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Trial record 9 of 19 for:    MIPOMERSEN

Safety and Efficacy of Mipomersen in Patients With Severe Hypercholesterolemia on a Maximally Tolerated Lipid-Lowering Regimen and Who Are Not on Apheresis

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ClinicalTrials.gov Identifier: NCT00794664
Recruitment Status : Completed
First Posted : November 20, 2008
Results First Posted : March 21, 2013
Last Update Posted : September 9, 2016
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Kastle Therapeutics, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Hypercholesterolemia
Coronary Heart Disease
Interventions Drug: Mipomersen
Drug: Placebo
Enrollment 58
Recruitment Details  
Pre-assignment Details One hundred and four patients were screened and 58 randomized in a 2:1 treatment arm ratio.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description Weekly subcutaneous injections for 26 weeks 200 mg weekly subcutaneous injections for 26 weeks
Period Title: Treatment Period
Started 19 39
Completed 18 [1] 27 [2]
Not Completed 1 12
Reason Not Completed
Withdrawal by Subject             0             2
Protocol non-compliance             0             1
Not specified             0             1
Adverse Event             1             8
[1]
3 participants enrolled in open-label extension study NCT00694109
[2]
6 participants enrolled in open-label extension study NCT00694109
Period Title: Follow-up Period
Started 16 [1] 33 [1]
Completed 15 28
Not Completed 1 5
Reason Not Completed
Not specified             1             2
Withdrawal by Subject             0             2
Protocol non-compliance             0             1
[1]
Participants enrolled in the open-label extension (NCT00694109) or continued in the follow-up period
Arm/Group Title Placebo Mipomersen Total
Hide Arm/Group Description Weekly subcutaneous injections for 26 weeks 200 mg weekly subcutaneous injections for 26 weeks Total of all reporting groups
Overall Number of Baseline Participants 19 39 58
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 19 participants 39 participants 58 participants
47.9  (13.5) 51.8  (14.3) 50.5  (14.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants 39 participants 58 participants
Female
12
  63.2%
21
  53.8%
33
  56.9%
Male
7
  36.8%
18
  46.2%
25
  43.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 39 participants 58 participants
White 16 33 49
Black 1 2 3
Asian 0 1 1
Multiple 2 1 3
Other 0 2 2
Ethnicity  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 39 participants 58 participants
Not Hispanic or Latino 19 39 58
Hispanic or Latino 0 0 0
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 19 participants 39 participants 58 participants
29.9  (4.10) 28.4  (5.35) 28.9  (4.98)
Waist/hip ratio  
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 19 participants 39 participants 58 participants
0.94  (0.06) 0.92  (0.09) 0.93  (0.08)
Metabolic syndrome   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 39 participants 58 participants
No 10 25 35
Yes 9 14 23
[1]
Measure Description: Yes if 3 or more risk factors are present: 1) Abdominal obesity 2) Triglycerides >=150 mg/dl * 3) High density lipoprotein cholesterol (men <40 mg/dl) (women <50 mg/dl) * 4) Systolic blood pressure >=130 or diastolic >=85 mmHg * 5) Fasting glucose >=100 mg/dl * * = or on medication for condition
Tobacco Use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 39 participants 58 participants
Current 5 4 9
Non-current 7 11 18
Never 7 24 31
Alcohol Use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 19 participants 39 participants 58 participants
Current 7 27 34
Non-current 4 5 9
Never 8 7 15
1.Primary Outcome
Title Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point
Hide Description 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. The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
12.5  (46.87) -35.9  (24.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments Based upon prior clinical study experience with mipomersen, it was estimated that the standard deviation of the percent change in LDL-C was approximately 22%. With 15 patients in the control group and 30 patients in the mipomersen-treated group, this study would have at least 80% power to detect a 20 percentage point difference between the 2 treatment groups. Enrollment was to be conducted such that at least 51 patients were randomized to allow for potential exclusions from an analysis set.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was concluded if p≤0.05
Method t-test, 2 sided
Comments [Not Specified]
2.Primary Outcome
Title LDL-C at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 249.4  (84.3) 276.1  (72.1)
PET 263.9  (102.0) 174.9  (82.8)
3.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
11.41  (36.80) -35.88  (22.95)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Inflation of type 1 error was controlled by specifying a small number of secondary parameters and a sequential inferential approach in which inferential conclusions about each successive parameter required statistical significance of the prior one.
Method t-test, 2 sided
Comments [Not Specified]
4.Secondary Outcome
Title Apo-B at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 182.8  (48.6) 202.1  (49.1)
PET 193.7  (54.2) 126.8  (49.6)
5.Secondary Outcome
Title Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET)
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
11.13  (34.74) -28.31  (20.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Inferential conclusions about this parameter require statistical significance of the previous secondary outcome measure (i.e., percent change from baseline in Apo B at PET).
Method t-test, 2 sided
Comments [Not Specified]
6.Secondary Outcome
Title Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 320.6  (87.2) 356.8  (77.0)
PET 341.5  (100.5) 251.5  (82.2)
7.Secondary Outcome
Title Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET)
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
14.17  (47.75) -33.95  (23.80)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Inferential conclusions about this parameter require statistical significance of the previous secondary outcome measure (i.e., percent change from baseline in total cholesterol at PET).
Method t-test, 2 sided
Comments [Not Specified]
8.Secondary Outcome
Title Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 277.5  (88.3) 305.6  (78.3)
PET 296.7  (103.8) 198.1  (85.3)
9.Other Pre-specified Outcome
Title Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET)
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
26.50  (60.61) -8.71  (40.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments Statistical significance was concluded if p ≤0.05
Method t-test, 2 sided
Comments [Not Specified]
10.Other Pre-specified Outcome
Title Triglycerides at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 140.3  (49.8) 142.2  (86.0)
PET 164.5  (61.2) 116.3  (63.3)
11.Other Pre-specified Outcome
Title Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET)
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-1.46  (25.74) -32.65  (32.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was concluded if p ≤0.05
Method t-test, 2 sided
Comments [Not Specified]
12.Other Pre-specified Outcome
Title Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 32.4  (28.5) 61.3  (68.4)
PET 32.1  (28.1) 43.3  (54.3)
13.Other Pre-specified Outcome
Title Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET)
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
25.13  (58.66) -9.36  (39.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.032
Comments Statistical significance was concluded if p ≤0.05
Method t-test, 2 sided
Comments [Not Specified]
14.Other Pre-specified Outcome
Title VLDL-C at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 28.1  (9.9) 29.1  (20.0)
PET 32.8  (12.3) 23.2  (12.6)
15.Other Pre-specified Outcome
Title 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)
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Median (Inter-Quartile Range)
Unit of Measure: percentage of baseline
1.9
(-14.3 to 18.0)
-41.8
(-57.4 to -16.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Statistical significance was concluded if p ≤0.05
Method Wilcoxon rank sum test
Comments [Not Specified]
16.Other Pre-specified Outcome
Title Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Median (Inter-Quartile Range)
Unit of Measure: ratio
Baseline
5.89
(3.89 to 6.58)
5.21
(4.13 to 6.97)
PET
5.85
(3.28 to 7.76)
3.05
(2.11 to 4.26)
17.Other Pre-specified Outcome
Title Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET)
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
1.75  (14.33) -3.04  (15.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments Statistical significance was concluded if p ≤0.05
Method t-test, 2 sided
Comments [Not Specified]
18.Other Pre-specified Outcome
Title Apo-A1 at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 139.2  (32.6) 154.9  (31.4)
PET 140.7  (34.2) 147.9  (27.0)
19.Other Pre-specified Outcome
Title Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET)
Hide Description 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.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
3.16  (16.50) 5.78  (21.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.647
Comments Statistical significance was concluded if p ≤0.05
Method t-test, 2 sided
Comments [Not Specified]
20.Other Pre-specified Outcome
Title HDL-C at Baseline and the Primary Efficacy Time Point (PET)
Hide Description The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
Weekly subcutaneous injections for 26 weeks
200 mg weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 18 39
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 43.1  (11.6) 51.1  (15.1)
PET 44.8  (16.3) 53.4  (16.7)
Time Frame 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.
Adverse Event Reporting Description 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.
 
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description Weekly subcutaneous injections for 26 weeks 200 mg weekly subcutaneous injections for 26 weeks
All-Cause Mortality
Placebo Mipomersen
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Mipomersen
Affected / at Risk (%) Affected / at Risk (%)
Total   0/19 (0.00%)   6/39 (15.38%) 
Cardiac disorders     
Acute myocardial infarction  1  0/19 (0.00%)  1/39 (2.56%) 
Angina pectoris  1  0/19 (0.00%)  1/39 (2.56%) 
Angina unstable  1  0/19 (0.00%)  1/39 (2.56%) 
Cardiac failure  1  0/19 (0.00%)  1/39 (2.56%) 
Prinzmetal angina  1  0/19 (0.00%)  1/39 (2.56%) 
General disorders     
Device malfunction  1  0/19 (0.00%)  1/39 (2.56%) 
Hepatobiliary disorders     
Hepatic steatosis  1  0/19 (0.00%)  1/39 (2.56%) 
Investigations     
Alanine aminotransferase increased  1  0/19 (0.00%)  1/39 (2.56%) 
Aspartate aminotransferase increased  1  0/19 (0.00%)  1/39 (2.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Mipomersen
Affected / at Risk (%) Affected / at Risk (%)
Total   16/19 (84.21%)   39/39 (100.00%) 
Cardiac disorders     
Angina pectoris  1  1/19 (5.26%)  1/39 (2.56%) 
Coronary artery disease  1  0/19 (0.00%)  1/39 (2.56%) 
Supraventricular extrasystoles  1  0/19 (0.00%)  1/39 (2.56%) 
Ear and labyrinth disorders     
Tinnitus  1  0/19 (0.00%)  1/39 (2.56%) 
Eye disorders     
Eye swelling  1  0/19 (0.00%)  1/39 (2.56%) 
Vitreous floaters  1  0/19 (0.00%)  1/39 (2.56%) 
Gastrointestinal disorders     
Abdominal pain  1  0/19 (0.00%)  2/39 (5.13%) 
Abdominal pain upper  1  1/19 (5.26%)  2/39 (5.13%) 
Constipation  1  0/19 (0.00%)  1/39 (2.56%) 
Diarrhoea  1  1/19 (5.26%)  1/39 (2.56%) 
Gastritis  1  0/19 (0.00%)  1/39 (2.56%) 
Gastrooesophageal reflux disease  1  0/19 (0.00%)  1/39 (2.56%) 
Nausea  1  0/19 (0.00%)  5/39 (12.82%) 
Rectal haemorrhage  1  0/19 (0.00%)  1/39 (2.56%) 
Vomiting  1  0/19 (0.00%)  1/39 (2.56%) 
General disorders     
Asthenia  1  0/19 (0.00%)  1/39 (2.56%) 
Chest discomfort  1  1/19 (5.26%)  0/39 (0.00%) 
Chills  1  0/19 (0.00%)  1/39 (2.56%) 
Fatigue  1  2/19 (10.53%)  4/39 (10.26%) 
Influenza like illness  1  0/19 (0.00%)  9/39 (23.08%) 
Injection site discolouration  1  0/19 (0.00%)  3/39 (7.69%) 
Injection site erythema  1  2/19 (10.53%)  22/39 (56.41%) 
Injection site haematoma  1  4/19 (21.05%)  9/39 (23.08%) 
Injection site induration  1  0/19 (0.00%)  3/39 (7.69%) 
Injection site inflammation  1  0/19 (0.00%)  3/39 (7.69%) 
Injection site mass  1  0/19 (0.00%)  1/39 (2.56%) 
Injection site nodule  1  0/19 (0.00%)  1/39 (2.56%) 
Injection site oedema  1  0/19 (0.00%)  5/39 (12.82%) 
Injection site pain  1  0/19 (0.00%)  23/39 (58.97%) 
Injection site papule  1  0/19 (0.00%)  1/39 (2.56%) 
Injection site pruritus  1  1/19 (5.26%)  13/39 (33.33%) 
Injection site rash  1  0/19 (0.00%)  3/39 (7.69%) 
Injection site reaction  1  0/19 (0.00%)  2/39 (5.13%) 
Injection site recall reaction  1  0/19 (0.00%)  2/39 (5.13%) 
Injection site swelling  1  0/19 (0.00%)  12/39 (30.77%) 
Injection site urticaria  1  0/19 (0.00%)  1/39 (2.56%) 
Injection site vesicles  1  0/19 (0.00%)  1/39 (2.56%) 
Non-cardiac chest pain  1  0/19 (0.00%)  1/39 (2.56%) 
Oedema peripheral  1  0/19 (0.00%)  2/39 (5.13%) 
Pain  1  1/19 (5.26%)  0/39 (0.00%) 
Pyrexia  1  0/19 (0.00%)  3/39 (7.69%) 
Hepatobiliary disorders     
Hepatic function abnormal  1  0/19 (0.00%)  1/39 (2.56%) 
Hepatic steatosis  1  0/19 (0.00%)  4/39 (10.26%) 
Liver tenderness  1  0/19 (0.00%)  1/39 (2.56%) 
Immune system disorders     
Allergy to plants  1  0/19 (0.00%)  1/39 (2.56%) 
Infections and infestations     
Cellulitis  1  0/19 (0.00%)  1/39 (2.56%) 
Gastroenteritis  1  1/19 (5.26%)  2/39 (5.13%) 
Gastroenteritis viral  1  0/19 (0.00%)  1/39 (2.56%) 
Hordeolum  1  0/19 (0.00%)  1/39 (2.56%) 
Impetigo  1  0/19 (0.00%)  1/39 (2.56%) 
Influenza  1  0/19 (0.00%)  1/39 (2.56%) 
Lower respiratory tract infection  1  1/19 (5.26%)  0/39 (0.00%) 
Nasopharyngitis  1  1/19 (5.26%)  4/39 (10.26%) 
Onychomycosis  1  0/19 (0.00%)  1/39 (2.56%) 
Pharyngitis  1  0/19 (0.00%)  1/39 (2.56%) 
Pleurisy viral  1  0/19 (0.00%)  1/39 (2.56%) 
Pyelonephritis  1  0/19 (0.00%)  1/39 (2.56%) 
Sinusitis  1  0/19 (0.00%)  1/39 (2.56%) 
Skin infection  1  0/19 (0.00%)  1/39 (2.56%) 
Upper respiratory tract infection  1  0/19 (0.00%)  1/39 (2.56%) 
Urinary tract infection  1  1/19 (5.26%)  3/39 (7.69%) 
Viral upper respiratory tract infection  1  0/19 (0.00%)  1/39 (2.56%) 
Injury, poisoning and procedural complications     
Animal bite  1  0/19 (0.00%)  1/39 (2.56%) 
Animal scratch  1  0/19 (0.00%)  1/39 (2.56%) 
Arthropod bite  1  0/19 (0.00%)  1/39 (2.56%) 
Contusion  1  1/19 (5.26%)  1/39 (2.56%) 
Epicondylitis  1  0/19 (0.00%)  1/39 (2.56%) 
Post procedural complication  1  0/19 (0.00%)  1/39 (2.56%) 
Post procedural haematoma  1  0/19 (0.00%)  1/39 (2.56%) 
Investigations     
Alanine aminotransferase increased  1  0/19 (0.00%)  7/39 (17.95%) 
Aspartate aminotransferase increased  1  0/19 (0.00%)  4/39 (10.26%) 
Blood alkaline phosphatase increased  1  0/19 (0.00%)  1/39 (2.56%) 
Blood creatine phosphokinase increased  1  1/19 (5.26%)  1/39 (2.56%) 
Blood creatinine increased  1  0/19 (0.00%)  3/39 (7.69%) 
Blood lactate dehydrogenase increased  1  0/19 (0.00%)  2/39 (5.13%) 
Cardiac murmur  1  0/19 (0.00%)  1/39 (2.56%) 
Electrocardiogram PR prolongation  1  0/19 (0.00%)  1/39 (2.56%) 
Epstein-Barr virus antibody positive  1  0/19 (0.00%)  1/39 (2.56%) 
Hepatic enzyme increased  1  0/19 (0.00%)  1/39 (2.56%) 
Liver function test abnormal  1  0/19 (0.00%)  1/39 (2.56%) 
Platelet count decreased  1  1/19 (5.26%)  0/39 (0.00%) 
Prothrombin time prolonged  1  1/19 (5.26%)  0/39 (0.00%) 
Weight increased  1  0/19 (0.00%)  1/39 (2.56%) 
Metabolism and nutrition disorders     
Glucose tolerance impaired  1  0/19 (0.00%)  1/39 (2.56%) 
Hyperuricaemia  1  1/19 (5.26%)  0/39 (0.00%) 
Type 2 diabetes mellitus  1  1/19 (5.26%)  0/39 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/19 (5.26%)  1/39 (2.56%) 
Arthritis  1  0/19 (0.00%)  1/39 (2.56%) 
Back pain  1  0/19 (0.00%)  1/39 (2.56%) 
Groin pain  1  0/19 (0.00%)  2/39 (5.13%) 
Intervertebral disc protrusion  1  0/19 (0.00%)  1/39 (2.56%) 
Muscle spasms  1  0/19 (0.00%)  1/39 (2.56%) 
Musculoskeletal pain  1  0/19 (0.00%)  1/39 (2.56%) 
Musculoskeletal stiffness  1  1/19 (5.26%)  0/39 (0.00%) 
Myalgia  1  1/19 (5.26%)  3/39 (7.69%) 
Osteoarthritis  1  0/19 (0.00%)  1/39 (2.56%) 
Osteochondrosis  1  0/19 (0.00%)  1/39 (2.56%) 
Pain in extremity  1  1/19 (5.26%)  3/39 (7.69%) 
Pain in jaw  1  0/19 (0.00%)  1/39 (2.56%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign breast neoplasm  1  0/19 (0.00%)  1/39 (2.56%) 
Nervous system disorders     
Cerebrovascular accident  1  0/19 (0.00%)  1/39 (2.56%) 
Dizziness  1  0/19 (0.00%)  2/39 (5.13%) 
Headache  1  1/19 (5.26%)  1/39 (2.56%) 
Lethargy  1  0/19 (0.00%)  1/39 (2.56%) 
Migraine  1  1/19 (5.26%)  1/39 (2.56%) 
Restless legs syndrome  1  1/19 (5.26%)  0/39 (0.00%) 
Somnolence  1  0/19 (0.00%)  1/39 (2.56%) 
Syncope  1  0/19 (0.00%)  2/39 (5.13%) 
Tremor  1  0/19 (0.00%)  1/39 (2.56%) 
Psychiatric disorders     
Anxiety  1  0/19 (0.00%)  1/39 (2.56%) 
Bipolar disorder  1  0/19 (0.00%)  1/39 (2.56%) 
Depression  1  0/19 (0.00%)  1/39 (2.56%) 
Insomnia  1  0/19 (0.00%)  1/39 (2.56%) 
Renal and urinary disorders     
Proteinuria  1  1/19 (5.26%)  2/39 (5.13%) 
Renal cyst  1  0/19 (0.00%)  1/39 (2.56%) 
Respiratory, thoracic and mediastinal disorders     
Bronchitis chronic  1  0/19 (0.00%)  1/39 (2.56%) 
Cough  1  0/19 (0.00%)  2/39 (5.13%) 
Dyspnoea  1  0/19 (0.00%)  1/39 (2.56%) 
Dyspnoea exertional  1  0/19 (0.00%)  1/39 (2.56%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  0/19 (0.00%)  1/39 (2.56%) 
Blister  1  1/19 (5.26%)  0/39 (0.00%) 
Dermatitis  1  0/19 (0.00%)  1/39 (2.56%) 
Dermatitis allergic  1  1/19 (5.26%)  1/39 (2.56%) 
Ecchymosis  1  0/19 (0.00%)  1/39 (2.56%) 
Hyperkeratosis  1  0/19 (0.00%)  1/39 (2.56%) 
Pruritus  1  1/19 (5.26%)  0/39 (0.00%) 
Xanthoma  1  0/19 (0.00%)  1/39 (2.56%) 
Vascular disorders     
Flushing  1  0/19 (0.00%)  1/39 (2.56%) 
Hot flush  1  0/19 (0.00%)  1/39 (2.56%) 
Hypertension  1  0/19 (0.00%)  3/39 (7.69%) 
Orthostatic hypotension  1  0/19 (0.00%)  1/39 (2.56%) 
Peripheral arterial occlusive disease  1  0/19 (0.00%)  1/39 (2.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
In multi-site studies, PI can publish site data after a multi-centered publication or 12 months after study completion. PI gives Genzyme a draft 60 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 6 months (contracts have variable timeframes) upon notifying PI that it will file a patent application on inventions contained in the draft.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Genzyme Medical Information
Organization: Genzyme Corporation
Phone: 617-252-7832
Layout table for additonal information
Responsible Party: Kastle Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT00794664     History of Changes
Other Study ID Numbers: MIPO3500108
2008-006020-53 ( EudraCT Number )
First Submitted: November 19, 2008
First Posted: November 20, 2008
Results First Submitted: February 15, 2013
Results First Posted: March 21, 2013
Last Update Posted: September 9, 2016