, 7.5)

−20.5 (−40.5, −0.5)

Placebo-adjusted percentage change from day 1 to day 14^a

—

3.6 (−23.1, 22.7)

−10.5 (−37.2, 6.8)

2.2 (−16.5, 19.0)

−17.3 (−40.1, 1.8)

P value versus placebo^b

—

0.781

0.598

0.781

0.352

Non-HDL-C (mg dl⁻¹)

Day 1

134.1 (34.0)

116.4 (45.6)

140.4 (24.1)

132.5 (31.6)

117.3 (10.6)

Change from day 1 to day 14

0.9 (−19.0, 20.8)

−5.1 (−23.6, 13.3)

−20.1 (−37.6, −2.7)

−9.6 (−20.9, 1.8)

−26.0 (−40.7, −11.3)

Placebo-adjusted percentage change from day 1 to day 14^a

—

1.3 (−29.4, 16.7)

−10.9 (−37.6, 6.6)

−2.2 (−23.0, 11.2)

−17.2 (−38.2, −8.3)

P value versus placebo^b

—

1.000

0.598

1

0.07

VLDL cholesterol (mg dl⁻¹)

Day 1

19.2 (5.7)

15.0 (4.5)

19.9 (8.4)

19.6 (6.3)

18.3 (7.5)

Change from day 1 to day 14

1.3 (−1.6, 4.3)

−2.3 (−5.1, 0.5)

−2.3 (−8.6, 4.0)

−5.9 (−7.7, −4.0)

−5.5 (−12.4, 1.4)

Placebo-adjusted percentage change from day 1 to day 14^a

—

−16.8 (−38.6, 0)

−8.3 (−35.6, 22.6)

−33.5 (−50.3, −16.9)

−29.5 (−59.1, 2.6)

P value versus placebo^b

—

0.126

0.837

0.0058

0.148

HDL-C (mg dl⁻¹)

Day 1

54.4 (14.3)

56.4 (14.8)

51.3 (10.6)

55.0 (14.3)

55.2 (15.6)

Change from day 1 to day 14

−6.8 (−11.7, −1.8)

−3.0 (−10.3, 4.3)

−3.4 (−7.3, 0.4)

−1.6 (−5.8, 2.7)

−7.0 (−12.6, −1.4)

Placebo-adjusted percentage change from day 1 to day 14^a

—

9.6 (−5.7, 19.0)

5.6 (−4.0, 14.2)

8.9 (−1.8, 16.3)

1.3 (−7.4, 7.7)

P value versus placebo^b

—

0.336

0.336

0.336

0.864

HDL particles (nmol l⁻¹)

Day 1

31.2 (3.9)

32.2 (4.4)

30.9 (4.2)

31.9 (5.3)

32.3 (5.7)

Change from day 1 to day 14

−2.4 (−5.1, 0.4)

−3.7 (−8.0, 0.6)

−3.2 (−6.4, −0.1)

−5.5 (−7.5, −3.4)

−7.5 (−11.5, −3.6)

Placebo-adjusted percentage change from day 1 to day 14^a

—

−4.0 (−19.0, 12.4)

−4.7 (−16.9, 11.0)

−8.6 (−19.0, 1.2)

−14.0 (−28.9, −1.6)

P value versus placebo^b

—

0.829

0.829

0.161

0.062

LDL particles (nmol l⁻¹)

Day 1

1,007.8 (304.8)

907.5 (333.4)

1,005.0 (198.6)

1,032.6 (317.3)

886.3 (145.9)

Change from day 1 to day 14

54.0 (−130.6, 238.6)

−173.8 (−337.0, −10.5)

−171.0 (−323.8, −18.2)

−201.1 (−314.2, −87.9)

−312.9 (−465.6, −160.2)

Placebo-adjusted percentage change from day 1 to day 14^a

—

−16.6 (−46.6, −0.6)

−16.1 (−45.2, 2.2)

−20.3 (−45.9, −3.4)

−36.5 (−67.8, −19.8)

P value versus placebo^b

—

0.058

0.122

0.023

0.008

Small LDL particles (nmol l⁻¹)

Day 1

479.7 (209.3)

357.9 (171.2)

542.1 (190.4)

526.3 (268.3)

431.6 (210.6)

Change from day 1 to day 14

34.0 (−148.4, 216.4)

−81.1 (−153.5, −8.7)

−105.5 (−240.7, 29.7)

−159.5 (−265.5, −53.4)

−187.1 (−391.9, 17.6)

Placebo-adjusted percentage change from day 1 to day 14^a

—

−39.7 (−82.7, 21.8)

−34.5 (−80.6 21.5)

−52.2 (−100.1, 9.8)

−60.8 (−121.4, 0.1)

P value versus placebo^b

—

0.230

0.360

0.205

0.205

ApoB (mg dl⁻¹)

Day 1

94.3 (18.6)

84.8 (27.7)

96.4 (14.9)

93.2 (19.7)

79.7 (10.1)

Change from day 1 to day 14

0.3 (−11.8, 12.5)

−3.1 (−18.5, 12.3)

−9.9 (−25.1, 5.4)

0.4 (−7.3, 8.0)

−10.5 (−27.6, 6.6)

Placebo-adjusted percentage change from day 1 to day 14^a

—

1.3 (−19.2, 19.1)

−14.2 (−23.2, 11.7)

1.0 (−12.5, 19.1)

−10.2 (−34.2, 4.1)

P value versus placebo^b

—

0.975

0.816

0.975

0.816

LPIR

Day 1

53.2 (15.9)

37.9 (15.4)

51.3 (22.1)

51.8 (18.4)

44.9 (16.4)

Change from day 1 to day 14

1.2 (−6.7, 9.1)

−0.5 (−7.7, 6.7)

−3.8 (−13.7, 6.2)

−13.1 (−19.4, −6.7)

−10.5 (−15.1, −5.9)

Placebo-adjusted percentage change from day 1 to day 14^a

—

1.0 (−30.4, 28.0)

−7.7 (−28.6, 30.3)

−23.8 (−49.1, −7.1)

−26.2 (−54.1, −4.2)

P value versus placebo^b

—

0.897

0.897

0.05

0.05

TG/HDL-C

Day 1

2.2 (1.2)

1.6 (1.0)

2.4 (1.5)

2.2 (1.2)

2.1 (1.4)

Change from day 1 to day 14

0.4 (−0.04, 0.8)

−0.3 (−0.9, 0.3)

−0.3 (−1.1, 0.5)

−0.6 (−0.9, −0.3)

−0.7 (−1.6, 0.2)

Placebo-adjusted percentage change from day 1 to day 14^a

—

−17.6 (−57.0, 6.3)

−11.0 (−48.7, 20.5)

−43.5 (−68.6, −19.2)

−44.5 (−75.4, −1.6)

P value versus placebo^b

—

0.12

0.536

0.0018

0.099