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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)

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01644175
First received: July 16, 2012
Last updated: October 7, 2015
Last verified: October 2015
Results First Received: August 20, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy 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 76 centers in the United States of America. Overall, 640 participants were screened between July 2012 and February 2013, 324 of whom were screen failures. Screen failures were mainly due to exclusion criteria met.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified according to prior history of myocardial infarction (MI) or ischemic stroke, and intensity of statin treatment. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:2 ratio (placebo: alirocumab) after confirmation of selection criteria. 316 participants were randomized.

Reporting Groups
  Description
Placebo Q2W Placebo (for alirocumab) subcutaneous (SC) injection every 2 weeks (Q2W) added to stable Lipid-Modifying Therapy (LMT) for 52 weeks.
Alirocumab 75/150 mg Q2W Alirocumab 75 mg SC injection 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.

Participant Flow:   Overall Study
    Placebo Q2W     Alirocumab 75/150 mg Q2W  
STARTED     107 [1]   209 [1]
Treated     107     207  
COMPLETED     75     156  
NOT COMPLETED     32     53  
Randomized But Not Treated                 0                 2  
Adverse Event                 8                 13  
Death                 1                 2  
Poor compliance to protocol                 9                 10  
Physician Decision                 1                 2  
Participant Moved                 1                 2  
Consent withdrawn by participant                 3                 4  
Related to Autoinjector Administration                 2                 1  
Last visit outside protocol visit window                 4                 11  
Selection criteria finally not met                 0                 1  
Site closure                 2                 2  
Lost to Follow-up                 1                 0  
Other than specified above                 0                 3  
[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 52 weeks.
Alirocumab 75/150 mg Q2W Alirocumab 75 mg SC injection 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.
Total Total of all reporting groups

Baseline Measures
    Placebo Q2W     Alirocumab 75/150 mg Q2W     Total  
Number of Participants  
[units: participants]
  107     209     316  
Age  
[units: years]
Mean (Standard Deviation)
  63.0  (8.8)     63.0  (9.5)     63.0  (9.3)  
Gender  
[units: participants]
     
Female     30     78     108  
Male     77     131     208  
Calculated LDL-C in mmol/L [1]
[units: mmol/L]
Mean (Standard Deviation)
  2.746  (0.915)     2.595  (0.764)     2.646  (0.820)  
Calculated LDL-C in mg/dL [2]
[units: mg/dL]
Mean (Standard Deviation)
  106.0  (35.3)     100.2  (29.5)     102.2  (31.6)  
[1] Calculated LDL-C in mmol/L from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/2.2]).
[2] Calculated LDL-C in mg/dL from Friedewald formula (LDL cholesterol = Total cholesterol - HDL cholesterol - [Triglyceride/5]).



  Outcome Measures
  Show All Outcome Measures

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

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

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

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

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

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

7.  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 ]

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

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

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

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

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

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

14.  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 ]

15.  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 ]

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

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

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

19.  Secondary:   Percent Change From Baseline in Apolipoprotein A-1 at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]

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

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

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

23.  Secondary:   Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 52 ]


  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
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  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:
Other Publications:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01644175     History of Changes
Other Study ID Numbers: EFC11568
U1111-1121-4356 ( Other Identifier: UTN )
Study First Received: July 16, 2012
Results First Received: August 20, 2015
Last Updated: October 7, 2015
Health Authority: United States: Food and Drug Administration