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| ID | Type | Description | Link |
|---|---|---|---|
| 2005-003449-15 | EudraCT Number |
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| Name | Class |
|---|---|
| Ionis Pharmaceuticals, Inc. | INDUSTRY |
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The purpose of this study is to evaluate the safety and efficacy of mipomersen (ISIS 301012) in subjects with homozygous familial hypercholesterolemia on lipid-lowering therapy.
This study consisted of a 26-week treatment period and a 24-week post-treatment follow-up period. Following treatment and Week 28 evaluations, participants could elect to enroll in an open-label extension study (301012-CS6; NCT00694109). Participants who were not eligible or elected not to enroll in the open-label extension study or who discontinued during the 28-week treatment period were followed in this study for 24 weeks from administration of the last dose of study drug.
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipoprotein metabolism characterized by markedly elevated low density lipoprotein (LDL), premature onset of atherosclerosis and development of xanthomata. Patients with homozygous familial hypercholesterolemia (HoFH) have a severe disease that presents in childhood with total cholesterol typically in the 650 to 1000 mg/dL range.
This was a randomized, double-blind, placebo-controlled study, which consisted of a 4-week screening period, 26 weeks of treatment, and a 24-week post- treatment follow-up period (with the exception of patients who enrolled in the open-label extension study, Study 301012-CS6; NCT00694109). Eligible patients were randomized in a 2:1 ratio to receive 200 mg mipomersen or matching volume placebo subcutaneous (SC) injections weekly. Patients who weighed <50 kg received a lower dose of 160 mg mipomersen or matching volume of placebo SC injections weekly. Patients were to have been on a stable (>=12 weeks) regimen of allowed lipid-lowering therapies at screening, and were required to remain on the same dose and regimen throughout the study.
Patients returned to the study center for clinical evaluation every other week during the first 4 weeks of treatment, once every 4 to 5 weeks for the remainder of the treatment period, and monthly during the post-treatment evaluation (follow-up) period. The primary endpoint assessment was at Week 28. Following treatment and Week 28 evaluations, eligible patients who tolerated the study drug could elect to enroll in the open-label extension study (Study 301012-CS6; NCT00694109). Patients who did not participate in the open-label extension study were required to return to the study center for clinical evaluation at least twice during the post-treatment follow-up period, including an end-of-study termination visit at the end of this 24-week period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mipomersen | Experimental | Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. |
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| Placebo | Placebo Comparator | Participants received placebo as a subcutaneous injection once a week for 26 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mipomersen | Drug | 200 mg mipomersen administered once a week for 26 weeks as a 1 mL subcutaneous injection. Subjects weighing less than 50 kg received a lower dose of 160 mg (0.8mL) mipomersen. |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point | 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. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| LDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET) | 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Genzyme, a Sanofi Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charlotte | North Carolina | 28204 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27578134 | Derived | Duell PB, Santos RD, Kirwan BA, Witztum JL, Tsimikas S, Kastelein JJP. Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia. J Clin Lipidol. 2016 Jul-Aug;10(4):1011-1021. doi: 10.1016/j.jacl.2016.04.013. Epub 2016 May 9. | |
| 25614280 | Derived |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received placebo as a subcutaneous injection once a week for 26 weeks |
| FG001 | Mipomersen | Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period |
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| Placebo | Drug | 1 mL subcutaneous injection once a week for 26 weeks. Subjects weighing less than 50 kg received 0.8 mL subcutaneous injection. |
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| Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Apo-B at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ) |
| Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET) | 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. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET) | 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. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Triglycerides at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET) | 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. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET) | 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. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| VLDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| 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) | 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. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET) | 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. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) | 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. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| HDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
| Cincinnati |
| Ohio |
| 45212 |
| United States |
| São Paulo | São Paulo | 05403-000 | Brazil |
| Chicoutimi | Quebec | G7H 5H6 | Canada |
| Ste Foy | Quebec | G1V 4G2 | Canada |
| Mistri Wing | 168752 | Singapore |
| Observatory | 7925 | South Africa |
| Parktown | 2193 | South Africa |
| Taipei | 11217 | Taiwan |
| London | WC1N 3BG | United Kingdom |
| Santos RD, Raal FJ, Catapano AL, Witztum JL, Steinhagen-Thiessen E, Tsimikas S. Mipomersen, an antisense oligonucleotide to apolipoprotein B-100, reduces lipoprotein(a) in various populations with hypercholesterolemia: results of 4 phase III trials. Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):689-99. doi: 10.1161/ATVBAHA.114.304549. Epub 2015 Jan 22. |
| 20227758 | Derived | Raal FJ, Santos RD, Blom DJ, Marais AD, Charng MJ, Cromwell WC, Lachmann RH, Gaudet D, Tan JL, Chasan-Taber S, Tribble DL, Flaim JD, Crooke ST. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010 Mar 20;375(9719):998-1006. doi: 10.1016/S0140-6736(10)60284-X. |
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| NOT COMPLETED |
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| Follow-up Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received placebo as a subcutaneous injection once a week for 26 weeks |
| BG001 | Mipomersen | Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Body Mass Index | Mean | Standard Deviation | kg/m^2 |
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| Waist/hip ratio | Mean | Standard Deviation | ratio |
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| Metabolic syndrome | 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 | Number | participants |
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| Tobacco Use | Number | participants |
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| Alcohol Use | Number | participants |
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| Fasting serum insulin | Mean | Standard Deviation | microIU/mL |
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| Fasting hemoglobin A1c | Mean | Standard Deviation | percentage of total hemoglobin |
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| Weight | 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. | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Primary Efficacy Time Point | 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. | 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. | Posted | Mean | Standard Deviation | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Secondary | Percent Change From Baseline in Apolipoprotein B (Apo-B) at Primary Efficacy Time Point | 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. | Full analysis set | Posted | Mean | Standard Deviation | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Secondary | Apo-B at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Mean | Standard Deviation | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 ) |
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| Secondary | Percentage Change From Baseline in Total Cholesterol at Primary Efficacy Time Point (PET) | 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. | Full analysis set | Posted | Mean | Standard Deviation | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Secondary | Total Cholesterol at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Mean | Standard Deviation | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Primary | LDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Mean | Standard Deviation | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Secondary | Percentage Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Primary Efficacy Time Point (PET) | 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. | Full analysis set | Posted | Mean | Standard Deviation | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Secondary | Non-HDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Mean | Standard Deviation | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Percentage Change From Baseline in Triglycerides at Primary Efficacy Time Point (PET) | 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. | Full analysis set | Posted | Median | Inter-Quartile Range | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Triglycerides at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Median | Inter-Quartile Range | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Percentage Change From Baseline in Lipoprotein(a) at Primary Efficacy Time Point (PET) | 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. | Full analysis set | Posted | Mean | Standard Deviation | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Lipoprotein(a) at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Mean | Standard Deviation | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Percentage Change From Baseline in Very-Low-Density Lipoprotein Cholesterol (VLDL-C) at Primary Efficacy Time Point (PET) | 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. | Full analysis set | Posted | Median | Inter-Quartile Range | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | VLDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Median | Inter-Quartile Range | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | 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) | 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. | Full analysis set | Posted | Mean | Standard Deviation | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Ratio of LDL-C to HDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Mean | Standard Deviation | ratio | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Percent Change From Baseline in Apolipoprotein A1 (Apo-A1) at Primary Efficacy Time Point (PET) | 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. | Full analysis set | Posted | Mean | Standard Deviation | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Apo-A1 at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Mean | Standard Deviation | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | Percentage Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Primary Efficacy Time Point (PET) | 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. | Full analysis set | Posted | Median | Inter-Quartile Range | percentage of baseline | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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| Other Pre-specified | HDL-C at Baseline and the Primary Efficacy Time Point (PET) | The PET was the post-baseline visit, for which LDL-C was assessed, closest to 14 days after the last dose of study drug. | Full analysis set | Posted | Median | Inter-Quartile Range | mg/dL | Baseline (the average of the screening and Day 1 pre-treatment assessments) and the Primary Efficacy Time point (PET) up to week 28 |
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Day 1 to week 28. On-treatment AEs started on/after the first study drug dose and on/before the end of the treatment period. The treatment period was the time study drug was administered until the later of the PET or 14 days after last study drug dose.
The Safety Set includes all randomized patients who receive at least 1 injection of the study treatment. In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received placebo as a subcutaneous injection once a week for 26 weeks | 1 | 17 | 13 | 17 | ||
| EG001 | Mipomersen | Participants received mipomersen 200 mg as a subcutaneous injection once a week for 26 weeks. | 2 | 34 | 30 | 34 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute coronary syndrome | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Ankle fracture | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Aortic valve disease | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Cardiac discomfort | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site anaesthesia | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site discolouration | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site discomfort | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site haematoma | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site haemorrhage | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site induration | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site inflammation | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site irritation | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site macule | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site oedema | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site pallor | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site papule | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site paraesthesia | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site pruritus | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site rash | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site recall reaction | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Injection site warmth | General disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 11.1 | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Ear infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Fungal infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Tooth abscess | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 11.1 | Systematic Assessment |
| |
| Head injury | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 11.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 11.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 11.1 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 11.1 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 11.1 | Systematic Assessment |
| |
| Protein urine present | Investigations | MedDRA 11.1 | Systematic Assessment |
| |
| Red blood cell macrocytes present | Investigations | MedDRA 11.1 | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 11.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Facial palsy | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Neuralgia | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 11.1 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| Stress | Psychiatric disorders | MedDRA 11.1 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Amenorrhoea | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
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| Galactorrhoea | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Painful respiration | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Upper respiratory tract congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 11.1 | Systematic Assessment |
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| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 11.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Genzyme Medical Information | Genzyme Corporation | 617-252-7832 |
| ID | Term |
|---|---|
| D008052 | Lipid Metabolism, Inborn Errors |
| D006938 | Hyperlipoproteinemia Type II |
| D006949 | Hyperlipidemias |
| D008659 | Metabolic Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D007232 | Infant, Newborn, Diseases |
| D000013 | Congenital Abnormalities |
| D006937 | Hypercholesterolemia |
| D006951 | Hyperlipoproteinemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D000090542 | Homozygous Familial Hypercholesterolemia |
| ID | Term |
|---|---|
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C524142 | mipomersen |
Not provided
Not provided
Not provided
| Withdrawal by Subject |
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| Male |
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| Not Hispanic or Latino |
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| Asian |
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| Black |
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| Yes |
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| Non-current |
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| Never |
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| Non-current |
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| Never |
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| >=50 kg |
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