GC28210

F. Hoffmann-La Roche AG

Grenzacherstrasse 124, CH-4070, Basel, Switzerland,

Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com

Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com

No

No

No

Final

19 Sep 2013

No

Yes

22 Jul 2013

No

To evaluate the safety and efficacy of MPSK3169A on top of standard-of-care (SOC) statin in participants with a low-density lipoprotein cholesterol (LDLc) of 90−250 milligrams per deciliter (mg/dL) and either coronary heart disease (CHD) or a CHD risk equivalent.

Efforts to minimize risk included the following: judicious eligibility of participants who may benefit from LDLc lowering because of a combination of high cardiovascular risk and LDLc levels well above the goal of 70 mg/dL, use of SOC statin therapy for all participants, regular safety evaluations overseen by the investigator, study overseen by an internal monitoring committee (IMC), and the use of a minimum threshold of LDLc below which MPSK3169A would be withheld. This study was conducted in full conformance with the International Conference on Harmonisation (ICH) E6 guideline for Good Clinical Practice (GCP) and the principles of the Declaration of Helsinki or the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual.

21 May 2012

No

Yes

Norway: 21

Slovakia: 10

Czech Republic: 9

Germany: 1

Hungary: 13

Canada: 44

New Zealand: 9

South Africa: 4

United States: 137

248

54

0

0

0

0

0

0

125

123

0

Treatment Period (overall period)

Randomised - controlled

Yes

MPSK3169A

RO6801831

Solution for injection

Subcutaneous use

All participants in the study received subcutaneous doses of MPSK3169A or matching placebo every four weeks.

MPSK3169A

RO6801831

Solution for injection

Subcutaneous use

All participants in the study received subcutaneous doses of MPSK3169A or matching placebo every four weeks.

MPSK3169A

RO6801831

Solution for injection

Subcutaneous use

All participants in the study received subcutaneous doses of MPSK3169A or matching placebo every four weeks.

MPSK3169A

Solution for injection

Subcutaneous use

All participants in the study received subcutaneous doses of MPSK3169A or matching placebo every four weeks.

MPSK3169A

RO6801831

Solution for injection

Subcutaneous use

All participants in the study received subcutaneous doses of MPSK3169A or matching placebo every four weeks.

Placebo

Placebo

Solution for injection

Subcutaneous use

All participants in the study received subcutaneous doses of matching placebo every four weeks.

MPSK3169A 400 mg once every 4 weeks (Q4W)

MPSK3169A 200 mg Q8W

MPSK3169A 400 mg Q8W

MPSK3169A 800 mg Q8W

MPSK3169A 800 mg Q12W

Placebo

MPSK3169A 400 mg once every 4 weeks (Q4W)

MPSK3169A 200 mg Q8W

MPSK3169A 400 mg Q8W

MPSK3169A 800 mg Q8W

MPSK3169A 800 mg Q12W

Placebo

Modified Intent to Treat (mITT) population included participants who were randomized and received at least 1 dose of study drug. Participants with baseline measurement and post baseline measurement of LDLc concentration at Day 169 were included in the analysis of this end point.

Primary

Baseline, Day 169

This analysis was performed on Day 169. Least squares (LS) mean difference, 95% confidence intervals (CIs) and p−values were based on an analysis of covariance model adjusted for baseline LDLc (less than [<] 120 mg/dL, greater than or equal to [≥] 120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=104.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

104

Pre-specified

61.8

2-sided

Standard error of the mean

5.1

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=80.

Placebo v MPSK3169A 200 mg Q8W

80

Pre-specified

1.8

2-sided

Standard error of the mean

6.5

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=87.

Placebo v MPSK3169A 400 mg Q8W

87

Pre-specified

21

2-sided

Standard error of the mean

5.9

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=103.

Placebo v MPSK3169A 800 mg Q8W

103

Pre-specified

43.5

2-sided

Standard error of the mean

5.2

Differences from Pbo are the difference between LS means with the standard error. P−values are adjusted for baseline LDLc (<120 mg/dL, >=120 mg/dL) and diabetes status (yes,no) and not adjusted for multiple testing. Number of subjects included in analysis=78.

Placebo v MPSK3169A 800 mg Q12W

78

Pre-specified

12.9

2-sided

Standard error of the mean

6.8

Nadir is defined as the planned visit, up to day 169, with the greatest mean decrease within a treatment group. mITT population participants with baseline measurement and at least 1 postbaseline measurement of LDLc concentration were included in the analysis of this end point.

Secondary

Baseline, up to Day 169 (Nadir)

This analysis was performed at nadir timepoint. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=111.

Placebo v MPSK3169A 400 mg once every 4 weeks (Q4W)

111

Pre-specified

72.6

2-sided

Standard error of the mean

4.4

This analysis was performed at nadir timepoint. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=81.

Placebo v MPSK3169A 200 mg Q8W

81

Pre-specified

55.9

2-sided

Standard error of the mean

5.8

This analysis was performed at nadir timepoint. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=88.

Placebo v MPSK3169A 400 mg Q8W

88

Pre-specified

67.5

2-sided

Standard error of the mean

5.3

This analysis was performed at nadir timepoint. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=107.

Placebo v MPSK3169A 800 mg Q8W

107

Pre-specified

70.6

2-sided

Standard error of the mean

4.5

This analysis was performed at nadir timepoint. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=83.

Placebo v MPSK3169A 800 mg Q12W

83

Pre-specified

73.9

2-sided

Standard error of the mean

5.6

This outcome was calculated by dividing the average change from baseline of LDLc concentration by average number of weeks of study treatment. mITTpopulation participants with baseline and post baseline measurement of LDLc concentration at Day 169 were included in the analysis of this end point.

Secondary

Baseline, Day 169

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=103.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

103

Pre-specified

68.5

2-sided

Standard error of the mean

3.8

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=80.

Placebo v MPSK3169A 200 mg Q8W

80

Pre-specified

25.5

2-sided

Standard error of the mean

4.8

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=87.

Placebo v MPSK3169A 400 mg Q8W

87

Pre-specified

48.8

2-sided

Standard error of the mean

4.4

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=102.

Placebo v MPSK3169A 800 mg Q8W

102

Pre-specified

62.2

2-sided

Standard error of the mean

3.8

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=78.

Placebo v MPSK3169A 800 mg Q12W

78

Pre-specified

51.7

2-sided

Standard error of the mean

5

mITT population participants with baseline and post baseline measurement of LDLc concentration at Day 169 were included in the analysis of this end point.

Secondary

Baseline, Day 169

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=103.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

103

Pre-specified

56.5

2-sided

Standard error of the mean

2.8

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=80.

Placebo v MPSK3169A 200 mg Q8W

80

Pre-specified

22

2-sided

Standard error of the mean

3.5

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=87.

Placebo v MPSK3169A 400 mg Q8W

87

Pre-specified

38.5

2-sided

Standard error of the mean

3.2

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=102.

Placebo v MPSK3169A 800 mg Q8W

102

Pre-specified

52.1

2-sided

Standard error of the mean

2.8

This analysis was performed on Day 169. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=78.

Placebo v MPSK3169A 800 mg Q12W

78

Pre-specified

41.6

2-sided

Standard error of the mean

3.6

Nadir is defined as the planned visit, up to day 169, with the greatest mean decrease within a treatment group. mITT population participants with baseline and post baseline measurement of LDLc concentration at Day 169 were included in the analysis of this end point. "n" value indicates the number of participants evaluable at a specified timepoint for a particular treatment arm.

Secondary

Baseline, Day 169, up to Day 169 (Nadir)

This analysis was performed on Day 169. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=104.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

111

Pre-specified

51

2-sided

Standard error of the mean

3.8

This analysis was performed on Day 169. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=80.

Placebo v MPSK3169A 200 mg Q8W

82

Pre-specified

2.5

2-sided

Standard error of the mean

4.9

This analysis was performed on Day 169. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=87.

Placebo v MPSK3169A 400 mg Q8W

89

Pre-specified

15.2

2-sided

Standard error of the mean

4.4

This analysis was performed on Day 169. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=103.

Placebo v MPSK3169A 800 mg Q8W

107

Pre-specified

36.2

2-sided

Standard error of the mean

3.8

This analysis was performed on Day 169. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=78.

Placebo v MPSK3169A 800 mg Q12W

83

Pre-specified

8.3

2-sided

Standard error of the mean

5

This analysis was performed at Nadir timepoint. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=111.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

111

Pre-specified

59.8

2-sided

Standard error of the mean

3.2

This analysis was performed at Nadir timepoint. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=81.

MPSK3169A 200 mg Q8W v Placebo

82

Pre-specified

48.2

2-sided

Standard error of the mean

4.2

This analysis was performed at Nadir timepoint. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=88.

MPSK3169A 400 mg Q8W v Placebo

89

Pre-specified

54.4

2-sided

Standard error of the mean

3.8

This analysis was performed at Nadir timepoint. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=107.

MPSK3169A 800 mg Q8W v Placebo

107

Pre-specified

58.8

2-sided

Standard error of the mean

3.2

This analysis was performed at Nadir timepoint. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=83.

MPSK3169A 800 mg Q12W v Placebo

83

Pre-specified

56.6

2-sided

Standard error of the mean

4.1

mITT population participants with baseline and at least 1 post baseline measurement of LDLc concentration were included in the analysis of this end point. "n" value indicates the number of participants evaluable at a specified timepoint for a particular treatment arm.

Secondary

Baseline, Days 8, 15, 22, 29, 43, 57, 71, 85, 99, 113, 120, 141, and 155

This analysis was performed on Day 8. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=110.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

54.2

2-sided

Standard error of the mean

3.8

This analysis was performed on Day 8. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=83.

Placebo v MPSK3169A 200 mg Q8W

86

Pre-specified

51.4

2-sided

Standard error of the mean

4.7

This analysis was performed on Day 8. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDL-c (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=85.

Placebo v MPSK3169A 400 mg Q8W

91

Pre-specified

57.2

2-sided

Standard error of the mean

4.6

This analysis was performed on Day 8. LS mean difference, 95% CIs and p-values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=103.

Placebo v MPSK3169A 800 mg Q8W

112

Pre-specified

56.2

2-sided

Standard error of the mean

3.9

This analysis was performed on Day 8. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=82.

Placebo v MPSK3169A 800 mg Q12W

86

Pre-specified

56.2

2-sided

Standard error of the mean

4.8

This analysis was performed on Day 15. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=111.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

65.7

2-sided

Standard error of the mean

4.2

This analysis was performed on Day 15. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=84.

MPSK3169A 200 mg Q8W v Placebo

86

Pre-specified

53

2-sided

Standard error of the mean

5.3

This analysis was performed on Day 15. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=89.

MPSK3169A 400 mg Q8W v Placebo

91

Pre-specified

64.9

2-sided

Standard error of the mean

5

This analysis was performed on Day 15. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=105.

Placebo v MPSK3169A 800 mg Q8W

112

Pre-specified

69

2-sided

Standard error of the mean

4.3

This analysis was performed on Day 15. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=81.

MPSK3169A 800 mg Q12W v Placebo

86

Pre-specified

66.8

2-sided

Standard error of the mean

5.6

This analysis was performed on Day 22. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=108.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

70.9

2-sided

Standard error of the mean

4.4

This analysis was performed on Day 22. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=84.

MPSK3169A 200 mg Q8W v Placebo

86

Pre-specified

51.3

2-sided

Standard error of the mean

5.5

This analysis was performed on Day 22. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=89.

Placebo v MPSK3169A 400 mg Q8W

91

Pre-specified

71

2-sided

Standard error of the mean

5.1

This analysis was performed on Day 22. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=108.

MPSK3169A 800 mg Q8W v Placebo

112

Pre-specified

73.2

2-sided

Standard error of the mean

4.4

This analysis was performed on Day 22. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=84.

MPSK3169A 800 mg Q12W v Placebo

86

Pre-specified

72.7

2-sided

Standard error of the mean

5.5

This analysis was performed on Day 29. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=112.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

67.2

2-sided

Standard error of the mean

4.6

This analysis was performed on Day 29. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=86.

MPSK3169A 200 mg Q8W v Placebo

86

Pre-specified

36.2

2-sided

Standard error of the mean

5.8

This analysis was performed on Day 29. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=91.

MPSK3169A 400 mg Q8W v Placebo

91

Pre-specified

66.1

2-sided

Standard error of the mean

5.5

This analysis was performed on Day 29. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=112.

MPSK3169A 800 mg Q8W v Placebo

112

Pre-specified

73.7

2-sided

Standard error of the mean

4.6

This analysis was performed on Day 29. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=84.

MPSK3169A 800 mg Q12W v Placebo

86

Pre-specified

76.4

2-sided

Standard error of the mean

6.1

This analysis was performed on Day 43. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=111.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

78.2

2-sided

Standard error of the mean

4.8

This analysis was performed on Day 43. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=83.

MPSK3169A 200 mg Q8W v Placebo

86

Pre-specified

15.6

2-sided

Standard error of the mean

6.1

This analysis was performed on Day 43. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=87.

MPSK3169A 400 mg Q8W v Placebo

91

Pre-specified

53.2

2-sided

Standard error of the mean

5.9

This analysis was performed on Day 43. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=107.

MPSK3169A 800 mg Q8W v Placebo

112

Pre-specified

64.7

2-sided

Standard error of the mean

4.9

This analysis was performed on Day 43. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=84.

MPSK3169A 800 mg Q12W v Placebo

86

Pre-specified

66.4

2-sided

Standard error of the mean

6.1

This analysis was performed on Day 57. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=111.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

71.6

2-sided

Standard error of the mean

4.8

This analysis was performed on Day 57. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=81.

MPSK3169A 200 mg Q8W v Placebo

86

Pre-specified

7

2-sided

Standard error of the mean

6.2

This analysis was performed on Day 57. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=86.

MPSK3169A 400 mg Q8W v Placebo

91

Pre-specified

27.8

2-sided

Standard error of the mean

5.8

This analysis was performed on Day 57. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=106.

MPSK3169A 800 mg Q8W v Placebo

112

Pre-specified

52.2

2-sided

Standard error of the mean

4.9

This analysis was performed on Day 57. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=80.

MPSK3169A 800 mg Q12W v Placebo

86

Pre-specified

61.7

2-sided

Standard error of the mean

6.3

This analysis was performed on Day 71. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=112.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

74

2-sided

Standard error of the mean

4.5

This analysis was performed on Day 71. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=79.

MPSK3169A 200 mg Q8W v Placebo

86

Pre-specified

58.7

2-sided

Standard error of the mean

6.1

This analysis was performed on Day 71. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=86.

MPSK3169A 400 mg Q8W v Placebo

91

Pre-specified

70.6

2-sided

Standard error of the mean

5.5

This analysis was performed on Day 71. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=105.

MPSK3169A 800 mg Q8W v Placebo

112

Pre-specified

73.6

2-sided

Standard error of the mean

4.7

This analysis was performed on Day 71. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=81.

MPSK3169A 800 mg Q12W v Placebo

86

Pre-specified

29.2

2-sided

Standard error of the mean

5.9

This analysis was performed on Day 85. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=114.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

62.4

2-sided

Standard error of the mean

4.9

This analysis was performed on Day 85. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=84.

MPSK3169A 200 mg Q8W v Placebo

86

Pre-specified

37.7

2-sided

Standard error of the mean

6.3

This analysis was performed on Day 85. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=89.

MPSK3169A 400 mg Q8W v Placebo

91

Pre-specified

58.7

2-sided

Standard error of the mean

5.9

This analysis was performed on Day 85. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=108.

MPSK3169A 800 mg Q8W v Placebo

112

Pre-specified

67.3

2-sided

Standard error of the mean

5

This analysis was performed on Day 85. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=83.

MPSK3169A 800 mg Q12W v Placebo

86

Pre-specified

11.3

2-sided

Standard error of the mean

6.4

This analysis was performed on Day 99. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=107.

MPSK3169A 400 mg once every 4 weeks (Q4W) v Placebo

116

Pre-specified

72.1

2-sided

Standard error of the mean

4.7

This analysis was performed on Day 99. LS mean difference, 95% CIs and p−values were based on an analysis of covariance model adjusted for baseline LDLc (<120 mg/dL, ≥120 mg/dL) and diabetes status (yes, no). Number of subjects included in analysis=80.

Placebo v MPSK3169A 200 mg Q8W

86

Pre-specified

11.8

2-sided

Standard error of the mean

5.9