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| ID | Type | Description | Link |
|---|---|---|---|
| 2005-005783-90 | EudraCT Number |
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| Name | Class |
|---|---|
| Ionis Pharmaceuticals, Inc. | INDUSTRY |
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This study will assess what, if any, effect that ISIS 301012 (mipomersen) has on liver triglyceride content in multiple groups of subjects with varying degrees of risk for hepatic steatosis. In order to enroll subject groups with varying degrees of risk, the study has included multiple cohorts (Cohorts A-G). Additions and removal of cohorts has been accomplished with protocol amendments.
This was a randomized, double-blind, placebo-controlled study to measure the effect of treatment with mipomersen on liver triglyceride (TG) content in patients with varying degrees of hyperlipidemia and risk for hepatic steatosis.
The original study design included 4 cohorts (Cohorts A through D). Subsequent protocol amendments added 3 cohorts (Cohorts E, F, and G) to the study, truncated the enrollment of Cohort D, and eliminated Cohorts B and C. The study consisted of up to a 3-week screening period; a 4-week (Cohorts A and D), 13-week (Cohort E), or 52-week (Cohort G) treatment period; and a 20-week post-treatment follow-up period. Cohort F was an observational cohort, and therefore, was not treated with study drug. Patients in this cohort underwent a 15-week Magnetic resonance spectroscopy (MRS) and ultrasound evaluation period.
The study cohorts are:
Cohort A: Healthy volunteers with LDL-C <140 mg/dL (3.6 mmol/L), serum TG <200 mg/dL (2.3 mmol/L), hemoglobin A1c (HbA1c) <6.0%, and hepatic TG content <5% (as measured by MRS at screening). Patients were randomized to mipomersen 200 mg or placebo and treated for 4 weeks.
Cohorts B+C were eliminated in a protocol amendment prior to enrolling any patients and are not discussed further.
Cohort D: In an amendment to the protocol, Cohort D was closed to enrollment. One patient had already been enrolled in the study prior to the amendment. The patient enrolled in this cohort had impaired fasting glucose (defined as fasting blood glucose >6 mmol/L and <7 mmol/L) and mixed dyslipidemia (LDL-C <215 mg/dL [5.6 mmol/L] and serum TG >200 mg/dL [2.3 mmol/L]). The patient was treated with mipomersen 200 mg for 4 weeks.
Cohort E: Patients with uncomplicated heterozygous familial hypercholesterolemia (HeFH) (Alanine aminotransferase (ALT) ≤1.5 * upper limit of normal Upper limit of normal (ULN), no evidence of insulin resistance or metabolic syndrome, and hepatic TG content <5% by MRS at screening). Patients were to remain on their baseline statin ± ezetimibe regimen but were to wash out from other lipid-lowering agents (e.g., fenofibrate, non-dietary omega-3 fatty acids, and niacin) at least 8 weeks prior to the MRS at screening. Patients were randomized to either mipomersen 200 mg or placebo for 13 weeks.
Cohort F: Patients with familial hypobetalipoproteinemia (FHBL) (a documented APOB gene mutation that results in the expression of a truncated form of apo B). Patients in this cohort were evaluated by MRS, ultrasound, and laboratory tests; however, they were not treated with mipomersen or placebo.
Cohort G: Patients with well-controlled type 2 diabetes mellitus (HbA1c ≤8.0%), hypercholesterolemia (LDL-C >100 mg/dL (2.59 mmol/L), and normal serum TG levels (≤200 mg/dL [2.26 mmol/L]). Patients were to have been on a stable dose of antidiabetic and lipid-lowering medications >3 months prior to screening and were expected to remain stable for the duration of the study. Patients were randomized to either mipomersen 200 mg or placebo for 26 weeks, followed by 26 additional weeks of mipomersen 200 mg. Recruiting difficulties caused this cohort to close early.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: mipomersen | Experimental | Healthy volunteers treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
|
| Cohort A: placebo | Placebo Comparator | Healthy volunteers treated with 6 injections of placebo over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
|
| Cohort D: mipomersen | Experimental | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
|
| Cohort D: placebo | Placebo Comparator | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of placebo over the course of 4 weeks. Injections were given subcutaneously (sc) on days 1, 4, 8, 11, 15 and 22. |
|
| Cohort E: mipomersen | Experimental | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| mipomersen | Drug | 200 mg subcutaneous injections |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Liver Triglyceride (TG) Content As Measured by Magnetic Resonance Spectroscopy (MRS) | Localized proton MRS was used to quantify liver TG concentration. All MRS imaging of the liver was performed using the same 1.5T scanner. The instructions were to cover the entire liver (from just above the dome to just below the inferior tip) using a qualified imaging technique (Yokoo, 2009, Radiology). Liver fat quantification was performed by determining the liver fat fraction (%) derived from MRS using selected Regions of Interest (ROI). The analyst typically looked for the branching of the right portal vein and mapped slices from one scan to the next. There were typically 2 ROIs in the right lobe and 1 in the left lobe. Magnetic resonance spectroscopy imaging ROIs between different scans were selected using anatomical landmarks for both time points. | Baseline, Day 26, Day 99 |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline Apolipoprotein B | Samples were taken following an overnight fast. | Baseline |
| Percent Change in Apolipoprotein B From Baseline to Day 99 | Samples were taken following an overnight fast. |
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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 |
|---|---|---|---|---|---|---|
| Amsterdam | 1105 AZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20008831 | Result | Visser ME, Akdim F, Tribble DL, Nederveen AJ, Kwoh TJ, Kastelein JJ, Trip MD, Stroes ES. Effect of apolipoprotein-B synthesis inhibition on liver triglyceride content in patients with familial hypercholesterolemia. J Lipid Res. 2010 May;51(5):1057-62. doi: 10.1194/jlr.M002915. Epub 2009 Dec 14. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A: Mipomersen | Healthy volunteers treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. |
| FG001 | Cohort A: Placebo | Healthy volunteers treated with 6 injections of placebo over the course of 4 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treated Period |
|
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|
| Cohort E: placebo | Placebo Comparator | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly placebo injections for 13 weeks. |
|
| Cohort F: no intervention | No Intervention | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| Cohort G: mipomersen | Experimental | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
|
| Cohort G: placebo followed by mipomersen | Placebo Comparator | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
|
|
| Placebo | Drug | subcutaneous injections |
|
| Day 26 and Day 99 |
| Baseline Low-Density Lipoprotein Cholesterol | Samples were taken following overnight fast. | Baseline |
| Percent Change in Low-Density Lipoprotein Cholesterol From Baseline to Day 99 | Samples were taken following an overnight fast. | Day 26 and Day 99 |
| Baseline Total Cholesterol | Samples were taken following an overnight fast. | Baseline |
| Percent Change in Total Cholesterol From Baseline to Day 99 | Samples were taken following an overnight fast. | Day 26 and Day 99 |
| FG002 | Cohort D: Mipomersen | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. |
| FG003 | Cohort D: Placebo | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of placebo over the course of 4 weeks. |
| FG004 | Cohort E: Placebo | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly placebo injections for 13 weeks. |
| FG005 | Cohort E: Mipomersen | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| FG006 | Cohort F: no Study Intervention | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| FG007 | Cohort G: Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| FG008 | Cohort G: Placebo Followed by Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| 20 Week Safety Follow-up |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A: Mipomersen | Healthy volunteers treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. |
| BG001 | Cohort A: Placebo | Healthy volunteers treated with 6 injections of placebo over the course of 4 weeks. |
| BG002 | Cohort D: Mipomersen | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of mipomersen 200 mg over the course of 4 weeks. |
| BG003 | Cohort D: Placebo | Participants with impaired fasting glucose and mixed dyslipidemia who were treated with 6 injections of placebo over the course of 4 weeks. |
| BG004 | Cohort E: Placebo | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly placebo injections for 13 weeks. |
| BG005 | Cohort E: Mipomersen | Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| BG006 | Cohort F: no Study Intervention | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| BG007 | Cohort G: Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| BG008 | Cohort G: Placebo Followed by Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| BG009 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Gender | Number | participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Number | participants |
|
| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Liver Triglyceride (TG) Content As Measured by Magnetic Resonance Spectroscopy (MRS) | Localized proton MRS was used to quantify liver TG concentration. All MRS imaging of the liver was performed using the same 1.5T scanner. The instructions were to cover the entire liver (from just above the dome to just below the inferior tip) using a qualified imaging technique (Yokoo, 2009, Radiology). Liver fat quantification was performed by determining the liver fat fraction (%) derived from MRS using selected Regions of Interest (ROI). The analyst typically looked for the branching of the right portal vein and mapped slices from one scan to the next. There were typically 2 ROIs in the right lobe and 1 in the left lobe. Magnetic resonance spectroscopy imaging ROIs between different scans were selected using anatomical landmarks for both time points. | Full analysis set. In Cohort E: Placebo, Day 99 N=11 instead of 10 because participant did not have a post treatment MRS by Day 26. | Posted | Median | Full Range | percentage of total liver content | Baseline, Day 26, Day 99 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Baseline Apolipoprotein B | Samples were taken following an overnight fast. | Full analysis set | Posted | Median | Inter-Quartile Range | mg/wk | Baseline |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change in Apolipoprotein B From Baseline to Day 99 | Samples were taken following an overnight fast. | Full analysis set with last observation carried forward. | Posted | Median | Inter-Quartile Range | percent change | Day 26 and Day 99 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Baseline Low-Density Lipoprotein Cholesterol | Samples were taken following overnight fast. | Full analysis set | Posted | Median | Inter-Quartile Range | mg/wk | Baseline |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change in Low-Density Lipoprotein Cholesterol From Baseline to Day 99 | Samples were taken following an overnight fast. | Full analysis set with last observation carried forward. | Posted | Median | Inter-Quartile Range | percent change | Day 26 and Day 99 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Baseline Total Cholesterol | Samples were taken following an overnight fast. | Full analysis set | Posted | Median | Inter-Quartile Range | mg/wk | Baseline |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percent Change in Total Cholesterol From Baseline to Day 99 | Samples were taken following an overnight fast. | Full analysis set with last observation carried forward. | Posted | Median | Inter-Quartile Range | percent change | Day 26 and Day 99 |
|
Not provided
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo | 0 | 14 | 14 | 14 | ||
| EG001 | Mipomersen | Mipomersen | 1 | 19 | 19 | 19 | ||
| EG002 | Not Treated | Not Treated | 0 | 6 | 3 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasal septum disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Eosinophilia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Eustachian tube disorder | Ear and labyrinth disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Eye inflammation | Eye disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Irritable bowel syndrome | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Tooth disorder | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Feeling cold | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site discolouration | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site discomfort | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site haematoma | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site induration | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site inflammation | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site pallor | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site pruritus | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Hepatic fibrosis | Hepatobiliary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Hepatic pain | Hepatobiliary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Hepatic steatosis | Hepatobiliary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Liver disorder | Hepatobiliary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Allergy to arthropod bite | Immune system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Pertussis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
| |
| Joint injury | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
| |
| Post procedural complication | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
| |
| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Hepatic enzyme increased | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Protein urine present | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Urine analysis abnormal | Investigations | MedDRA 13.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Carotid artery stenosis | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Dizziness postural | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Head discomfort | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Affect lability | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Listless | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Microalbuminuria | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Urine abnormality | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Prostatomegaly | Reproductive system and breast disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Diaphragmatic disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Nasal septum disorder | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Increased tendency to bruise | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 13.0 | Systematic Assessment |
| |
| Subclavian artery stenosis | Vascular disorders | MedDRA 13.0 | Systematic Assessment |
|
The limitations to this study are 1) post-hoc amendments that caused early termination of cohorts and limited the accomplishment of study objectives and 2) post-hoc amendments which added cohorts into the study that were not previously specified.
PI gives Sponsor a draft 90 days before publication. Sponsor has the right to demand that confidential information be removed, and can defer publication another 180 days upon notifying PI that it will file a patent application on inventions contained in the draft.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christopher Bryant, Ph.D. | Kastle Therapeutics, LLC | 8152633913 | cbryant@kastletx.com |
| ID | Term |
|---|---|
| D008052 | Lipid Metabolism, Inborn Errors |
| D006949 | Hyperlipidemias |
| D008659 | Metabolic Diseases |
| D007009 | Hypolipoproteinemias |
| D006995 | Hypobetalipoproteinemias |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D007232 | Infant, Newborn, Diseases |
| D000013 | Congenital Abnormalities |
| D006937 | Hypercholesterolemia |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| 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
| Male |
|
| Black or African American |
|
Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks.
| Day 26 (Cohort E: Placebo n=10) |
|
| Day 99 (Cohort E: Placebo n=11) |
|
| exact Wilcoxon Rank-sum test |
| 0.0513 |
| 2-Sided |
| No |
| Superiority or Other |
Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| OG005 | Cohort F: no Study Intervention | Participants with a diagnosis of Familial Hypobetalipoproteinemia (FHBL) and were not treated with mipomersen or placebo. |
| OG006 | Cohort G: Placebo Followed by Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| OG007 | Cohort G: Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
|
|
| Cohort E: Mipomersen |
Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| OG005 | Cohort F: No Study Intervention | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| OG006 | Cohort G: Placebo Followed by Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| OG007 | Cohort G: Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
|
|
Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| OG005 | Cohort F: No Study Intervention | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| OG006 | Cohort G: Placebo Followed by Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| OG007 | Cohort G: Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
|
|
| OG004 |
| Cohort E: Mipomersen |
Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| OG005 | Cohort F: No Study Intervention | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| OG006 | Cohort G: Placebo Follwed by Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| OG007 | Cohort G: Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
|
|
Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly mipomersen 200 mg injections for 13 weeks. |
| OG005 | Cohort F: No Study Intervention | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| OG006 | Cohort G: Placebo Followed by Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| OG007 | Cohort G: Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
|
|
| OG004 |
| Cohort E: Placebo |
Participants with uncomplicated heterozygous familial hypercholesterolemia (HeFH) treated with weekly placebo injections for 13 weeks. |
| OG005 | Cohort F: No Study Intervention | A reference group of participants with familial hypobetalipoproteinemia (FBHL) who did not receive a study intervention. Data gathered for 15 weeks. |
| OG006 | Cohort G: Placebo Follwed by Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with placebo weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
| OG007 | Cohort G: Mipomersen | Participants with well-controlled Type 2 diabetes mellitus, hypercholesterolemia, and normal triglyceride levels were treated with mipomersen 200 mg weekly for 26 weeks, followed by open-label mipomersen 200 mg weekly for an additional 26 weeks. |
|
|