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Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)

This study has been completed.
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01730040
First received: November 9, 2012
Last updated: July 29, 2015
Last verified: July 2015
Results First Received: July 29, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Hypercholesterolemia
Interventions: Drug: Alirocumab
Drug: Atorvastatin
Drug: Ezetimibe
Drug: Rosuvastatin
Drug: Placebo

  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 85 sites in 9 countries. Overall, 859 subjects were screened between 24 October 2012 and 26 September 2013, 504 of whom were screen failures. Screen failures ware 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 or ischemic stroke, and intensity of statin treatment (atorvastatin 20 or 40 mg). Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1:1:1:1:1:1 ratio after confirmation of selection criteria.

Reporting Groups
  Description
Atorvastatin 40 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.
Ezetimibe 10 mg + Atorvastatin 20 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Atorvastatin 80 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.
Rosuvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received rosuvastatin 40 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.
Ezetimibe 10 mg + Atorvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.

Participant Flow:   Overall Study
    Atorvastatin 40 mg     Ezetimibe 10 mg + Atorvastatin 20 mg     Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg     Atorvastatin 80 mg     Rosuvastatin 40 mg     Ezetimibe 10 mg + Atorvastatin 40 mg     Alirocumab 75 mg/up to 150 mg + Atorvastatin 40 mg  
STARTED     57     55     57     47     45     47     47  
Treated     57     55     57     47     45     46     47  
COMPLETED     44     40     46     39     39     40     38  
NOT COMPLETED     13     15     11     8     6     7     9  
Randomized but not treated                 0                 0                 0                 0                 0                 1                 0  
Subject moved                 0                 0                 1                 0                 0                 0                 1  
Physician Decision                 0                 0                 0                 0                 0                 1                 1  
Other than specified                 7                 8                 5                 5                 5                 4                 4  
Adverse Event                 4                 3                 5                 3                 1                 1                 2  
Poor compliance to protocol                 2                 4                 0                 0                 0                 0                 1  



  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
Atorvastatin 40 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received atorvastatin 40 mg over-encapsulated tablets orally once daily (QD), placebo for alirocumab SC injection every two weeks (Q2W), and placebo for ezetimibe over-encapsulated tablets orally QD added to stable Lipid-Modifying Therapy (LMT) for 24 weeks.
Ezetimibe 10 mg + Atorvastatin 20 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg Participants, who were receiving atorvastatin 20 mg over-encapsulated tablets orally at baseline, received Alirocumab 75 mg SC injection Q2W, atorvastatin 20 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Atorvastatin 80 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received Atorvastatin 80 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.
Rosuvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received rosuvastatin 40 mg over-encapsulated tablets orally QD, placebo for alirocumab SC injection Q2W, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks.
Ezetimibe 10 mg + Atorvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received ezetimibe 10 mg over-encapsulated tablets orally QD, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for alirocumab SC injection Q2W added to stable LMT for 24 weeks.
Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg Participants, who were receiving atorvastatin 40 mg over-encapsulated tablets orally at baseline, received alirocumab 75 mg SC injection Q2W, atorvastatin 40 mg over-encapsulated tablets orally QD, and placebo for ezetimibe over-encapsulated tablets orally QD added to stable LMT for 24 weeks. Alirocumab dose up-titrated to 150 mg Q2W from Week 12 when LDL-C levels ≥70 mg/dL (1.81 mmol/L) or ≥100 mg/dL (2.59 mmol/L) at Week 8, based on baseline disease characteristic and medical history.
Total Total of all reporting groups

Baseline Measures
    Atorvastatin 40 mg     Ezetimibe 10 mg + Atorvastatin 20 mg     Alirocumab 75 mg/up to 150 mg + Atorvastatin 20 mg     Atorvastatin 80 mg     Rosuvastatin 40 mg     Ezetimibe 10 mg + Atorvastatin 40 mg     Alirocumab 75 mg/ up to 150 mg + Atorvastatin 40 mg     Total  
Number of Participants  
[units: participants]
  57     55     57     47     45     47     47     355  
Age  
[units: years]
Mean (Standard Deviation)
  63  (9.91)     65.7  (8.96)     62.2  (10.03)     63.2  (10.89)     57.5  (9.96)     63.9  (10.33)     64.2  (10.36)     62.9  (10.2)  
Gender  
[units: participants]
               
Female     22     24     24     14     13     11     16     124  
Male     35     31     33     33     32     36     31     231  
Low density lipoprotein cholesterol (LDL-C) in mg/dL [1]
[units: mg/dL]
Mean (Standard Deviation)
  100.3  (29.8)     100.4  (29.5)     103.9  (34.9)     108.6  (37.5)     109.8  (39.0)     98.9  (29.2)     116.4  (37.4)     105.1  (34.1)  
LDL-C in mmol/L [1]
[units: mmol/L]
Mean (Standard Deviation)
  2.957  (0.773)     2.599  (0.765)     2.692  (0.905)     2.813  (0.97)     2.844  (1.011)     2.562  (0.756)     3.016  (0.968)     2.723  (0.884)  
[1] Calculated LDL-C from Friedewald formula.



  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 24 ]

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

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

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

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

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

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 24 ]

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

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

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

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

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

13.  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 - ITT Analysis   [ Time Frame: Up to Week 24 ]

14.  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 24 ]

15.  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 24 ]

16.  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 24 ]

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

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

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

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

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

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

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

24.  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
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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: Clinical Trial Management
Organization: Regeneron Pharmaceuticals, Inc
e-mail: clinicaltrials@regeneron.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01730040     History of Changes
Other Study ID Numbers: R727-CL-1110
Study First Received: November 9, 2012
Results First Received: July 29, 2015
Last Updated: July 29, 2015
Health Authority: United States: Food and Drug Administration