Monoclonal Antibody Against PCSK9 to Reduce Elevated Low-density Lipoprotein Cholesterol (LDL-C) in Adults Currently Not Receiving Drug Therapy for Easing Lipid Levels (MENDEL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01375777
First received: June 16, 2011
Last updated: September 3, 2015
Last verified: September 2015
Results First Received: September 3, 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: Hyperlipidemia
Interventions: Biological: Evolocumab
Drug: Ezetimibe
Other: Placebo to Evolocumab

  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
This study enrolled adults 18 - 75 years with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL, fasting triglycerides ≤ 400 mg/dL and a National Cholesterol Education Program Adult Treatment Panel III Framingham risk score of 10% or less. First patient enrolled 06 July 2011, last patient enrolled 25 November 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized with equal allocation into 1 of 9 treatment groups. Randomization was stratified on the basis of screening LDL-C concentration (< 130 mg/dL [3.4 mmol/L] or ≥ 130 mg/dL).

Reporting Groups
  Description
Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Placebo Q4W Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Ezetimibe Participants received 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab 70 mg Q2W Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 105 mg Q2W Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 140 mg Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 280 mg Q4W Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mg Q4W Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Q4W Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Participant Flow:   Overall Study
    Placebo Q2W     Placebo Q4W     Ezetimibe     Evolocumab 70 mg Q2W     Evolocumab 105 mg Q2W     Evolocumab 140 mg Q2W     Evolocumab 280 mg Q4W     Evolocumab 350 mg Q4W     Evolocumab 420 mg Q4W  
STARTED     46     45     46     45     46     45     46     46     46  
Received Treatment     45     45     45     45     46     45     45     45     45  
COMPLETED     44     42     45     45     45     44     44     44     44  
NOT COMPLETED     2     3     1     0     1     1     2     2     2  
Withdrawal by Subject                 0                 2                 1                 0                 1                 1                 1                 2                 1  
Lost to Follow-up                 1                 0                 0                 0                 0                 0                 1                 0                 0  
Other                 1                 1                 0                 0                 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.
Full analysis set (all randomized participants who received at least 1 dose of investigational product).

Reporting Groups
  Description
Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks.
Placebo Q4W Participants received placebo subcutaneous injection once every 4 weeks (Q4W) for 12 weeks.
Ezetimibe Participants received 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab 70 mg Q2W Participants received 70 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 105 mg Q2W Participants received 105 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 140 mg Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks.
Evolocumab 280 mg Q4W Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mg Q4W Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Q4W Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Total Total of all reporting groups

Baseline Measures
    Placebo Q2W     Placebo Q4W     Ezetimibe     Evolocumab 70 mg Q2W     Evolocumab 105 mg Q2W     Evolocumab 140 mg Q2W     Evolocumab 280 mg Q4W     Evolocumab 350 mg Q4W     Evolocumab 420 mg Q4W     Total  
Number of Participants  
[units: participants]
  45     45     45     45     46     45     45     45     45     406  
Age  
[units: years]
Mean (Standard Deviation)
  52.5  (9.8)     50.7  (12.6)     50.0  (12.0)     50.9  (12.9)     48.3  (11.8)     52.8  (11.6)     49.3  (10.3)     50.9  (13.1)     50.1  (12.0)     50.6  (11.8)  
Gender  
[units: participants]
                   
Female     25     30     26     30     33     36     28     33     26     267  
Male     20     15     19     15     13     9     17     12     19     139  
Race/Ethnicity, Customized  
[units: participants]
                   
American Indian or Alaska Native     0     0     0     1     0     0     1     1     0     3  
Asian     2     1     1     3     3     2     1     2     2     17  
Black or African American     8     7     9     7     5     4     8     6     10     64  
Native Hawaiian or Other Pacific Islander     0     1     0     0     1     0     0     0     0     2  
White     35     36     35     33     37     39     35     36     33     319  
Other     0     0     0     1     0     0     0     0     0     1  
Race/Ethnicity, Customized  
[units: participants]
                   
Hispanic or Latino     5     6     5     5     5     8     7     5     10     56  
ot Hispanic or Latino     40     39     40     40     41     37     38     40     35     350  
Stratification Factor: LDL-C level  
[units: participants]
                   
< 130 mg/dL     15     14     15     14     15     14     15     15     14     131  
≥ 130 mg/dL     30     31     30     31     31     31     30     30     31     275  
LDL-C Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  147.0  (21.0)     142.3  (24.3)     144.2  (25.8)     143.1  (21.7)     141.5  (22.3)     139.8  (21.1)     141.1  (21.8)     136.6  (20.8)     138.9  (21.9)     141.6  (22.3)  
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  173.8  (30.5)     169.1  (27.7)     170.0  (32.0)     169.0  (24.5)     169.2  (24.3)     163.8  (23.7)     166.3  (27.8)     161.1  (26.1)     167.9  (29.6)     167.8  (27.4)  
Apolipoprotein B Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  111.7  (17.1)     110.4  (17.2)     109.9  (17.7)     108.7  (15.7)     108.5  (15.2)     107.2  (16.3)     109.2  (15.7)     105.8  (15.9)     110.2  (18.4)     109.1  (16.5)  
Total Cholesterol/HDL-C Ratio  
[units: ratio]
Mean (Standard Deviation)
  4.477  (1.293)     4.793  (1.836)     4.670  (1.258)     4.335  (1.090)     4.571  (1.269)     4.181  (1.131)     4.500  (1.154)     4.335  (1.282)     4.741  (1.656)     4.512  (1.351)  
Apolipoprotein B/Apolipoprotein A-1 Ratio  
[units: ratio]
Mean (Standard Deviation)
  0.729  (0.180)     0.785  (0.322)     0.752  (0.176)     0.705  (0.161)     0.744  (0.168)     0.709  (0.175)     0.751  (0.161)     0.706  (0.185)     0.758  (0.191)     0.738  (0.196)  



  Outcome Measures
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1.  Primary:   Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12   [ Time Frame: Baseline and Week 12 ]

2.  Secondary:   Change From Baseline in LDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]

3.  Secondary:   Percent Change From Baseline in Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12   [ Time Frame: Baseline and Week 12 ]

4.  Secondary:   Percent Change From Baseline in Apolipoprotein B at Week 12   [ Time Frame: Baseline and Week 12 ]

5.  Secondary:   Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12   [ Time Frame: Baseline and Week 12 ]

6.  Secondary:   Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12   [ Time Frame: Baseline and Week 12 ]


  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: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications:

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01375777     History of Changes
Other Study ID Numbers: 20101154
Study First Received: June 16, 2011
Results First Received: September 3, 2015
Last Updated: September 3, 2015
Health Authority: Canada: Health Canada
Denmark: Laegemiddelstyrelsen
Germany: Paul_Ehrlich-Institut Bundesamt fur Sera und Impfstoffe
South Africa: Medicines Control Council
United States: Food and Drug Administration
Australia: Therapeutic Goods Administration
Belgium: Directorate-General for Medicinal Products