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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1134-4749 | Other Identifier | UTN |
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| Name | Class |
|---|---|
| Regeneron Pharmaceuticals | INDUSTRY |
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Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9).
Primary Objective of the study:
To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥100 mg/dL (≥2.59 mmol/L) on ongoing stable atorvastatin therapy.
Secondary Objectives:
The duration of study participation depended on the status of the participant at screening: 21 to 27 weeks including a screening/run-in period of 1 to 7 weeks, a double-blind treatment period of 12 weeks, followed by an 8-week follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose. |
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| Alirocumab 50 mg Q2W | Experimental | Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
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| Alirocumab 75 mg Q2W | Experimental | Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
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| Alirocumab 150 mg Q2W | Placebo Comparator | Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alirocumab | Drug | Two SC injections in the abdomen only |
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| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational product (IP) injection up to 21 days after last IP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method. | Baseline to Week 12 (LOCF) |
| Measure | Description | Time Frame |
|---|---|---|
| Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | Baseline to Week 12 (LOCF) |
| Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis |
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Inclusion criteria :
- Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 5-20 mg for at least 6 weeks prior to screening and likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) at the screening visit.
OR
- Participants with primary hypercholesterolemia who were receiving a lipid-lowering treatment other than atorvastatin, or who were not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening if they were likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after a 6-week run-in treatment period on atorvastatin therapy.
Exclusion criteria:
LDL-C <100 mg/dL (<2.59 mmol/L)
Participants with type 1 diabetes
Participants with type 2 diabetes treated with insulin, or without, and considered poorly controlled at screening.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigational Site Number 392002 | Koganeishi | Japan | ||||
| Investigational Site Number 392001 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27184170 | Result | Teramoto T, Kobayashi M, Uno K, Takagi Y, Matsuoka O, Sugimoto M, Inoue S, Minami F, Baccara-Dinet MT. Efficacy and Safety of Alirocumab in Japanese Subjects (Phase 1 and 2 Studies). Am J Cardiol. 2016 Jul 1;118(1):56-63. doi: 10.1016/j.amjcard.2016.04.011. Epub 2016 Apr 21. | |
| 30183102 | Derived | Leiter LA, Tinahones FJ, Karalis DG, Bujas-Bobanovic M, Letierce A, Mandel J, Samuel R, Jones PH. Alirocumab safety in people with and without diabetes mellitus: pooled data from 14 ODYSSEY trials. Diabet Med. 2018 Dec;35(12):1742-1751. doi: 10.1111/dme.13817. Epub 2018 Oct 9. |
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Randomization was stratified according to atorvastatin dose. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1:1:1 ratio after confirmation of selection criteria. 100 participants were randomized.
The study was conducted at 4 centers in Japan. Overall, 162 participants were screened between March 2013 and August 2013, 62 of whom were run-in/screen failures, mainly due to exclusion criteria met.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo (for alirocumab) every 2 weeks (Q2W) for 12-weeks in combination with atorvastatin stable dose. |
| FG001 | Alirocumab 50 mg Q2W | Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo (for alirocumab) | Drug | Two subcutaneous (SC) injections in the abdomen only Route of administration: subcutaneous injection (1 mL) in the abdomen |
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| Atorvastatin | Drug | Orally once daily at a stable dose of 5 to 20 mg as background therapy Route of administration: oral administration in the evening |
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Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. |
| Baseline to Week 12 (LOCF) |
| Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | Week 12 (LOCF) |
| Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | Baseline to Week 12 (LOCF) |
| Percent Change From Baseline in Fasting Triglycerides and Lipoprotein (a) at Week 12 - On-Treatment Analysis | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range). | Baseline to Week 12 (LOCF) |
| Absolute Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis | Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint. | From Baseline to Week 12 (LOCF) |
| Shinjuku-Ku |
| Japan |
| Investigational Site Number 392003 | Suita-Shi | Japan |
| Investigational Site Number 392004 | Suita-Shi | Japan |
| FG002 | Alirocumab 75 mg Q2W | Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| FG003 | Alirocumab 150 mg Q2W | Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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Randomized population.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo (for alirocumab) Q2W for 12-weeks in combination with atorvastatin stable dose. |
| BG001 | Alirocumab 50 mg Q2W | Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| BG002 | Alirocumab 75 mg Q2W | Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| BG003 | Alirocumab 150 mg Q2W | Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| BG004 | 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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| Low-Density Lipoprotein Cholesterol (LDL-C) in mmol/L | Mean | Standard Deviation | mmol/L |
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| LDL-C in mg/dL | Mean | Standard Deviation | mg/dL |
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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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Calculated LDL-C at Week 12 - On-Treatment Analysis | Calculated LDL-C values were obtained using the Friedewald formula. Baseline adjusted least squares (LS) means and standard errors were estimated using an analysis of covariance (ANCOVA) model including available post-baseline data on treatment from first investigational product (IP) injection up to 21 days after last IP injection (on-treatment analysis). Missing Week 12 data were imputed by last observation carried forward [LOCF] method. | Modified Intent-To-Treat (mITT) population included all randomized participants with one baseline and at least one post-baseline calculated LDL-C value on-treatment. | Posted | Least Squares Mean | Standard Error | percent change | Baseline to Week 12 (LOCF) |
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| Secondary | Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 12 - On-Treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | mITT population. | Posted | Least Squares Mean | Standard Error | mmol/L | Baseline to Week 12 (LOCF) |
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| Secondary | Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 12 - On-Treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | mITT population. | Posted | Least Squares Mean | Standard Error | mg/dL | Baseline to Week 12 (LOCF) |
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| Secondary | Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 12 - On-Treatment Analysis | mITT population. | Posted | Number | percentage of participants | Week 12 (LOCF) |
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| Secondary | Percent Change From Baseline in Total Cholesterol, High-Density Lipoprotein Cholesterol (HDL-C), Non-HDL-C, and Apolipoprotein B (Apo-B) at Week 12 - On-Treatment Analysis | Adjusted LS means and standard errors were estimated using the same ANCOVA model as for primary endpoint. | Participants of the mITT population with one baseline and at least one post baseline on-treatment value of lipid parameters analyzed. | Posted | Least Squares Mean | Standard Error | percent change | Baseline to Week 12 (LOCF) |
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| Secondary | Percent Change From Baseline in Fasting Triglycerides and Lipoprotein (a) at Week 12 - On-Treatment Analysis | Since the assumptions of normal distribution and equality of variances were not verified for the lipid parameters, percent changes were expressed as median (inter-quartile range). | Participants of the mITT population with one baseline and at least one post baseline on-treatment value of Fasting Triglycerides and Lipoprotein (a) analyzed. | Posted | Median | Inter-Quartile Range | percent change | Baseline to Week 12 (LOCF) |
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| Secondary | Absolute Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) Ratio at Week 12 - On-Treatment Analysis | Adjusted LS mean and standard errors were estimated using the same ANCOVA as for primary endpoint. | Participants of the mITT population with one baseline and at least one post baseline on-treatment value of ApoB/ApoA-1 ratio analyzed. | Posted | Least Squares Mean | Standard Error | ratio | From Baseline to Week 12 (LOCF) |
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All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 20) regardless of seriousness or relationship to investigational medicinal product (IMP).
Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during the 'treatment emergent period' (the time from the first dose to the last dose of IMP + 70 days). Safety population: participants who received at least one dose or partial dose of IMP.
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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 Q2W for 12 weeks in combination with atorvastatin stable dose. | 1 | 25 | 5 | 25 | ||
| EG001 | Alirocumab 50 mg Q2W | Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. | 0 | 25 | 11 | 25 | ||
| EG002 | Alirocumab 75 mg Q2W | Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose. | 0 | 25 | 8 | 25 | ||
| EG003 | Alirocumab 150 mg Q2W | Alirocumab 150 mg Q2W for 12-weeks in combination with atorvastatin stable dose. | 1 | 25 | 9 | 25 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 16.1 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 16.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 16.1 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
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If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Transparency Team | Sanofi | Contact --US@sanofi.com |
| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C571059 | alirocumab |
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
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| Male |
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| ANCOVA | <0.0001 | Threshold for significance ≤0.05 | 2-Sided | No | Superiority or Other |
| ANCOVA | <0.0001 | Threshold for significance ≤0.05 | 2-Sided | No | Superiority or Other |
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