Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 (MENDEL-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01763827
First received: January 7, 2013
Last updated: November 25, 2015
Last verified: November 2015
Results First Received: August 28, 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
Biological: Placebo to Evolocumab
Other: Placebo to Ezetimibe

  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
Men and women ≥ 18 to ≤ 80 years of age with fasting low-density lipoprotein cholesterol (LDL-C) ≥ 100 mg/dL and < 190 mg/dL and fasting triglycerides ≤ 400 mg/dL with a 10-year Framingham Risk Score of 10% or less were eligible for this study. The first participant was enrolled on 21 January 2013 and the last participant was enrolled 29 July 2013.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants received subcutaneous placebo corresponding to the once monthly dose volume during a 6 week screening period. Participants who completed the screening period and met final eligibility criteria were randomized 1:1:1:1:2:2 into 6 treatment groups. Randomization was stratified by LDL-C concentration (< 130 mg/dL or ≥ 30 mg/dL).

Reporting Groups
  Description
Placebo Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Placebo QM Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Ezetimibe (Q2W) Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Ezetimibe (QM) Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

Participant Flow:   Overall Study
    Placebo Q2W   Placebo QM   Ezetimibe (Q2W)   Ezetimibe (QM)   Evolocumab Q2W   Evolocumab QM
STARTED   77   78   77   77   153   153 
Received at Least 1 Dose of Study Drug   76   78   77   77   153   153 
COMPLETED   74   77   73   76   147   151 
NOT COMPLETED   3   1   4   1   6   2 
Withdrawal by Subject                1                0                0                0                2                0 
Decision by sponsor                2                0                3                0                2                1 
Lost to Follow-up                0                1                1                1                2                1 



  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 Q2W Participants received placebo subcutaneous injection once every 2 weeks (Q2W) and placebo tablets once a day for up to 12 weeks.
Placebo QM Participants received placebo subcutaneous injection once every month (QM) and placebo tablets once a day for up to 12 weeks.
Ezetimibe (Q2W) Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Ezetimibe (QM) Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Evolocumab Q2W Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Evolocumab QM Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.
Total Total of all reporting groups

Baseline Measures
   Placebo Q2W   Placebo QM   Ezetimibe (Q2W)   Ezetimibe (QM)   Evolocumab Q2W   Evolocumab QM   Total 
Overall Participants Analyzed 
[Units: Participants]
 77   78   77   77   153   153   615 
Age 
[Units: Years]
Mean (Standard Deviation)
 54.4  (10.3)   52.6  (10.7)   53.9  (11.3)   53.0  (12.7)   52.5  (13.7)   52.9  (12.1)   53.1  (12.1) 
Gender 
[Units: Participants]
             
Female   49   47   53   52   104   101   406 
Male   28   31   24   25   49   52   209 
Race/Ethnicity, Customized 
[Units: Participants]
             
American Indian or Alaska Native   0   0   0   1   0   2   3 
Asian   9   8   7   10   12   12   58 
Black or African American   4   6   6   6   9   9   40 
Native Hawaiian or Other Pacific Islander   0   1   0   0   0   0   1 
White   64   63   63   60   132   129   511 
Other   0   0   0   0   0   0   0 
Mixed Race   0   0   1   0   0   1   2 
Race/Ethnicity, Customized 
[Units: Participants]
             
Hispanic or Latino   6   8   9   11   14   21   69 
Not Hispanic or Latino   71   70   68   66   139   132   546 
Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C) 
[Units: Participants]
             
< 130 mg/dL   23   24   22   22   45   45   181 
≥ 130 mg/dL   54   54   55   55   108   108   434 
LDL-C Concentration [1] 
[Units: mg/dL]
Mean (Standard Deviation)
 139.5  (21.3)   144.3  (23.9)   143.3  (23.8)   143.5  (23.1)   141.7  (22.3)   144.4  (23.3)   142.9  (22.9) 
[1] Data are provided for the full analysis set (all randomized participants who received at least 1 dose of investigational product (subcutaneously or orally).
Non-High-Density Lipoprotein Cholesterol (Non-HDL-C) Concentration [1] 
[Units: mg/dL]
Mean (Standard Deviation)
 167.4  (25.8)   172.8  (31.0)   168.8  (28.9)   169.4  (27.3)   166.5  (25.6)   170.4  (26.6)   169.0  (27.2) 
[1] Data are provided for the full analysis set
Apolipoprotein B Concentration [1] 
[Units: mg/dL]
Mean (Standard Deviation)
 103.7  (16.8)   107.3  (19.9)   107.2  (19.7)   106.2  (17.8)   104.5  (17.2)   108.3  (17.9)   106.2  (18.1) 
[1] Data are provided for the full analysis set
Total Cholesterol/High-density Lipoprotein Cholesterol Ratio [1] 
[Units: Ratio]
Mean (Standard Deviation)
 4.148  (1.311)   4.444  (1.465)   4.055  (1.082)   4.335  (1.118)   4.170  (1.170)   4.175  (1.071)   4.210  (1.191) 
[1] Data are provided for the full analysis set
Apolipoprotein B/Apolipoprotein A-1 Ratio [1] 
[Units: Ratio]
Mean (Standard Deviation)
 0.671  (0.193)   0.713  (0.194)   0.691  (0.187)   0.712  (0.173)   0.687  (0.169)   0.707  (0.170)   0.697  (0.178) 
[1] Data are provided for the full analysis set
Lipoprotein(a) [1] 
[Units: nmol/L]
Median (Inter-Quartile Range)
 21.0 
 (9.0 to 49.0) 
 21.5 
 (7.0 to 62.0) 
 28.0 
 (11.0 to 120.0) 
 28.0 
 (12.0 to 64.0) 
 20.0 
 (7.0 to 58.0) 
 28.0 
 (9.0 to 104.0) 
 25.0 
 (9.0 to 71.0) 
[1] Data are provided for the full analysis set
Triglycerides [1] 
[Units: mg/dL]
Median (Inter-Quartile Range)
 113.5 
 (83.3 to 178.0) 
 118.0 
 (85.5 to 178.5) 
 112.5 
 (83.5 to 158.0) 
 116.5 
 (90.0 to 159.0) 
 112.0 
 (81.5 to 147.5) 
 119.0 
 (82.5 to 168.5) 
 115.3 
 (83.5 to 163.0) 
[1] Data are provided for the full analysis set
Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration [1] 
[Units: mg/dL]
Median (Inter-Quartile Range)
 22.5 
 (16.8 to 34.3) 
 23.8 
 (17.0 to 35.5) 
 22.5 
 (16.5 to 32.0) 
 23.5 
 (18.0 to 31.5) 
 22.5 
 (16.5 to 29.5) 
 23.5 
 (16.5 to 33.5) 
 23.0 
 (16.5 to 32.5) 
[1] Data are provided for the full analysis set
High-density Lipoprotein Cholesterol (HDL-C) Concentration [1] 
[Units: mg/dL]
Median (Inter-Quartile Range)
 57.0 
 (43.8 to 77.3) 
 54.0 
 (44.5 to 65.5) 
 58.5 
 (47.0 to 69.5) 
 53.5 
 (42.0 to 67.5) 
 53.0 
 (44.5 to 67.0) 
 56.5 
 (46.5 to 65.5) 
 55.3 
 (44.5 to 67.5) 
[1] Data are provided for the full analysis set


  Outcome Measures
  Show All Outcome Measures

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

2.  Primary:   Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

3.  Secondary:   Change From Baseline in LDL-C at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

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

5.  Secondary:   Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL   [ Time Frame: Weeks 10 and 12 ]

6.  Secondary:   Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12   [ Time Frame: Week 12 ]

7.  Secondary:   Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

8.  Secondary:   Percent Change From Baseline in Non-HDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]

9.  Secondary:   Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

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

11.  Secondary:   Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

12.  Secondary:   Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-cholesterol Ratio at Week 12   [ Time Frame: Baseline and Week 12 ]

13.  Secondary:   Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

14.  Secondary:   Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12   [ Time Frame: Baseline and Week 12 ]

15.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

16.  Secondary:   Percent Change From Baseline in Lipoprotein (a) at Week 12   [ Time Frame: Baseline and Week 12 ]

17.  Secondary:   Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

18.  Secondary:   Percent Change From Baseline in Triglycerides at Week 12   [ Time Frame: Baseline and Week 12 ]

19.  Secondary:   Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

20.  Secondary:   Percent Change From Baseline in VLDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]

21.  Secondary:   Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12   [ Time Frame: Baseline and Weeks 10 and 12 ]

22.  Secondary:   Percent Change From Baseline in HDL-C at Week 12   [ Time Frame: Baseline and Week 12 ]


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


Publications:

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01763827     History of Changes
Other Study ID Numbers: 20110114
Study First Received: January 7, 2013
Results First Received: August 28, 2015
Last Updated: November 25, 2015
Health Authority: Brazil: National Health Surveillance Agency
South Korea: Korea Food and Drug Administration (KFDA)
Australia: Department of Health and Ageing Therapeutic Goods Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Health and Medicines Authority
South Africa: Medicines Control Council
Turkey: Ministry of Health
Canada: Health Canada
United States: Food and Drug Administration
Taiwan: Taiwan Food and Drug Administration