LAPLACE-TIMI 57: Low-density Lipoprotein Cholesterol (LDL-C) Assessment With PCSK9 monoclonaL Antibody Inhibition Combined With Statin thErapy (LAPLACE)

This study has been completed.
Sponsor:
Collaborator:
TIMI Study Group
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01380730
First received: June 23, 2011
Last updated: September 1, 2015
Last verified: August 2015
Results First Received: September 1, 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
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 aged 18 - 80 years who were on a statin, with or without ezetimibe, with stable dose(s) for at least 4 weeks, and fasting low-density lipoprotein cholesterol (LDL-C) ≥ 85 mg/dL.

The first patient enrolled on 18 July 2011 and the last patient enrolled on 22 December 2011.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible participants were randomized equally into 1 of 8 treatment groups. Randomization was stratified by screening LDL-C level (< 130 mg/dL or ≥ 130 mg/dL) and ezetimibe use at baseline (yes or no).

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.
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     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     78     79     79     79     78     79     79     80  
Received Treatment     78     77 [1]   79     79     78     79     79     80  
COMPLETED     78     79     79     79     77     79     79     80  
NOT COMPLETED     0     0     0     0     1     0     0     0  
Death                 0                 0                 0                 0                 1                 0                 0                 0  
[1] 2 participants did not receive treatment but were followed until the end of study



  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.
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     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]
  78     77     79     79     78     79     79     80     629  
Age  
[units: years]
Mean (Standard Deviation)
  60.2  (8.8)     60.1  (9.6)     59.4  (9.9)     58.8  (9.7)     62.4  (10.2)     60.3  (8.4)     61.9  (8.8)     60.9  (10.3)     60.5  (9.5)  
Gender  
[units: participants]
                 
Female     42     41     44     25     45     40     38     44     319  
Male     36     36     35     54     33     39     41     36     310  
Race/Ethnicity, Customized  
[units: participants]
                 
American Indian or Alaska Native     0     1     0     0     1     1     0     0     3  
Asian     0     2     1     3     1     2     2     1     12  
Black or African American     6     0     6     8     9     8     4     9     50  
Native Hawaiian or Other Pacific Islander     0     0     0     1     0     2     0     0     3  
White     72     74     72     67     67     64     72     70     558  
Other     0     0     0     0     0     2     1     0     3  
Race/Ethnicity, Customized  
[units: participants]
                 
Hispanic or Latino     1     6     5     0     6     1     0     2     21  
Not Hispanic or Latino     77     71     74     79     72     78     79     78     608  
Stratification Factor: LDL-C Level  
[units: participants]
                 
< 130 mg/dL     51     51     51     51     52     51     52     53     412  
≥ 130 mg/dL     27     26     28     28     26     28     27     27     217  
Stratification Factor: Baseline Ezetimibe Use  
[units: participants]
                 
No     71     69     72     72     71     72     72     73     572  
Yes     7     8     7     7     7     7     7     7     57  
LDL-C Concentration [1]
[units: mg/dL]
Mean (Standard Deviation)
  122.2  (27.1)     124.9  (30.6)     121.4  (24.4)     127.4  (32.1)     120.9  (25.1)     122.0  (28.8)     123.2  (27.1)     120.8  (26.5)     122.8  (27.7)  
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  146.9  (29.9)     150.2  (36.5)     145.3  (29.9)     151.2  (37.2)     145.3  (26.2)     146.3  (33.3)     150.0  (29.1)     144.4  (31.2)     147.4  (31.8)  
Apolipoprotein B Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  99.9  (17.0)     101.6  (20.0)     99.9  (16.8)     103.6  (22.3)     98.8  (16.6)     101.3  (21.2)     102.6  (18.9)     99.9  (18.6)     100.9  (19.0)  
Total Cholesterol/HDL-C ratio  
[units: ratio]
Mean (Standard Deviation)
  3.940  (1.016)     4.057  (1.303)     4.002  (1.243)     4.128  (1.473)     3.932  (1.022)     4.007  (1.300)     4.118  (0.963)     3.885  (1.090)     4.008  (1.184)  
Apolipoprotein B/Apolipoprotein A-1 Ratio  
[units: ratio]
Mean (Standard Deviation)
  0.660  (0.155)     0.676  (0.194)     0.675  (0.191)     0.695  (0.219)     0.649  (0.155)     0.662  (0.199)     0.687  (0.175)     0.653  (0.177)     0.670  (0.184)  
[1] LDL-C was measured using ultracentrifugation.



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

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01380730     History of Changes
Other Study ID Numbers: 20101155
Study First Received: June 23, 2011
Results First Received: September 1, 2015
Last Updated: September 1, 2015
Health Authority: Canada: Health Canada
Czech Republic: Statni ustav pro kontrolu leciv
Denmark: Laegemiddelstyrelsen
Hungary: National Institute of Pharmacy
United States: Food and Drug Administration