Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia (ODYSSEY MONO)

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01644474
First received: July 17, 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: Alirocumab
Drug: Ezetimibe
Drug: Placebo (for Alirocumab)
Drug: Placebo (for Ezetimibe)

  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 8 centers in 4 countries. A total of 204 participants were screened between July 2012 and November 2012, 101 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 the diabetes mellitus status. Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1 ratio ( alirocumab:ezetimibe) after confirmation of selection criteria. 103 participants were randomized.

Reporting Groups
  Description
Ezetimibe 10 mg Oral ezetimibe 10 mg capsule daily and subcutaneous (SC) placebo injection for alirocumab every 2 weeks (Q2W) for 24 weeks.
Alirocumab 75/Up to 150 mg Q2W 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 low density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL (1.81 mmol/L) at Week 8.

Participant Flow:   Overall Study
    Ezetimibe 10 mg     Alirocumab 75/Up to 150 mg Q2W  
STARTED     51 [1]   52 [1]
Treated     51     52  
COMPLETED     44     44  
NOT COMPLETED     7     8  
Poor compliance to protocol                 1                 0  
Consent withdrawn by participant                 0                 1  
Participant moved                 0                 1  
Adverse Event                 4                 5  
Site scheduling error                 1                 1  
Protocol Violation                 1                 0  
[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
Ezetimibe 10 mg Oral ezetimibe 10 mg capsule daily and SC placebo injection for alirocumab Q2W for 24 weeks.
Alirocumab 75/Up to 150 mg Q2W 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.
Total Total of all reporting groups

Baseline Measures
    Ezetimibe 10 mg     Alirocumab 75/Up to 150 mg Q2W     Total  
Number of Participants  
[units: participants]
  51     52     103  
Age  
[units: years]
Mean (Standard Deviation)
  59.6  (5.3)     60.8  (4.6)     60.2  (5.0)  
Gender  
[units: participants]
     
Female     24     24     48  
Male     27     28     55  
Calculated LDL-C in mmol/L [1]
[units: mmol/L]
Mean (Standard Deviation)
  3.58  (0.6)     3.65  (0.7)     3.62  (0.7)  
Calculated LDL-C in mg/dL [2]
[units: mg/dL]
Mean (Standard Deviation)
  138.3  (24.5)     141.1  (27.1)     139.7  (25.8)  
[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
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1.  Primary:   Percent Change From Baseline in Calculated LDL-C at Week 24 - Intent-to-Treat (ITT) Analysis   [ Time Frame: From Baseline to Week 24 ]

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

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

4.  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 24 ]

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

6.  Secondary:   Percent Change From Baseline in Apo B at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 24 ]

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

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

9.  Secondary:   Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) at Week 24 - ITT Analysis   [ Time Frame: Up to Week 24 ]

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

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

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

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

14.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 24 ]

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

16.  Secondary:   Percent Change From Baseline in Fasting Triglycerides at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 24 ]

17.  Secondary:   Percent Change From Baseline in Apolipoprotein A-1 (Apo A-1) at Week 24 - ITT Analysis   [ Time Frame: From Baseline to Week 24 ]

18.  Secondary:   Percent Change From Baseline in Apo A-1 at Week 12 - ITT Analysis   [ Time Frame: From Baseline to Week 24 ]


  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
Due to administrative error in the automated process (which was detected after database lock), planned dose up­titration criteria for LDL­C levels was changed from ≥100 mg/dL to ≥70 mg/dL.


  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: NCT01644474     History of Changes
Other Study ID Numbers: EFC11716
U1111-1124-1167 ( Other Identifier: UTN )
2011-001424-38 ( EudraCT Number )
Study First Received: July 17, 2012
Results First Received: August 20, 2015
Last Updated: October 7, 2015
Health Authority: United States: Food and Drug Administration