Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects (GAUSS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01375764
First received: June 16, 2011
Last updated: November 19, 2015
Last verified: November 2015
Results First Received: September 2, 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

The study enrolled adults aged 18 to 75 years with hypercholesterolemia who were statin intolerant and with low-density lipoprotein cholesterol (LDL-C) levels above risk-based goals recommended by the National Cholesterol Education Program.

The first patient enrolled on 28 July 2011; last patient enrolled 14 February 2012.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomization was stratified by screening LDL-C level (< 130 mg/dL [3.4 mmol/L] or ≥ 130 mg/dL) and statin use at baseline (yes or no).

Reporting Groups
  Description
Ezetimibe Participants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab + Ezetimibe Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab 280 mg Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mg Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.

Participant Flow:   Overall Study
    Ezetimibe     Evolocumab + Ezetimibe     Evolocumab 280 mg     Evolocumab 350 mg     Evolocumab 420 mg  
STARTED     33     31     32     32     32  
Received Treatment     32     30     32     31     32  
COMPLETED     31     30     32     31     31  
NOT COMPLETED     2     1     0     1     1  
Lost to Follow-up                 0                 1                 0                 0                 0  
Withdrawal by Subject                 2                 0                 0                 0                 1  
Other                 0                 0                 0                 1                 0  



  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
Ezetimibe Participants received placebo subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab + Ezetimibe Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks and 10 mg ezetimibe orally once a day for 12 weeks.
Evolocumab 280 mg Participants received 280 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 350 mg Participants received 350 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Evolocumab 420 mg Participants received 420 mg evolocumab by subcutaneous injection once every 4 weeks for 12 weeks.
Total Total of all reporting groups

Baseline Measures
    Ezetimibe     Evolocumab + Ezetimibe     Evolocumab 280 mg     Evolocumab 350 mg     Evolocumab 420 mg     Total  
Number of Participants  
[units: participants]
  32     30     32     31     32     157  
Age  
[units: years]
Mean (Standard Deviation)
  62.4  (6.6)     62.0  (7.2)     62.2  (10.1)     62.3  (9.1)     60.0  (8.6)     61.8  (8.4)  
Gender  
[units: participants]
           
Female     18     23     18     21     20     100  
Male     14     7     14     10     12     57  
Race/Ethnicity, Customized  
[units: participants]
           
American Indian or Alaska Native     0     0     0     0     0     0  
Asian     2     5     1     0     0     8  
Black or African American     2     1     2     2     1     8  
Native Hawaiian or Other Pacific Islander     0     0     0     0     1     1  
White     28     24     28     29     30     139  
Other     0     0     1     0     0     1  
Race/Ethnicity, Customized  
[units: participants]
           
Hispanic or Latino     2     0     0     0     0     2  
Not Hispanic or Latino     30     30     32     31     32     155  
Stratification Factor: LDL-C Level  
[units: participants]
           
< 130 mg/dL     2     1     2     2     2     9  
≥ 130 mg/dL     30     29     30     29     30     148  
Stratification Factor: Baseline Use of Statin  
[units: participants]
           
No     26     26     27     27     27     133  
Yes     6     4     5     4     5     24  
LDL-C Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  182.9  (36.4)     194.4  (60.1)     194.8  (48.1)     190.3  (47.8)     203.5  (60.3)     193.2  (51.0)  
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  213.7  (40.4)     219.8  (60.5)     225.5  (53.3)     222.9  (55.8)     240.6  (63.9)     224.6  (55.3)  
Apolipoprotein B Concentration  
[units: mg/dL]
Mean (Standard Deviation)
  138.0  (21.7)     138.8  (33.1)     143.0  (30.6)     144.9  (33.9)     150.8  (34.1)     143.2  (30.9)  
Total Cholesterol/HDL-C Ratio  
[units: ratio]
Mean (Standard Deviation)
  4.907  (1.553)     5.093  (2.416)     5.287  (1.816)     5.444  (2.308)     6.438  (2.834)     5.438  (2.265)  
Apolipoprotein B/Apolipoprotein A-1 Ratio  
[units: ratio]
Mean (Standard Deviation)
  0.841  (0.230)     0.882  (0.332)     0.906  (0.265)     0.916  (0.332)     1.055  (0.388)     0.921  (0.319)  



  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.  Primary:   Percent Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe   [ Time Frame: Baseline and Week 12 ]

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

4.  Secondary:   Change From Baseline in LDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe   [ Time Frame: Baseline and Week 12 ]

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

6.  Secondary:   Percent Change From Baseline in Non-HDL-C at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe   [ Time Frame: Baseline and Week 12 ]

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

8.  Secondary:   Percent Change From Baseline in Apolipoprotein B at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe   [ Time Frame: Baseline and Week 12 ]

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

10.  Secondary:   Percent Change From Baseline in Total Cholesterol/HDL-C Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe   [ Time Frame: Baseline and Week 12 ]

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

12.  Secondary:   Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12: Ezetimibe Alone Versus Evolocumab + Ezetimibe   [ 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: NCT01375764     History of Changes
Other Study ID Numbers: 20090159
Study First Received: June 16, 2011
Results First Received: September 2, 2015
Last Updated: November 19, 2015
Health Authority: Australia: Therapeutic Goods Administration
Belgium: Directorate-General for Medicinal Products
Canada: Health Canada
Denmark: Laegemiddelstyrelsen
Finland: Lääkelaitos
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
United States: Food and Drug Administration