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Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia (RADICHOL 1)

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ClinicalTrials.gov Identifier: NCT00607373
Recruitment Status : Completed
First Posted : February 5, 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 Lipid Metabolism, Inborn Errors
Hypercholesterolemia, Autosomal Dominant
Hyperlipidemias
Metabolic Diseases
Hyperlipoproteinemia Type II
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Metabolic Disorder
Congenital Abnormalities
Hypercholesterolemia
Hyperlipoproteinemias
Dyslipidemias
Lipid Metabolism Disorders
Interventions Drug: mipomersen
Drug: Placebo
Enrollment 51
Recruitment Details  
Pre-assignment Details 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.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description Participants received placebo as a subcutaneous injection once a week for 26 weeks Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Period Title: Treatment Period
Started 17 34
Completed 17 [1] 28 [2]
Not Completed 0 6
Reason Not Completed
Adverse Event             0             4
Physician Decision             0             1
Withdrawal by Subject             0             1
[1]
16 enrolled in open-label extension study NCT00694109
[2]
23 enrolled in open-label extension study NCT00694109
Period Title: Follow-up Period
Started 1 [1] 11 [1]
Completed 0 6
Not Completed 1 5
Reason Not Completed
Not specified             0             1
Protocol Violation             0             1
Withdrawal by Subject             1             3
[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 Participants received placebo as a subcutaneous injection once a week for 26 weeks Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. Total of all reporting groups
Overall Number of Baseline Participants 17 34 51
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 34 participants 51 participants
33.0  (14.1) 30.4  (11.5) 31.3  (12.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 34 participants 51 participants
Female
10
  58.8%
19
  55.9%
29
  56.9%
Male
7
  41.2%
15
  44.1%
22
  43.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 34 participants 51 participants
Hispanic or Latino 1 5 6
Not Hispanic or Latino 16 29 45
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 34 participants 51 participants
White 13 25 38
Asian 3 8 11
Black 1 1 2
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 17 participants 34 participants 51 participants
26.32  (4.41) 25.97  (5.81) 26.08  (5.34)
Waist/hip ratio  
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 17 participants 34 participants 51 participants
0.83  (0.07) 0.85  (0.06) 0.84  (0.07)
Metabolic syndrome   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 34 participants 51 participants
No 16 27 43
Yes 1 7 8
[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 17 participants 34 participants 51 participants
Current 3 7 10
Non-current 3 4 7
Never 11 23 34
Alcohol Use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 34 participants 51 participants
Current 6 14 20
Non-current 3 3 6
Never 8 17 25
Fasting serum insulin  
Mean (Standard Deviation)
Unit of measure:  microIU/mL
Number Analyzed 17 participants 34 participants 51 participants
9.72  (5.98) 11.54  (14.78) 10.93  (12.51)
Fasting hemoglobin A1c  
Mean (Standard Deviation)
Unit of measure:  Percentage of total hemoglobin
Number Analyzed 17 participants 34 participants 51 participants
5.47  (0.22) 5.34  (0.37) 5.38  (0.33)
Weight   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 34 participants 51 participants
<50 kg 2 4 6
>=50 kg 15 30 45
[1]
Measure Description: Participants who weighed <50 kg received the lower dose of 160 mg mipomersen or matching placebo. All other patients received a dose of 200 mg or matching placebo.
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. 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.
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-3.31  (17.06) -24.66  (19.85)
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 is 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. Fifty-one patients were enrolled to allow for patient withdrawals and potential exclusions from analysis sets.
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 400.2  (141.5) 438.9  (138.6)
PET 388.2  (150.5) 326.2  (121.3)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-2.54  (12.56) -26.77  (17.04)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 259.2  (84.4) 283.1  (78.4)
PET 252.6  (85.0) 205.4  (70.0)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-1.98  (14.82) -21.20  (17.69)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 460.5  (132.0) 502.4  (144.5)
PET 452.1  (144.6) 389.7  (125.3)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-2.90  (16.32) -24.50  (19.17)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 418.9  (144.5) 464.3  (145.4)
PET 409.1  (156.6) 345.8  (126.6)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Median (Inter-Quartile Range)
Unit of Measure: percentage of baseline
0.9
(-25.0 to 29.5)
-17.5
(-36.0 to -4.8)
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 0.013
Comments Statistical significance was concluded if p ≤0.05
Method Wilcoxon rank sum test
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
Baseline
92
(80 to 105)
91
(73 to 141)
PET
85
(65 to 117)
76
(52 to 116)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-7.87  (21.87) -31.10  (23.02)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 66.3  (53.1) 64.3  (41.0)
PET 61.6  (52.6) 43.8  (32.1)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Median (Inter-Quartile Range)
Unit of Measure: percentage of baseline
2.3
(-25.0 to 28.6)
-17.3
(-37.1 to -3.0)
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 0.009
Comments Statistical significance was concluded if p ≤0.05
Method Wilcoxon rank sum test
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
Baseline
18
(16 to 21)
18
(15 to 28)
PET
17
(13 to 23)
15
(10 to 23)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-6.22  (18.81) -34.32  (21.00)
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]
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: ratio
Baseline 12.14  (7.675) 13.02  (6.115)
PET 11.37  (7.095) 8.13  (3.921)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
5.35  (10.63) 9.27  (17.59)
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 0.328
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 118.6  (33.0) 111.5  (27.9)
PET 124.5  (34.9) 118.8  (20.5)
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Median (Inter-Quartile Range)
Unit of Measure: percentage of baseline
4.1
(-2.0 to 13.2)
14.8
(3.3 to 27.0)
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 0.035
Comments Statistical significance was concluded if p ≤0.05
Method Wilcoxon rank sum test
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:
Participants received placebo as a subcutaneous injection once a week for 26 weeks
Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks.
Overall Number of Participants Analyzed 17 34
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
Baseline
38
(27 to 49)
35
(32 to 44)
PET
43
(28 to 53)
43
(37 to 48)
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 Participants received placebo as a subcutaneous injection once a week for 26 weeks Participants received mipomersen 200 mg as a subcutaneous injection once a week 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   1/17 (5.88%)   2/34 (5.88%) 
Cardiac disorders     
Acute coronary syndrome  1  0/17 (0.00%)  1/34 (2.94%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  0/17 (0.00%)  1/34 (2.94%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/17 (5.88%)  0/34 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
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   13/17 (76.47%)   30/34 (88.24%) 
Blood and lymphatic system disorders     
Anaemia  1  1/17 (5.88%)  2/34 (5.88%) 
Cardiac disorders     
Angina pectoris  1  0/17 (0.00%)  1/34 (2.94%) 
Aortic valve disease  1  0/17 (0.00%)  1/34 (2.94%) 
Cardiac discomfort  1  0/17 (0.00%)  1/34 (2.94%) 
Palpitations  1  0/17 (0.00%)  1/34 (2.94%) 
Ear and labyrinth disorders     
Ear pain  1  0/17 (0.00%)  1/34 (2.94%) 
Endocrine disorders     
Hypothyroidism  1  1/17 (5.88%)  1/34 (2.94%) 
Gastrointestinal disorders     
Abdominal pain  1  0/17 (0.00%)  2/34 (5.88%) 
Abdominal pain upper  1  0/17 (0.00%)  1/34 (2.94%) 
Constipation  1  1/17 (5.88%)  2/34 (5.88%) 
Diarrhoea  1  0/17 (0.00%)  1/34 (2.94%) 
Dry mouth  1  1/17 (5.88%)  0/34 (0.00%) 
Dyspepsia  1  0/17 (0.00%)  1/34 (2.94%) 
Gastrooesophageal reflux disease  1  0/17 (0.00%)  1/34 (2.94%) 
Nausea  1  1/17 (5.88%)  6/34 (17.65%) 
Toothache  1  0/17 (0.00%)  1/34 (2.94%) 
Vomiting  1  1/17 (5.88%)  0/34 (0.00%) 
General disorders     
Asthenia  1  0/17 (0.00%)  1/34 (2.94%) 
Chest pain  1  0/17 (0.00%)  4/34 (11.76%) 
Chills  1  0/17 (0.00%)  1/34 (2.94%) 
Fatigue  1  0/17 (0.00%)  1/34 (2.94%) 
Influenza like illness  1  0/17 (0.00%)  3/34 (8.82%) 
Injection site anaesthesia  1  0/17 (0.00%)  1/34 (2.94%) 
Injection site discolouration  1  0/17 (0.00%)  10/34 (29.41%) 
Injection site discomfort  1  0/17 (0.00%)  3/34 (8.82%) 
Injection site erythema  1  1/17 (5.88%)  19/34 (55.88%) 
Injection site haematoma  1  2/17 (11.76%)  12/34 (35.29%) 
Injection site haemorrhage  1  0/17 (0.00%)  1/34 (2.94%) 
Injection site induration  1  0/17 (0.00%)  2/34 (5.88%) 
Injection site inflammation  1  0/17 (0.00%)  1/34 (2.94%) 
Injection site irritation  1  1/17 (5.88%)  1/34 (2.94%) 
Injection site macule  1  0/17 (0.00%)  5/34 (14.71%) 
Injection site oedema  1  0/17 (0.00%)  2/34 (5.88%) 
Injection site pain  1  1/17 (5.88%)  12/34 (35.29%) 
Injection site pallor  1  0/17 (0.00%)  2/34 (5.88%) 
Injection site papule  1  0/17 (0.00%)  4/34 (11.76%) 
Injection site paraesthesia  1  0/17 (0.00%)  1/34 (2.94%) 
Injection site pruritus  1  1/17 (5.88%)  10/34 (29.41%) 
Injection site rash  1  0/17 (0.00%)  2/34 (5.88%) 
Injection site recall reaction  1  0/17 (0.00%)  1/34 (2.94%) 
Injection site swelling  1  0/17 (0.00%)  4/34 (11.76%) 
Injection site warmth  1  0/17 (0.00%)  1/34 (2.94%) 
Oedema peripheral  1  0/17 (0.00%)  1/34 (2.94%) 
Pyrexia  1  1/17 (5.88%)  3/34 (8.82%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  0/17 (0.00%)  1/34 (2.94%) 
Infections and infestations     
Cystitis  1  1/17 (5.88%)  0/34 (0.00%) 
Ear infection  1  0/17 (0.00%)  1/34 (2.94%) 
Fungal infection  1  1/17 (5.88%)  0/34 (0.00%) 
Gastroenteritis  1  0/17 (0.00%)  1/34 (2.94%) 
Influenza  1  2/17 (11.76%)  2/34 (5.88%) 
Nasopharyngitis  1  1/17 (5.88%)  0/34 (0.00%) 
Rhinitis  1  0/17 (0.00%)  1/34 (2.94%) 
Tooth abscess  1  1/17 (5.88%)  0/34 (0.00%) 
Upper respiratory tract infection  1  4/17 (23.53%)  1/34 (2.94%) 
Urinary tract infection  1  2/17 (11.76%)  0/34 (0.00%) 
Injury, poisoning and procedural complications     
Head injury  1  1/17 (5.88%)  0/34 (0.00%) 
Procedural pain  1  0/17 (0.00%)  1/34 (2.94%) 
Investigations     
Alanine aminotransferase increased  1  0/17 (0.00%)  5/34 (14.71%) 
Aspartate aminotransferase increased  1  1/17 (5.88%)  4/34 (11.76%) 
Blood creatine phosphokinase increased  1  0/17 (0.00%)  1/34 (2.94%) 
Hepatic enzyme increased  1  1/17 (5.88%)  0/34 (0.00%) 
Protein urine present  1  1/17 (5.88%)  0/34 (0.00%) 
Red blood cell macrocytes present  1  1/17 (5.88%)  0/34 (0.00%) 
Metabolism and nutrition disorders     
Anorexia  1  2/17 (11.76%)  0/34 (0.00%) 
Hyperglycaemia  1  0/17 (0.00%)  1/34 (2.94%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/17 (5.88%)  0/34 (0.00%) 
Back pain  1  0/17 (0.00%)  1/34 (2.94%) 
Intervertebral disc protrusion  1  1/17 (5.88%)  0/34 (0.00%) 
Musculoskeletal pain  1  0/17 (0.00%)  1/34 (2.94%) 
Pain in extremity  1  0/17 (0.00%)  2/34 (5.88%) 
Nervous system disorders     
Dizziness  1  0/17 (0.00%)  2/34 (5.88%) 
Facial palsy  1  0/17 (0.00%)  1/34 (2.94%) 
Headache  1  2/17 (11.76%)  5/34 (14.71%) 
Neuralgia  1  0/17 (0.00%)  1/34 (2.94%) 
Somnolence  1  0/17 (0.00%)  1/34 (2.94%) 
Psychiatric disorders     
Anxiety  1  0/17 (0.00%)  1/34 (2.94%) 
Stress  1  0/17 (0.00%)  1/34 (2.94%) 
Renal and urinary disorders     
Proteinuria  1  0/17 (0.00%)  1/34 (2.94%) 
Reproductive system and breast disorders     
Amenorrhoea  1  0/17 (0.00%)  1/34 (2.94%) 
Galactorrhoea  1  0/17 (0.00%)  1/34 (2.94%) 
Menorrhagia  1  1/17 (5.88%)  1/34 (2.94%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/17 (5.88%)  0/34 (0.00%) 
Cough  1  1/17 (5.88%)  0/34 (0.00%) 
Epistaxis  1  1/17 (5.88%)  0/34 (0.00%) 
Oropharyngeal pain  1  1/17 (5.88%)  0/34 (0.00%) 
Painful respiration  1  0/17 (0.00%)  1/34 (2.94%) 
Productive cough  1  0/17 (0.00%)  1/34 (2.94%) 
Upper respiratory tract congestion  1  0/17 (0.00%)  1/34 (2.94%) 
Skin and subcutaneous tissue disorders     
Dermatitis allergic  1  0/17 (0.00%)  1/34 (2.94%) 
Dry skin  1  1/17 (5.88%)  0/34 (0.00%) 
Eczema  1  1/17 (5.88%)  0/34 (0.00%) 
Pruritus generalised  1  1/17 (5.88%)  0/34 (0.00%) 
Rash  1  0/17 (0.00%)  1/34 (2.94%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
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.
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.
Results Point of Contact
Name/Title: Genzyme Medical Information
Organization: Genzyme Corporation
Phone: 617-252-7832
Responsible Party: Kastle Therapeutics, LLC
ClinicalTrials.gov Identifier: NCT00607373     History of Changes
Other Study ID Numbers: 301012CS5
2005-003449-15 ( EudraCT Number )
First Submitted: January 22, 2008
First Posted: February 5, 2008
Results First Submitted: February 15, 2013
Results First Posted: March 21, 2013
Last Update Posted: September 9, 2016