Trial Outcomes & Findings for Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia (NCT NCT00607373)

Last Updated: 2016-09-09

Results Overview

LDL-C was measured in mg/dL. Samples were taken following an overnight fast. For patients with triglycerides \<400 mg/dL, LDL-C was obtained using Friedewald's calculation; and for patients with triglycerides \>=400 mg/dL, LDL-C was directly measured by the central laboratory using ultracentrifugation. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. If the Study Day 1 and screening LDL-C values were \>12% different (relative to the maximum value), then the screening value was not used, because the Study Day 1 value represents the best estimate of the patient's condition at the beginning of study drug administration. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

51 participants

Primary outcome timeframe

Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Results posted on

2016-09-09

Participant Flow

Sixty-one patients were screened and fifty-one randomized. Eligible patients were randomized in a 2:1 ratio to receive 200 mg mipomersen or matching volume placebo subcutaneous (SC) injections weekly.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Treatment Period STARTED	17	34
Treatment Period COMPLETED	17	28
Treatment Period NOT COMPLETED	0	6
Follow-up Period STARTED	1	11
Follow-up Period COMPLETED	0	6
Follow-up Period NOT COMPLETED	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Treatment Period Adverse Event	0	4
Treatment Period Physician Decision	0	1
Treatment Period Withdrawal by Subject	0	1
Follow-up Period Other	0	1
Follow-up Period Protocol Violation	0	1
Follow-up Period Withdrawal by Subject	1	3

Baseline Characteristics

Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.	Total n=51 Participants Total of all reporting groups
Age, Continuous	33.0 years STANDARD_DEVIATION 14.1 • n=5 Participants	30.4 years STANDARD_DEVIATION 11.5 • n=7 Participants	31.3 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	19 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	15 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	16 participants n=5 Participants	29 participants n=7 Participants	45 participants n=5 Participants
Race/Ethnicity, Customized White	13 participants n=5 Participants	25 participants n=7 Participants	38 participants n=5 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	8 participants n=7 Participants	11 participants n=5 Participants
Race/Ethnicity, Customized Black	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Body Mass Index	26.32 kg/m^2 STANDARD_DEVIATION 4.41 • n=5 Participants	25.97 kg/m^2 STANDARD_DEVIATION 5.81 • n=7 Participants	26.08 kg/m^2 STANDARD_DEVIATION 5.34 • n=5 Participants
Waist/hip ratio	0.83 ratio STANDARD_DEVIATION 0.07 • n=5 Participants	0.85 ratio STANDARD_DEVIATION 0.06 • n=7 Participants	0.84 ratio STANDARD_DEVIATION 0.07 • n=5 Participants
Metabolic syndrome No	16 participants n=5 Participants	27 participants n=7 Participants	43 participants n=5 Participants
Metabolic syndrome Yes	1 participants n=5 Participants	7 participants n=7 Participants	8 participants n=5 Participants
Tobacco Use Current	3 participants n=5 Participants	7 participants n=7 Participants	10 participants n=5 Participants
Tobacco Use Non-current	3 participants n=5 Participants	4 participants n=7 Participants	7 participants n=5 Participants
Tobacco Use Never	11 participants n=5 Participants	23 participants n=7 Participants	34 participants n=5 Participants
Alcohol Use Current	6 participants n=5 Participants	14 participants n=7 Participants	20 participants n=5 Participants
Alcohol Use Non-current	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Alcohol Use Never	8 participants n=5 Participants	17 participants n=7 Participants	25 participants n=5 Participants
Fasting serum insulin	9.72 microIU/mL STANDARD_DEVIATION 5.98 • n=5 Participants	11.54 microIU/mL STANDARD_DEVIATION 14.78 • n=7 Participants	10.93 microIU/mL STANDARD_DEVIATION 12.51 • n=5 Participants
Fasting hemoglobin A1c	5.47 percentage of total hemoglobin STANDARD_DEVIATION 0.22 • n=5 Participants	5.34 percentage of total hemoglobin STANDARD_DEVIATION 0.37 • n=7 Participants	5.38 percentage of total hemoglobin STANDARD_DEVIATION 0.33 • n=5 Participants
Weight <50 kg	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Weight >=50 kg	15 participants n=5 Participants	30 participants n=7 Participants	45 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set (FAS). The FAS, which represents the practically-feasible intent-to-treat (ITT) population as delineated in ICH Guideline E9, consists of treated participants with a valid baseline and at least one post-baseline LDL-C measure.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point	-3.31 percentage of baseline Standard Deviation 17.06	-24.66 percentage of baseline Standard Deviation 19.85

PRIMARY outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
LDL-C at Baseline and the Primary Efficacy Time Point (PET) Baseline	400.2 mg/dL Standard Deviation 141.5	438.9 mg/dL Standard Deviation 138.6
LDL-C at Baseline and the Primary Efficacy Time Point (PET) PET	388.2 mg/dL Standard Deviation 150.5	326.2 mg/dL Standard Deviation 121.3

SECONDARY outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

Apo-B was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point	-2.54 percentage of baseline Standard Deviation 12.56	-26.77 percentage of baseline Standard Deviation 17.04

SECONDARY outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 )

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Apo-B at Baseline and the Primary Efficacy Time Point (PET) Baseline	259.2 mg/dL Standard Deviation 84.4	283.1 mg/dL Standard Deviation 78.4
Apo-B at Baseline and the Primary Efficacy Time Point (PET) PET	252.6 mg/dL Standard Deviation 85.0	205.4 mg/dL Standard Deviation 70.0

SECONDARY outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET)	-1.98 percentage of baseline Standard Deviation 14.82	-21.20 percentage of baseline Standard Deviation 17.69

SECONDARY outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) Baseline	460.5 mg/dL Standard Deviation 132.0	502.4 mg/dL Standard Deviation 144.5
Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) PET	452.1 mg/dL Standard Deviation 144.6	389.7 mg/dL Standard Deviation 125.3

SECONDARY outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

Non-HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET)	-2.90 percentage of baseline Standard Deviation 16.32	-24.50 percentage of baseline Standard Deviation 19.17

SECONDARY outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) PET	409.1 mg/dL Standard Deviation 156.6	345.8 mg/dL Standard Deviation 126.6
Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) Baseline	418.9 mg/dL Standard Deviation 144.5	464.3 mg/dL Standard Deviation 145.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET)	0.9 percentage of baseline Interval -25.0 to 29.5	-17.5 percentage of baseline Interval -36.0 to -4.8

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Triglycerides at Baseline and the Primary Efficacy Time Point (PET) Baseline	92 mg/dL Interval 80.0 to 105.0	91 mg/dL Interval 73.0 to 141.0
Triglycerides at Baseline and the Primary Efficacy Time Point (PET) PET	85 mg/dL Interval 65.0 to 117.0	76 mg/dL Interval 52.0 to 116.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

Lipoprotein(a) was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET)	-7.87 percentage of baseline Standard Deviation 21.87	-31.10 percentage of baseline Standard Deviation 23.02

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) Baseline	66.3 mg/dL Standard Deviation 53.1	64.3 mg/dL Standard Deviation 41.0
Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) PET	61.6 mg/dL Standard Deviation 52.6	43.8 mg/dL Standard Deviation 32.1

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

VLDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET)	2.3 percentage of baseline Interval -25.0 to 28.6	-17.3 percentage of baseline Interval -37.1 to -3.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
VLDL-C at Baseline and the Primary Efficacy Time Point (PET) Baseline	18 mg/dL Interval 16.0 to 21.0	18 mg/dL Interval 15.0 to 28.0
VLDL-C at Baseline and the Primary Efficacy Time Point (PET) PET	17 mg/dL Interval 13.0 to 23.0	15 mg/dL Interval 10.0 to 23.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

LDL-C and HDL-C were measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Change From Baseline in Ratio of Low-density Lipoprotein Cholesterol (LDL-C) to High-density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)	-6.22 percentage of baseline Standard Deviation 18.81	-34.32 percentage of baseline Standard Deviation 21.00

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) Baseline	12.14 ratio Standard Deviation 7.675	13.02 ratio Standard Deviation 6.115
Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) PET	11.37 ratio Standard Deviation 7.095	8.13 ratio Standard Deviation 3.921

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

Apo-A1 was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET)	5.35 percentage of baseline Standard Deviation 10.63	9.27 percentage of baseline Standard Deviation 17.59

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) Baseline	118.6 mg/dL Standard Deviation 33.0	111.5 mg/dL Standard Deviation 27.9
Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) PET	124.5 mg/dL Standard Deviation 34.9	118.8 mg/dL Standard Deviation 20.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

HDL-C was measured in mg/dL. Samples were taken following an overnight fast. Baseline was defined as the average of the screening and Study Day 1 (pre-treatment) assessments. An assessment was not included in this calculation if it was associated with a non-fasting blood draw or was drawn more than 4 weeks prior to Study Day 1. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)	4.1 percentage of baseline Interval -2.0 to 13.2	14.8 percentage of baseline Interval 3.3 to 27.0

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28

Population: Full analysis set

The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=17 Participants Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 Participants Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
HDL-C at Baseline and the Primary Efficacy Time Point (PET) Baseline	38 mg/dL Interval 27.0 to 49.0	35 mg/dL Interval 32.0 to 44.0
HDL-C at Baseline and the Primary Efficacy Time Point (PET) PET	43 mg/dL Interval 28.0 to 53.0	43 mg/dL Interval 37.0 to 48.0

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Mipomersen

Serious events: 2 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=17 participants at risk Participants received placebo as a subcutaneous injection once a week for 26 weeks	Mipomersen n=34 participants at risk Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Cardiac disorders Acute coronary syndrome	0.00% 0/17 • Day 1 to week 28. On-treatment AEs started on/after the first study drug dose and on/before the end of the treatment period. The treatment period was the time study drug was administered until the later of the PET or 14 days after last study drug dose. The Safety Set includes all randomized patients who receive at least 1 injection of the study treatment. In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.	2.9% 1/34 • Day 1 to week 28. On-treatment AEs started on/after the first study drug dose and on/before the end of the treatment period. The treatment period was the time study drug was administered until the later of the PET or 14 days after last study drug dose. The Safety Set includes all randomized patients who receive at least 1 injection of the study treatment. In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/17 • Day 1 to week 28. On-treatment AEs started on/after the first study drug dose and on/before the end of the treatment period. The treatment period was the time study drug was administered until the later of the PET or 14 days after last study drug dose. The Safety Set includes all randomized patients who receive at least 1 injection of the study treatment. In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.	2.9% 1/34 • Day 1 to week 28. On-treatment AEs started on/after the first study drug dose and on/before the end of the treatment period. The treatment period was the time study drug was administered until the later of the PET or 14 days after last study drug dose. The Safety Set includes all randomized patients who receive at least 1 injection of the study treatment. In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
Renal and urinary disorders Nephrolithiasis	5.9% 1/17 • Day 1 to week 28. On-treatment AEs started on/after the first study drug dose and on/before the end of the treatment period. The treatment period was the time study drug was administered until the later of the PET or 14 days after last study drug dose. The Safety Set includes all randomized patients who receive at least 1 injection of the study treatment. In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.	0.00% 0/34 • Day 1 to week 28. On-treatment AEs started on/after the first study drug dose and on/before the end of the treatment period. The treatment period was the time study drug was administered until the later of the PET or 14 days after last study drug dose. The Safety Set includes all randomized patients who receive at least 1 injection of the study treatment. In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.

Other adverse events

Additional Information

Genzyme Medical Information

Genzyme Corporation

Phone: 617-252-7832

Results disclosure agreements

Principal investigator is a sponsor employee The first publication for a multi-centre trial must address all centers. Institution will submit for review a proposed publication or presentation at least 60 days prior to submission date. Sponsor has the right to delay publication or presentation for not more than 6 months (contracts have variable timeframes) to address patent applications. Sponsor also has the right to demand in writing the deletion of confidential information, as long as such removal will not preclude publication.
Publication restrictions are in place

Restriction type: OTHER