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Trial record 14 of 19 for:    MIPOMERSEN

Safety and Efficacy Study of ISIS 301012 (Mipomersen) Administration in High Risk Statin Intolerant Subjects (ASSIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00707746
Recruitment Status : Completed
First Posted : July 1, 2008
Results First Posted : April 5, 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 Metabolic Diseases
Hyperlipidemias
Metabolic Disorder
Hypercholesterolemia
Dyslipidemias
Lipid Metabolism Disorders
Interventions Drug: mipomersen
Drug: placebo
Enrollment 34
Recruitment Details  
Pre-assignment Details 42 patients were screened, 34 participants were randomized, and 33 participants were treated: 21 participants to mipomersen and 12 participants to placebo.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description 1 mL placebo saline, weekly subcutaneous injections for 26 weeks 200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Period Title: Treatment Period
Started 12 22
Full Analysis Set (FAS) and Safety Set 12 [1] 21 [1]
Completed 10 17
Not Completed 2 5
Reason Not Completed
Adverse Event             2             4
Ineligibility             0             1
[1]
FAS: Treated patients with a valid baseline & post-baseline LDL-C measurement
Period Title: Follow-up Period
Started 12 21
Completed 12 21
Not Completed 0 0
Arm/Group Title Placebo Mipomersen Total
Hide Arm/Group Description 1 mL placebo saline, weekly subcutaneous injections for 26 weeks 200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks Total of all reporting groups
Overall Number of Baseline Participants 12 21 33
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 21 participants 33 participants
51.7  (8.7) 55.6  (6.8) 54.2  (7.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 21 participants 33 participants
Female
8
  66.7%
10
  47.6%
18
  54.5%
Male
4
  33.3%
11
  52.4%
15
  45.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 21 participants 33 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
12
 100.0%
21
 100.0%
33
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 21 participants 33 participants
White 12 20 32
Black 0 1 1
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 12 participants 21 participants 33 participants
26.06  (2.49) 26.46  (3.25) 26.31  (2.96)
Waist/hip Ratio  
Mean (Standard Deviation)
Unit of measure:  Ratio
Number Analyzed 12 participants 21 participants 33 participants
0.92  (0.09) 0.93  (0.08) 0.93  (0.08)
Metabolic syndrome   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 21 participants 33 participants
No 4 12 16
Yes 8 9 17
[1]
Measure Description:

A participant was classified as having metabolic syndrome if any 3 of the following risk factors existed: 1) Waist circumference ≥102 cm (men) or ≥88 cm (women); 2) Triglycerides ≥150 mg/dl *; 3) High density lipoprotein cholesterol <40 mg/dl (men) or <50 mg/dl (women)*; 4) Systolic blood pressure ≥130 or diastolic ≥85 mmHg *; 5) Fasting glucose ≥100 mg/dl *.

* = or on medication for the specified risk factor.

Tobacco Use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 21 participants 33 participants
Current 2 6 8
Non-current 5 9 14
Never 5 6 11
Alcohol use  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 21 participants 33 participants
Current 8 16 24
Non-current 2 3 5
Never 2 2 4
1.Primary Outcome
Title Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at the 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. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-2.0  (8.40) -47.3  (18.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Mipomersen
Comments It was estimated that the standard deviation of the percent change in LDL-C was 20%. A sample size of 30 patients was planned for this study: 20 patients in the mipomersen group and 10 patients in the placebo group. A 2-sided t-test with an alpha level of 0.05 was expected to provide ≥90% power to detect a 30% difference in LDL-C percent reduction between the 2 groups (35% reduction for the mipomersen group and 5% reduction for the placebo group).
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 Low-density Lipoprotein Cholesterol at Baseline and the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 243.7  (65.6) 241.9  (90.8)
Primary efficacy time point 236.3  (52.8) 128.3  (74.2)
3.Primary Outcome
Title Summary of Participants With Adverse Events
Hide Description

The on-treatment time frame spanned the time during which the study drug was administered until the later of the primary efficacy time point and 14 days beyond the last study drug date.

Adverse events (AEs) were considered related if assessed by the Investigator as possibly, probably or definitely related to study drug.

Severity was assessed as:

  • Mild-symptom barely noticeable to the patient or do not make the patient uncomfortable;
  • Moderate-symptom makes the patient uncomfortable, affects performance of daily activities;
  • Severe-symptom causes the patient severe discomfort, may cause cessation of treatment with the study drug.

Serious AEs (SAEs) are those that resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in an important medical event that may have jeopardized the patient or required medical or surgical intervention.

Time Frame Pre-treatment (prior to first dose), On-treatment (Day 1 to week 28), Post-treatment (Week 28-52)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set of all randomized participants who received at least one injection of study drug.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Measure Type: Number
Unit of Measure: participants
Pre-treatment adverse events (AEs) 3 7
Post-treatment AEs 9 20
On-treatment AEs 12 21
On-treatment AEs-related 12 21
On-treatment AEs-mild 6 5
On-treatment AEs-moderate 5 16
On-treatment AEs-severe 1 0
On-treatment AEs-leading to trt discontinuation 2 4
On-treatment Serious Adverse Events (SAEs) 1 0
On-treatment SAEs-related 1 0
On-treatment SAEs-mild 0 0
On-treatment SAEs-moderate 0 0
On-treatment SAEs-severe 1 0
On-treatment SAEs-leading to trt discontinuation 1 0
Deaths 0 0
4.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B at the Primary Efficacy Time Point
Hide Description Apolipoprotein B was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Median (Inter-Quartile Range)
Unit of Measure: percentage of baseline
-4.0
(-8.8 to 0.5)
-45.8
(-57.5 to -34.4)
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 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 Wilcoxon signed rank sum
Comments [Not Specified]
5.Secondary Outcome
Title Apolipoprotein B at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Median (Inter-Quartile Range)
Unit of Measure: mg/dL
Baseline
180
(145 to 196)
177
(142 to 205)
Primary efficacy time point
173
(143 to 187)
96
(66 to 110)
6.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol at the Primary Efficacy Time Point
Hide Description Total cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-1.7  (6.46) -36.9  (14.66)
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]
7.Secondary Outcome
Title Total Cholesterol at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 322.3  (66.2) 318.9  (91.8)
Primary efficacy time point 314.5  (53.0) 200.1  (77.6)
8.Secondary Outcome
Title Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point
Hide Description Non-high-density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-1.9  (7.06) -45.6  (18.22)
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]
9.Secondary Outcome
Title Non-High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 273.5  (65.3) 270.1  (92.9)
Primary efficacy time point 266.0  (53.0) 147.7  (81.1)
10.Other Pre-specified Outcome
Title Percent Change From Baseline in Triglycerides at the Primary Efficacy Time Point
Hide Description Triglycerides were measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
5.0  (26.81) -27.0  (30.21)
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 0.005
Comments Statistical significance was concluded if p ≤0.05. No further adjustments were made for tertiary parameters.
Method t-test, 2 sided
Comments [Not Specified]
11.Other Pre-specified Outcome
Title Triglycerides at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 149.0  (63.9) 141.4  (50.9)
Primary efficacy time point 149.3  (62.4) 97.3  (47.3)
12.Other Pre-specified Outcome
Title Percent Change From Baseline in Lipoprotein (a) at the Primary Efficacy Time Point
Hide Description Lipoprotein (a) was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
0.0  (8.65) -27.1  (31.19)
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. No further adjustments were made for tertiary parameters.
Method t-test, 2 sided
Comments [Not Specified]
13.Other Pre-specified Outcome
Title Lipoprotein (a) at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 37.3  (76.3) 53.5  (45.8)
Primary efficacy time point 41.3  (90.1) 42.3  (48.2)
14.Other Pre-specified Outcome
Title Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol at the Primary Efficacy Time Point
Hide Description Very low density lipoprotein cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
4.6  (26.53) -27.1  (30.79)
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 0.006
Comments Statistical significance was concluded if p ≤0.05. No further adjustments were made for tertiary parameters.
Method t-test, 2 sided
Comments [Not Specified]
15.Other Pre-specified Outcome
Title Very Low Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 29.8  (12.7) 28.3  (10.2)
Primary efficacy time point 29.8  (12.5) 19.4  (9.5)
16.Other Pre-specified Outcome
Title Percent Change From Baseline in the Ratio of Low-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point
Hide Description The ratio of low-density lipoprotein (LDL) cholesterol to high-density lipoprotein (HDL) cholesterol was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
1.4  (12.84) -49.2  (22.16)
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. No further adjustments were made for tertiary parameters.
Method t-test, 2 sided
Comments [Not Specified]
17.Other Pre-specified Outcome
Title Ratio of Low-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: ratio
Baseline 5.3  (2.18) 5.2  (2.38)
Primary efficacy time point 5.4  (2.27) 2.7  (2.21)
18.Other Pre-specified Outcome
Title Percent Change From Baseline in Apolipoprotein A1 at the Primary Efficacy Time Point
Hide Description Apolipoprotein A1 was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-1.2  (11.11) -0.0  (12.45)
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 0.784
Comments Statistical significance was concluded if p ≤0.05. No further adjustments were made for tertiary parameters.
Method t-test, 2 sided
Comments [Not Specified]
19.Other Pre-specified Outcome
Title Apolipoprotein A1 at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 150.0  (24.8) 150.3  (25.6)
Primary efficacy time point 148.9  (33.2) 149.1  (24.0)
20.Other Pre-specified Outcome
Title Percent Change From Baseline in High-Density Lipoprotein Cholesterol at the Primary Efficacy Time Point
Hide Description High-density lipoprotein cholesterol (HDL-C) was measured in mg/dL. Samples were taken following an overnight fast. The primary efficacy time point was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
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Hide Analysis Population Description
The Full Analysis Set, which consisted of all randomized patients who received at least 1 injection of study drug (mipomersen or placebo) and with a valid baseline and at least 1 post-baseline LDL-C measurement.
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: percentage of baseline
-2.3  (12.72) 8.1  (17.15)
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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 0.079
Comments Statistical significance was concluded if p ≤0.05. No further adjustments were made for tertiary parameters.
Method t-test, 2 sided
Comments [Not Specified]
21.Other Pre-specified Outcome
Title High-Density Lipoprotein Cholesterol at Baseline and at the Primary Efficacy Time Point
Hide Description The primary efficacy time point (PET) was the post-baseline visit closest to 14 days after the last dose of study treatment.
Time Frame Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET; Week 28 or the post-baseline visit closest to 14 days after the last dose).
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Mipomersen
Hide Arm/Group Description:
1 mL placebo saline, weekly subcutaneous injections for 26 weeks
200 mg (1 mL) of mipomersen, weekly subcutaneous injections for 26 weeks
Overall Number of Participants Analyzed 12 21
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline 48.8  (12.4) 48.8  (9.9)
Primary efficacy time point 48.5  (16.9) 52.4  (12.4)
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 1 mL placebo saline, weekly subcutaneous injections for 26 weeks 200 mg (1 mL) of mipomersen, 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   1/12 (8.33%)   0/21 (0.00%) 
Cardiac disorders     
Acute myocardial infarction  1  1/12 (8.33%)  0/21 (0.00%) 
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   12/12 (100.00%)   21/21 (100.00%) 
Blood and lymphatic system disorders     
Haemorrhagic diathesis  1  0/12 (0.00%)  1/21 (4.76%) 
Cardiac disorders     
Angina pectoris  1  1/12 (8.33%)  0/21 (0.00%) 
Left ventricular hypertrophy  1  0/12 (0.00%)  1/21 (4.76%) 
Palpitations  1  0/12 (0.00%)  2/21 (9.52%) 
Ear and labyrinth disorders     
Deafness unilateral  1  1/12 (8.33%)  0/21 (0.00%) 
Eye disorders     
Eye allergy  1  0/12 (0.00%)  1/21 (4.76%) 
Eye inflammation  1  0/12 (0.00%)  1/21 (4.76%) 
Eye pruritus  1  0/12 (0.00%)  1/21 (4.76%) 
Panophthalmitis  1  0/12 (0.00%)  1/21 (4.76%) 
Gastrointestinal disorders     
Abdominal discomfort  1  1/12 (8.33%)  0/21 (0.00%) 
Abdominal distension  1  1/12 (8.33%)  0/21 (0.00%) 
Abdominal pain  1  1/12 (8.33%)  3/21 (14.29%) 
Abdominal pain lower  1  1/12 (8.33%)  1/21 (4.76%) 
Abdominal pain upper  1  1/12 (8.33%)  4/21 (19.05%) 
Abnormal faeces  1  0/12 (0.00%)  1/21 (4.76%) 
Change of bowel habit  1  1/12 (8.33%)  0/21 (0.00%) 
Constipation  1  1/12 (8.33%)  1/21 (4.76%) 
Diarrhoea  1  3/12 (25.00%)  8/21 (38.10%) 
Dyspepsia  1  1/12 (8.33%)  1/21 (4.76%) 
Faeces discoloured  1  0/12 (0.00%)  2/21 (9.52%) 
Faeces hard  1  1/12 (8.33%)  0/21 (0.00%) 
Flatulence  1  0/12 (0.00%)  2/21 (9.52%) 
Food poisoning  1  0/12 (0.00%)  1/21 (4.76%) 
Frequent bowel movements  1  1/12 (8.33%)  0/21 (0.00%) 
Gastrointestinal pain  1  2/12 (16.67%)  0/21 (0.00%) 
Gingivitis  1  0/12 (0.00%)  1/21 (4.76%) 
Haemorrhoids  1  0/12 (0.00%)  2/21 (9.52%) 
Intestinal functional disorder  1  0/12 (0.00%)  1/21 (4.76%) 
Nausea  1  4/12 (33.33%)  6/21 (28.57%) 
Tooth disorder  1  1/12 (8.33%)  2/21 (9.52%) 
Toothache  1  0/12 (0.00%)  1/21 (4.76%) 
Vomiting  1  0/12 (0.00%)  1/21 (4.76%) 
General disorders     
Asthenia  1  1/12 (8.33%)  2/21 (9.52%) 
Chest discomfort  1  0/12 (0.00%)  1/21 (4.76%) 
Chest pain  1  0/12 (0.00%)  1/21 (4.76%) 
Fatigue  1  2/12 (16.67%)  8/21 (38.10%) 
Feeling abnormal  1  1/12 (8.33%)  1/21 (4.76%) 
Feeling cold  1  0/12 (0.00%)  1/21 (4.76%) 
Impaired healing  1  0/12 (0.00%)  1/21 (4.76%) 
Influenza like illness  1  6/12 (50.00%)  10/21 (47.62%) 
Injection site discolouration  1  0/12 (0.00%)  13/21 (61.90%) 
Injection site discomfort  1  1/12 (8.33%)  6/21 (28.57%) 
Injection site erythema  1  0/12 (0.00%)  18/21 (85.71%) 
Injection site exfoliation  1  0/12 (0.00%)  1/21 (4.76%) 
Injection site haematoma  1  7/12 (58.33%)  12/21 (57.14%) 
Injection site induration  1  1/12 (8.33%)  11/21 (52.38%) 
Injection site inflammation  1  0/12 (0.00%)  4/21 (19.05%) 
Injection site nodule  1  0/12 (0.00%)  3/21 (14.29%) 
Injection site pain  1  2/12 (16.67%)  14/21 (66.67%) 
Injection site pallor  1  0/12 (0.00%)  1/21 (4.76%) 
Injection site pruritus  1  0/12 (0.00%)  10/21 (47.62%) 
Injection site reaction  1  0/12 (0.00%)  2/21 (9.52%) 
Injection site swelling  1  0/12 (0.00%)  9/21 (42.86%) 
Injection site vesicles  1  0/12 (0.00%)  1/21 (4.76%) 
Injection site warmth  1  0/12 (0.00%)  1/21 (4.76%) 
Malaise  1  0/12 (0.00%)  2/21 (9.52%) 
Non-cardiac chest pain  1  1/12 (8.33%)  0/21 (0.00%) 
Pyrexia  1  0/12 (0.00%)  2/21 (9.52%) 
Sensation of pressure  1  1/12 (8.33%)  0/21 (0.00%) 
Tenderness  1  0/12 (0.00%)  1/21 (4.76%) 
Vessel puncture site haematoma  1  0/12 (0.00%)  2/21 (9.52%) 
Vessel puncture site reaction  1  0/12 (0.00%)  1/21 (4.76%) 
Hepatobiliary disorders     
Hepatic steatosis  1  1/12 (8.33%)  11/21 (52.38%) 
Infections and infestations     
Eye infection  1  0/12 (0.00%)  1/21 (4.76%) 
Herpes zoster  1  0/12 (0.00%)  1/21 (4.76%) 
Influenza  1  3/12 (25.00%)  1/21 (4.76%) 
Injection site cellulitis  1  0/12 (0.00%)  1/21 (4.76%) 
Nasopharyngitis  1  4/12 (33.33%)  8/21 (38.10%) 
Oral herpes  1  0/12 (0.00%)  1/21 (4.76%) 
Sinusitis  1  1/12 (8.33%)  1/21 (4.76%) 
Urinary tract infection  1  0/12 (0.00%)  3/21 (14.29%) 
Injury, poisoning and procedural complications     
Contusion  1  1/12 (8.33%)  0/21 (0.00%) 
Fall  1  0/12 (0.00%)  1/21 (4.76%) 
Limb injury  1  1/12 (8.33%)  0/21 (0.00%) 
Post procedural complication  1  0/12 (0.00%)  1/21 (4.76%) 
Procedural pain  1  0/12 (0.00%)  1/21 (4.76%) 
Investigations     
Activated partial thromboplastin time  1  0/12 (0.00%)  1/21 (4.76%) 
Activated partial thromboplastin time prolonged  1  2/12 (16.67%)  1/21 (4.76%) 
Alanine aminotransferase increased  1  0/12 (0.00%)  6/21 (28.57%) 
Albumin urine present  1  0/12 (0.00%)  1/21 (4.76%) 
Aspartate aminotransferase increased  1  0/12 (0.00%)  6/21 (28.57%) 
Blood alkaline phosphatase increased  1  0/12 (0.00%)  1/21 (4.76%) 
Blood calcium decreased  1  0/12 (0.00%)  1/21 (4.76%) 
Blood phosphorus decreased  1  1/12 (8.33%)  2/21 (9.52%) 
Blood potassium increased  1  1/12 (8.33%)  0/21 (0.00%) 
Body temperature decreased  1  0/12 (0.00%)  3/21 (14.29%) 
Body temperature increased  1  0/12 (0.00%)  1/21 (4.76%) 
C-reactive protein increased  1  1/12 (8.33%)  1/21 (4.76%) 
Coagulation test abnormal  1  0/12 (0.00%)  1/21 (4.76%) 
Electrocardiogram poor R-wave progression  1  0/12 (0.00%)  1/21 (4.76%) 
Gastric pH decreased  1  0/12 (0.00%)  1/21 (4.76%) 
Globulins decreased  1  0/12 (0.00%)  1/21 (4.76%) 
Hepatic enzyme increased  1  0/12 (0.00%)  1/21 (4.76%) 
International normalised ratio increased  1  0/12 (0.00%)  1/21 (4.76%) 
Liver function test abnormal  1  0/12 (0.00%)  1/21 (4.76%) 
Platelet count decreased  1  0/12 (0.00%)  1/21 (4.76%) 
Protein urine present  1  0/12 (0.00%)  1/21 (4.76%) 
Prothrombin time prolonged  1  0/12 (0.00%)  1/21 (4.76%) 
Sputum abnormal  1  0/12 (0.00%)  1/21 (4.76%) 
Urine albumin/creatinine ratio increased  1  1/12 (8.33%)  4/21 (19.05%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/12 (0.00%)  2/21 (9.52%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/12 (8.33%)  1/21 (4.76%) 
Back pain  1  3/12 (25.00%)  5/21 (23.81%) 
Bone disorder  1  0/12 (0.00%)  1/21 (4.76%) 
Bursitis  1  1/12 (8.33%)  0/21 (0.00%) 
Groin pain  1  0/12 (0.00%)  2/21 (9.52%) 
Muscle spasms  1  4/12 (33.33%)  3/21 (14.29%) 
Musculoskeletal disorder  1  0/12 (0.00%)  1/21 (4.76%) 
Musculoskeletal pain  1  0/12 (0.00%)  2/21 (9.52%) 
Musculoskeletal stiffness  1  1/12 (8.33%)  2/21 (9.52%) 
Myalgia  1  5/12 (41.67%)  9/21 (42.86%) 
Myosclerosis  1  0/12 (0.00%)  1/21 (4.76%) 
Pain in extremity  1  1/12 (8.33%)  4/21 (19.05%) 
Pain in jaw  1  0/12 (0.00%)  1/21 (4.76%) 
Sensation of heaviness  1  1/12 (8.33%)  1/21 (4.76%) 
Tendon pain  1  3/12 (25.00%)  0/21 (0.00%) 
Nervous system disorders     
Aphonia  1  0/12 (0.00%)  1/21 (4.76%) 
Dizziness  1  3/12 (25.00%)  3/21 (14.29%) 
Dizziness postural  1  0/12 (0.00%)  1/21 (4.76%) 
Headache  1  3/12 (25.00%)  9/21 (42.86%) 
Migraine with aura  1  0/12 (0.00%)  1/21 (4.76%) 
Paraesthesia  1  2/12 (16.67%)  2/21 (9.52%) 
Poor quality sleep  1  1/12 (8.33%)  0/21 (0.00%) 
Syncope  1  1/12 (8.33%)  0/21 (0.00%) 
Psychiatric disorders     
Depressed mood  1  0/12 (0.00%)  1/21 (4.76%) 
Initial insomnia  1  0/12 (0.00%)  1/21 (4.76%) 
Listless  1  0/12 (0.00%)  2/21 (9.52%) 
Tension  1  0/12 (0.00%)  2/21 (9.52%) 
Renal and urinary disorders     
Pollakiuria  1  0/12 (0.00%)  1/21 (4.76%) 
Proteinuria  1  0/12 (0.00%)  1/21 (4.76%) 
Reproductive system and breast disorders     
Menstruation irregular  1  1/12 (8.33%)  0/21 (0.00%) 
Postmenopausal haemorrhage  1  0/12 (0.00%)  1/21 (4.76%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  0/12 (0.00%)  1/21 (4.76%) 
Cough  1  2/12 (16.67%)  5/21 (23.81%) 
Epistaxis  1  1/12 (8.33%)  0/21 (0.00%) 
Oropharyngeal pain  1  2/12 (16.67%)  4/21 (19.05%) 
Rhinitis allergic  1  1/12 (8.33%)  0/21 (0.00%) 
Rhinorrhoea  1  0/12 (0.00%)  1/21 (4.76%) 
Skin and subcutaneous tissue disorders     
Eczema  1  1/12 (8.33%)  0/21 (0.00%) 
Hyperkeratosis  1  0/12 (0.00%)  1/21 (4.76%) 
Nail disorder  1  1/12 (8.33%)  0/21 (0.00%) 
Nail growth abnormal  1  1/12 (8.33%)  0/21 (0.00%) 
Pruritus generalised  1  0/12 (0.00%)  2/21 (9.52%) 
Rash  1  0/12 (0.00%)  1/21 (4.76%) 
Skin burning sensation  1  0/12 (0.00%)  1/21 (4.76%) 
Vascular disorders     
Haematoma  1  0/12 (0.00%)  1/21 (4.76%) 
Hot flush  1  0/12 (0.00%)  3/21 (14.29%) 
Hypertension  1  0/12 (0.00%)  2/21 (9.52%) 
Vasodilatation  1  1/12 (8.33%)  0/21 (0.00%) 
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.
Institution will submit for review a proposed publication or presentation at least 90 days prior to submission date. Sponsor has the right to delay publication or presentation for not more than 6 months to address patent applications. Sponsor also has the right to demand in writing the deletion of confidential information. Investigator will not make public raw study data, detailed subject cases, or information identifying any subject.
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: NCT00707746     History of Changes
Other Study ID Numbers: 301012-CS19
2007-005140-24 ( EudraCT Number )
First Submitted: June 27, 2008
First Posted: July 1, 2008
Results First Submitted: February 25, 2013
Results First Posted: April 5, 2013
Last Update Posted: September 9, 2016