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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)

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01507831
First received: January 6, 2012
Last updated: November 18, 2015
Last verified: November 2015
Results First Received: November 18, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Hypercholesterolemia
Interventions: Drug: Placebo (for alirocumab)
Drug: Alirocumab
Drug: Lipid-Modifying Therapy (LMT)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 320 centers in 27 countries. Overall, 5144 participants were screened between January 2012 and March 2013, 2801 of whom were screen failures. Screen failures were mainly due to exclusion criteria met. In addition 2 participants received study drug but did not undergo randomization. They were excluded from analysis.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified as per diagnosis of heterozygous familial hypercholesterolemia (heFH), prior history of myocardial infarction (MI) or ischemic stroke, intensity of statin treatment and geographic region. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo:alirocumab).

Reporting Groups
  Description
Placebo Q2W Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable lipid modifying therapy (LMT) for 78 weeks.
Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.

Participant Flow:   Overall Study
    Placebo Q2W     Alirocumab 150 mg Q2W  
STARTED     788 [1]   1553 [1]
Treated     788     1550  
COMPLETED     595     1113  
NOT COMPLETED     193     440  
Randomized but not treated                 0                 3  
Adverse Event                 48                 113  
Death                 6                 2  
Poor compliance to protocol                 38                 60  
Physician Decision                 0                 4  
Participant moved                 5                 19  
Consent withdrawn by participant                 34                 72  
Related to study drug administration                 5                 14  
Last visit outside protocol visit window                 51                 143  
Selection criteria finally not met                 0                 1  
Site closure                 0                 3  
Potential lost to follow-up                 3                 0  
Unspecified                 3                 6  
[1] Randomized



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo Q2W Placebo (for alirocumab) SC injection Q2W added to stable LMT for 78 weeks.
Alirocumab 150 mg Q2W Alirocumab 150 mg SC injection Q2W added to stable LMT for 78 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo Q2W     Alirocumab 150 mg Q2W     Total  
Number of Participants  
[units: participants]
  788     1553     2341  
Age  
[units: years]
Mean (Standard Deviation)
  60.6  (10.4)     60.4  (10.4)     60.5  (10.4)  
Gender  
[units: participants]
     
Female     314     570     884  
Male     474     983     1457  
Calculated LDL-C in mg/dL [1]
[units: mg/dL]
Mean (Standard Deviation)
  121.9  (41.4)     122.7  (42.6)     122.4  (42.2)  
Calculated LDL-C in mmol/L  
[units: mmol/L]
Mean (Standard Deviation)
  3.157  (1.073)     3.178  (1.102)     3.171  (1.092)  
[1] Calculated LDL-C in mg/dL from Friedewald formula (LDL-C = Total cholesterol - High-density lipoprotein cholesterol - [Triglyceride/5]).



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Who Experienced Adverse Events (AEs)   [ Time Frame: Up to 10 weeks after last study drug administration (maximum of 86 weeks) ]

2.  Secondary:   Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis   [ Time Frame: From Baseline to Week 52 ]

3.  Secondary:   Percent Change From Baseline in Calculated LDL-C at Week 24 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

4.  Secondary:   Percent Change From Baseline in Calculated LDL-C at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

5.  Secondary:   Percent Change From Baseline in Calculated LDL-C at Week 12 - On-treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

6.  Secondary:   Percent Change From Baseline in Measured LDL-C at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

7.  Secondary:   Percent Change From Baseline in Apolipoprotein (Apo) B at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

8.  Secondary:   Percent Change From Baseline in Apo B at Week 24 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

9.  Secondary:   Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

10.  Secondary:   Percent Change From Baseline in Non-HDL-C at Week 24 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

11.  Secondary:   Percent Change From Baseline in Total Cholesterol (Total-C) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

12.  Secondary:   Percent Change From Baseline in Apo B at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

13.  Secondary:   Percent Change From Baseline in Non-HDL-C at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

14.  Secondary:   Percent Change From Baseline in Total-C at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

15.  Secondary:   Percentage of Very High Cardiovascular (CV) Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis   [ Time Frame: Up to Week 52 ]

16.  Secondary:   Percentage of Very High CV Risk Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) or High CV Risk Participants Reaching Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - On-Treatment Analysis   [ Time Frame: Up to Week 52 ]

17.  Secondary:   Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - ITT Analysis   [ Time Frame: Up to Week 52 ]

18.  Secondary:   Percentage of Participants Reaching Calculated LDL-C <70 mg/dL (1.81 mmol/L) at Week 24 - On-Treatment Analysis   [ Time Frame: Up to Week 52 ]

19.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

20.  Secondary:   Percent Change From Baseline in HDL-C at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

21.  Secondary:   Percent Change From Baseline in Fasting Triglycerides at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

22.  Secondary:   Percent Change From Baseline in Apo A1 at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

23.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

24.  Secondary:   Percent Change From Baseline in HDL-C at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

25.  Secondary:   Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

26.  Secondary:   Percent Change From Baseline in Apo A1 at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

27.  Other Pre-specified:   Percent Change From Baseline in Calculated LDL-C at Week 52 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

28.  Other Pre-specified:   Percent Change From Baseline in Calculated LDL-C at Week 52 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 52 ]

29.  Other Pre-specified:   Percent Change From Baseline in Calculated LDL-C at Week 78 - ITT Analysis   [ Time Frame: From Baseline to Week 78 ]

30.  Other Pre-specified:   Percent Change From Baseline in Calculated LDL-C at Week 78 - On-Treatment Analysis   [ Time Frame: From Baseline to Week 78 ]

31.  Other Pre-specified:   Percentage of Participants Who Experienced Cardiovascular (CV) Events   [ Time Frame: Up to 10 weeks after last study drug administration (maximum of 86 weeks) ]

32.  Post-Hoc:   Percentage of Participants Who Experienced Major Adverse CV Events   [ Time Frame: Up to 10 weeks after last study drug administration (maximum of 86 weeks) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Manual reclassification was done by the Sponsor for the "other reasons" of non-completion of study as specified in the electronic case report (eCRF) form.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact-US@sanofi.com


Publications of Results:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01507831     History of Changes
Other Study ID Numbers: LTS11717
2011-002806-59 ( EudraCT Number )
U1111-1121-3928 ( Other Identifier: UTN )
Study First Received: January 6, 2012
Results First Received: November 18, 2015
Last Updated: November 18, 2015
Health Authority: United States: Food and Drug Administration