Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02715726 | Evaluation of Alirocumab Versus Ezetimibe on Top of Statin in Asia in High Cardiovascular Risk Patients With Hypercholesterolemia | PHASE3 | COMPLETED | 615 | — | — | Jul 27, 2016 | Aug 6, 2018 | Sep 30, 2019 | 62 | China, India +1 |
| NCT02584504 | Efficacy and Safety of Alirocumab in Patients With Hypercholesterolemia Not Adequately Controlled With Non-statin Lipid Modifying Therapy or the Lowest Strength of Statin | PHASE3 | COMPLETED | 163 | — | — | Nov 30, 2015 | Jan 9, 2018 | Jan 23, 2019 | 30 | Japan |
| NCT02289963 | Evaluation of Alirocumab in Addition to Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia in South Korea and Taiwan | PHASE3 | COMPLETED | 199 | — | — | Jan 1, 2015 | Apr 1, 2016 | Jun 26, 2017 | 27 | South Korea, Taiwan |
| NCT02107898 | Efficacy and Safety Evaluation of Alirocumab in Patients With Heterozygous Familial Hypercholesterolemia or High Cardiovascular Risk Patients With Hypercholesterolemia on Lipid Modifying Therapy (ODYSSEY JAPAN) | PHASE3 | COMPLETED | 216 | — | — | Mar 1, 2014 | Sep 1, 2015 | Oct 4, 2016 | 32 | Japan |
| NCT01954394 | Open Label Study of Long Term Safety Evaluation of Alirocumab | PHASE3 | COMPLETED | 986 | — | — | Dec 17, 2013 | Jun 30, 2017 | Jul 24, 2018 | 177 | United States, Argentina +22 |
| NCT02023879 | Phase III Study To Evaluate Alirocumab in Patients With Hypercholesterolemia Not Treated With a Statin (ODYSSEY CHOICE II) | PHASE3 | COMPLETED | 233 | — | — | Dec 16, 2013 | Jun 30, 2017 | Jul 27, 2018 | 43 | United States, Australia +6 |
| NCT01644188 | Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY COMBO II) | PHASE3 | COMPLETED | 720 | — | — | Aug 1, 2012 | Jul 1, 2015 | Aug 4, 2016 | 126 | United States, Canada +8 |
| NCT01623115 | Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy | PHASE3 | COMPLETED | 486 | — | — | Jul 1, 2012 | Dec 1, 2014 | Feb 8, 2016 | 91 | United States, Austria +12 |
| NCT01644175 | Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With High Cardiovascular Risk and Hypercholesterolemia (ODYSSEY COMBO I) | PHASE3 | COMPLETED | 316 | — | — | Jul 1, 2012 | Apr 1, 2014 | Nov 6, 2015 | 76 | United States |
| NCT01644474 | Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia | PHASE3 | COMPLETED | 103 | — | — | Jul 1, 2012 | Jul 1, 2013 | Nov 6, 2015 | 8 | United States, Belgium +2 |
| NCT01507831 | Long-term Safety and Tolerability of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY Long Term) | PHASE3 | COMPLETED | 2,341 | — | — | Jan 1, 2012 | Nov 1, 2014 | Dec 22, 2015 | 320 | United States, Argentina +25 |
| NCT01812707 | Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy in Japan | PHASE2 | COMPLETED | 100 | — | — | Mar 1, 2013 | Jan 1, 2014 | Oct 4, 2016 | 4 | Japan |
| NCT01288469 | Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) When Co-administered With High Dose of Atorvastatin in Patients With Primary Hypercholesterolemia | PHASE2 | COMPLETED | 92 | — | — | Jan 1, 2011 | Sep 1, 2011 | Sep 24, 2015 | 20 | United States |
| NCT01288443 | Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy | PHASE2 | COMPLETED | 183 | — | — | Jan 1, 2011 | Dec 1, 2011 | Sep 24, 2015 | 38 | United States |
| NCT01959971 | Effect of Alirocumab on Lipid Metabolism in Adults With Elevated LDL-Cholesterol | PHASE1 | COMPLETED | 20 | — | — | Dec 1, 2013 | May 1, 2015 | May 2, 2017 | 1 | United States |
| NCT01723735 | Effect of Alirocumab (SAR236553/REGN727) Administered on Top of Ezetimibe or Fenofibrate on Lipid Profiles in Healthy Subjects | PHASE1 | COMPLETED | 79 | — | — | Nov 1, 2012 | Jul 1, 2013 | Sep 28, 2016 | 2 | France |
| NCT01448317 | Ascending Dose Study of the Safety and Tolerability of Alirocumab (SAR236553/REGN727) in Japanese Healthy Volunteers | PHASE1 | COMPLETED | 32 | — | — | May 1, 2011 | Jan 1, 2012 | Sep 28, 2016 | 1 | Japan |
Adjusted least square (LS) means and standard errors at Week 24 were obtained from mixed models analysis with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Adjusted Least-squares (LS) means and standard errors at Week 12 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 12 regardless of status on- or off-treatment were used in the model (ITT analysis).
Adjusted Least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data up to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Adjusted least-squares (LS) means and standard errors at Week 24 were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data. All available post-baseline data from Week 4 to Week 24 regardless of status on- or off-treatment were used in the model (ITT analysis).
Reported AEs are treatment-emergent AEs that is AEs that developed/worsened during the 'treatment-emergent period' (the time from the first dose of alirocumab in this study up to the last dose of alirocumab received in this study +70 days). Clinically significant lab and vital sign abnormalities were to be reported as AEs.
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.
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 8 data were imputed by last observation carried forward \[LOCF\] method.
| Arm | Type | Description |
|---|---|---|
| Ezetimibe 10 mg | ACTIVE_COMPARATOR | Oral ezetimibe 10 mg capsule once daily with or without food for 24 weeks and subcutaneous placebo injection for alirocumab every 2 weeks (Q2W) for 22 weeks added to lipid modifying therapy (LMT). |
| Alirocumab 75 mg Q2W/up to 150 mg Q2W | EXPERIMENTAL | Subcutaneous injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe once daily with or without food added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C level was \>=70 milligrams per deciliter (mg/dL) (1.81 millimoles per liter \[mmol/L\]) at Week 8. |
| Alirocumab 150 mg Q4W | EXPERIMENTAL | Double-blind treatment period(DBTP):participants received Alirocumab 150 mg subcutaneous injection every 4 week(Q4W) alternating with placebo(for alirocumab)Q4W added to lowest-strength statin therapy(atorvastatin 5 mg daily),stable non-statin LMT/diet therapy alone for 12weeks. Participants completed DBTP,entered open-label treatment period(OLTP),received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg every 2 weeks(Q2W) at Week 24(OLTP:Week 12),when targeted LDL-C level at Week 20 not achieved as Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012:1) ≥100 mg/dL(2.59 mmol/L) in heterozygous familial hypercholesterolemia (heFH) participants/non-familial hypercholesterolemia (non-FH)participants with history of documented coronary heart disease;2) ≥120 mg/dL(3.10 mmol/L)in non-FH participants with history of documented diseases/other risk factors as categorized in primary prevention category III) |
| Alirocumab 150 mg Q2W | EXPERIMENTAL | In DBTP, participants received Alirocumab 150 mg subcutaneous (SC) injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg daily), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when targeted LDL-C levels at Week 20 were not achieved i.e. LDL-C ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) according to Japan Atherosclerosis Society(JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. |
| Placebo Q2W | PLACEBO_COMPARATOR | In DBTP, participants received Placebo (for alirocumab) SC injection Q2W added to lowest-strength statin therapy (atorvastatin 5 mg), stable non-statin LMT or diet therapy alone for 12 weeks. Participants who completed DBTP were entered in OLTP and received alirocumab 150 mg Q4W up to additional 52 weeks. Alirocumab dose up-titrated to 150 mg Q2W at Week 24 (Week 12 of OLTP), when targeted LDL-C levels at Week 20 were not achieved i.e. LDL-C ≥100 mg/dL (2.59 mmol/L) or ≥120 mg/dL (3.10 mmol/L) according to JAS Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012. |
| Alirocumab 75 mg/Up to 150 mg Q2W | EXPERIMENTAL | Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels above pre-specified threshold at Week 8 as defined in Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012 i.e. * ≥100 mg/dL (2.59 mmol/L) in heFH participants or in non-familial hypercholesterolemia (non-FH) participants who had a history of documented coronary heart disease (CHD) * ≥120 mg/dL (3.10 mmol/L) in non-FH participants who had a history of documented diseases or other risk factors as categorized in primary prevention category III |
| Alirocumab 75 or 150 mg Q2W | EXPERIMENTAL | Alirocumab 75 mg or 150 mg every 2 weeks (Q2W) added to stable lipid-modifying therapy (LMT) for up to 168 additional weeks (or until the product was commercially available) in participants who completed the parent studies EFC12492, R727-CL-1112, EFC12732 and LTS11717. |
| Alirocumab 75 mg Q2W/Up to 150 mg Q2W (Calibrator) | OTHER | Period 1: Alirocumab 75 mg SC injection Q2W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. |
| Alirocumab 150 mg Q4W/Up to 150 mg Q2W | EXPERIMENTAL | Period 1: Alirocumab 150 mg SC injection Q4W alternating with placebo (for alirocumab) Q4W added to stable non-statin LMT or diet alone for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when targeted LDL-C levels at Week 8 were not achieved i.e. LDL-C ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) depending on cardiovascular risk or \<30% LDL-C reduction from baseline. Period 2: Alirocumab 150 mg SC injection Q4W from Week 24 until second quarter 2017 or until the drug is commercially available in the country, whatever occurred first. Alirocumab dose could be either up-titrated to 150 mg Q2W from Week 36 or maintained according to the investigator judgement and LDL-C values. Subsequent down titration to 150 mg Q4W was allowed. |
| Alirocumab 75 /up to 150 mg Q2W | EXPERIMENTAL | Alirocumab 75 mg every 2 weeks (Q2W) and oral placebo capsule for ezetimibe daily added to stable Lipid Modifying Therapy (LMT) for 104 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C level ≥70 mg/dL (1.81 mmol/L) at Week 8. |
| Placebo | PLACEBO_COMPARATOR | Placebo for alirocumab every 2 weeks (Q2W) on top of stable lipid-modifying therapy (LMT) for 78 weeks. |
| Alirocumab | EXPERIMENTAL | Alirocumab 75 mg Q2W added to stable LMT for 52 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. |
| Alirocumab 75/Up to 150 mg Q2W | EXPERIMENTAL | SC injection of alirocumab 75 mg Q2W and oral placebo capsule for ezetimibe daily for 24 weeks. Alirocumab dose up-titrated to 150 mg from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) at Week 8. |
| Alirocumab 50 mg Q2W | EXPERIMENTAL | Alirocumab 50 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Alirocumab 75 mg Q2W | EXPERIMENTAL | Alirocumab 75 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Placebo + Atorvastatin 80 mg | PLACEBO_COMPARATOR | Placebo (for alirocumab) subcutaneous (SC) administration every 2 weeks (Q2W) in combination with atorvastatin 80 mg orally once daily for 8 weeks. |
| Alirocumab + Atorvastatin 10 mg | EXPERIMENTAL | Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks. |
| Alirocumab + Atorvastatin 80 mg | EXPERIMENTAL | Alirocumab 150 mg SC administration Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks. |
| Alirocumab 100 mg Q2W | EXPERIMENTAL | Alirocumab 100 mg Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Alirocumab 200 mg Q4W | EXPERIMENTAL | Alirocumab 200 mg every 4 weeks (Q4W) and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Alirocumab 300 mg Q4W | EXPERIMENTAL | Alirocumab 300 mg Q4W and alternating placebo Q2W for 12-weeks in combination with atorvastatin stable dose. |
| Placebo - Alirocumab | EXPERIMENTAL | Injection through subcutaneous (SC) administration, placebo for 4 weeks then, alirocumab for 10 weeks |
| Alirocumab + Ezetimibe Placebo | EXPERIMENTAL | Subcutaneous (SC) injections of alirocumab added to oral administration of ezetimibe placebo |
| Alirocumab + Ezetimibe | EXPERIMENTAL | Subcutaneous (SC) injections of alirocumab added to oral administration of ezetimibe |
| Alirocumab + Fenofibrate | EXPERIMENTAL | Subcutaneous (SC) injections of alirocumab added to oral administration of fenofibrate |
| Cohort 1 | EXPERIMENTAL | Alirocumab dose 1 versus placebo |
| Cohort 2 | EXPERIMENTAL | Alirocumab dose 2 versus placebo |
| Cohort 3 | EXPERIMENTAL | Alirocumab dose 3 versus placebo |
| Cohort 4 | EXPERIMENTAL | Alirocumab dose 4 versus placebo |
| Name | Type | Description |
|---|---|---|
| Alirocumab | DRUG | Pharmaceutical form:solution Route of administration: subcutaneous |
| Placebo for alirocumab | DRUG | Pharmaceutical form:solution Route of administration: subcutaneous |
| ezetimibe | DRUG | Pharmaceutical form:capsule Route of administration: oral |
| placebo for ezetimibe | DRUG | Pharmaceutical form:capsule Route of administration: oral |
| atorvastatin | DRUG | Pharmaceutical form:tablet Route of administration: oral |
| rosuvastatin | DRUG | Pharmaceutical form:tablet Route of administration: oral |
| simvastatin | DRUG | Pharmaceutical form:tablet Route of administration: oral |
| Placebo | DRUG | Solution for injection, one subcutaneous injection in the abdomen, thigh, or outer area of upper arm with a disposable auto-injector. |
| Non-statin Lipid-Modifying Therapy | DRUG | Ezetimibe, Bezafibrate or Fenofibrate at stable dose as background therapy. |
| Diet Alone | OTHER | Stable cholesterol-lowering diet as background therapy. |
| Placebo (for Alirocumab) | DRUG | Solution for injection, one subcutaneous injection in the abdomen with a disposable auto-injector. |
| Lipid-Modifying Therapy (LMT) | DRUG | Statins (Rosuvastatin, Simvastatin or Atorvastatin) at stable dose with or without other LMT as clinically indicated. |
| Non-statin LMT | DRUG | Ezetimibe or Fenofibrate at stable dose as background therapy. |
| Placebo (for ezetimibe) | DRUG | One capsule once daily orally at approximately the same time of the day with or without food. |
| Lipid Modifying Therapy (LMT) | DRUG | Statin (rosuvastatin, simvastatin or atorvastatin) at stable dose. |
| Placebo (for atorvastatin) | DRUG | One over-encapsulated tablet of placebo for atorvastatin orally once daily in the evening with dinner. |
| Ezetimibe Placebo | DRUG | Pharmaceutical form: capsule Route of administration: oral |
| Fenofibrate | DRUG | Pharmaceutical form: tablet Route of administration: oral |
| Alirocumab (Solution) | DRUG | Pharmaceutical form: solution Route of administration: subcutaneous |
| Alirocumab (Lyophilized formulation) | DRUG | Pharmaceutical form: lyophilized formulation Route of administration: subcutaneous |
| Placebo (Solution) | DRUG | Pharmaceutical form: solution Route of administration: subcutaneous |
| Placebo (Lyophilized formulation) | DRUG | Pharmaceutical form: lyophilized formulation Route of administration: Subcutaneous |
Inclusion criteria: Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who are not adequately controlled with a maximally tolerated daily dose of statin at a stable dose for at least 4 weeks prior to the screening visit (Week -3). Exclusion ...