Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) When Co-administered With High Dose of Atorvastatin in Patients With Primary Hypercholesterolemia

This study has been completed.
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01288469
First received: February 1, 2011
Last updated: August 21, 2015
Last verified: January 2015
Results First Received: August 21, 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: Placebo (for alirocumab)
Drug: Atorvastatin
Drug: Placebo (for atorvastatin)

  Participant Flow
  Hide Participant Flow

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 20 centers in the United States of America. Overall, 214 participants were screened between January 2011 and April 2011. 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
Assignment to treatment arms was done centrally using an Interactive Voice/Web Response System in a 1:1:1 ratio after confirmation of selection criteria. 92 participants were randomized.

Reporting Groups
  Description
Placebo + Atorvastatin 80 mg Placebo (for alirocumab) subcutaneous (SC) injection every two weeks (Q2W) in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Alirocumab + Atorvastatin 10 mg Alirocumab 150 mg SC injection Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.
Alirocumab + Atorvastatin 80 mg Alirocumab 150 mg SC injection Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.

Participant Flow:   Overall Study
    Placebo + Atorvastatin 80 mg     Alirocumab + Atorvastatin 10 mg     Alirocumab + Atorvastatin 80 mg  
STARTED     31 [1]   31 [1]   30 [1]
Treated     31     31     30  
COMPLETED     24     28     28  
NOT COMPLETED     7     3     2  
Adverse Event                 4                 1                 1  
Poor compliance to protocol                 0                 1                 0  
Participant Moved                 1                 0                 0  
Consent withdrawn by subject                 1                 1                 1  
Exclusion criteria finally met                 1                 0                 0  
[1] Randomized



  Baseline Characteristics
  Hide Baseline Characteristics

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 + Atorvastatin 80 mg Placebo (for alirocumab) SC injection Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Alirocumab + Atorvastatin 10 mg Alirocumab 150 mg SC injection Q2W in combination with atorvastatin 10 mg orally once daily for 8 weeks.
Alirocumab + Atorvastatin 80 mg Alirocumab 150 mg SC injection Q2W in combination with atorvastatin 80 mg orally once daily for 8 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo + Atorvastatin 80 mg     Alirocumab + Atorvastatin 10 mg     Alirocumab + Atorvastatin 80 mg     Total  
Number of Participants  
[units: participants]
  31     31     30     92  
Age  
[units: years]
Mean (Standard Deviation)
  55.3  (10.3)     57.9  (10.0)     57.6  (9.3)     56.9  (9.8)  
Gender  
[units: participants]
       
Female     18     17     20     55  
Male     13     14     10     37  
Low-Density Lipoprotein Cholesterol (LDL-C) in mmol/L  
[units: mmol/L]
Mean (Standard Deviation)
  3.138  (0.469)     3.101  (0.402)     3.288  (0.564)     3.174  (0.484)  
LDL-C in mg/dL  
[units: mg/dL]
Mean (Standard Deviation)
  121.2  (18.1)     119.7  (15.5)     126.9  (21.8)     122.6  (18.7)  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent Change From Baseline in Calculated LDL-C at Week 8 - On-treatment Analysis   [ Time Frame: From Baseline to Week 8 (LOCF) ]

2.  Secondary:   Absolute Change From Baseline in Calculated LDL-C (mmol/L) at Week 8 - On-treatment Analysis   [ Time Frame: From baseline to Week 8 (LOCF) ]

3.  Secondary:   Absolute Change From Baseline in Calculated LDL-C (mg/dL) at Week 8 - On-treatment Analysis   [ Time Frame: From baseline to Week 8 (LOCF) ]

4.  Secondary:   Percentage of Participants Achieving Calculated LDL-C <100 mg/dL (2.59 mmol/L) and < 70 mg/dL (1.81 mmol/L) at Week 8 - On-treatment Analysis   [ Time Frame: Week 8 (LOCF) ]

5.  Secondary:   Percent Change From Baseline in Total Cholesterol, Fasting Triglycerides, Non-high-Density Lipoprotein Cholesterol (Non-HDL-C), Apolipoprotein B (Apo-B) and Lipoprotein(a) at Week 8 - On-treatment Analysis   [ Time Frame: From baseline to Week 8 (LOCF) ]

6.  Secondary:   Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 8 - On-treatment Analysis   [ Time Frame: From Baseline to Week 8 (LOCF) ]

7.  Secondary:   Absolute Change in the Ratio Apolipoprotein B/Apolipoprotein A-1 (ApoB/ApoA-1) From Baseline to Week 8 - On-treatment Analysis   [ Time Frame: From Baseline to Week 8 (LOCF) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information
  Hide More Information

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: NCT01288469     History of Changes
Other Study ID Numbers: DFI11566
U1111-1117-9994 ( Other Identifier: UTN )
Study First Received: February 1, 2011
Results First Received: August 21, 2015
Last Updated: August 21, 2015
Health Authority: United States: Food and Drug Administration