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Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2 (GAUSS-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01763905
First received: January 7, 2013
Last updated: November 18, 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: Placebo to Evolocumab
Drug: Ezetimibe
Drug: Placebo to Ezetimibe

  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

Men and women ≥ 18 to ≤ 80 years of age who have tried at least 2 statins and were unable to tolerate any dose or increase in statin dose due to muscle-related side effects were eligible for this study.

The first participant was enrolled on 24 January 2013 and the last participant enrolled on 29 August 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. Those who completed the screening period and met final eligibility criteria were randomized 1:1:2:2 into 4 treatment groups. Randomization was stratified by low-density lipoprotein cholesterol (LDL-C) level and statin use.

Reporting Groups
  Description
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
    Ezetimibe (Q2W)   Ezetimibe (QM)   Evolocumab Q2W   Evolocumab QM
STARTED   51   51   103   102 
COMPLETED   45   50   94   101 
NOT COMPLETED   6   1   9   1 
Withdrawal by Subject                1                1                0                1 
Decision by sponsor                5                0                8                0 
Lost to Follow-up                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.
No text entered.

Reporting Groups
  Description
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
   Ezetimibe (Q2W)   Ezetimibe (QM)   Evolocumab Q2W   Evolocumab QM   Total 
Overall Participants Analyzed 
[Units: Participants]
 51   51   103   102   307 
Age 
[Units: Years]
Mean (Standard Deviation)
 61.7  (10.1)   60.2  (8.7)   60.5  (9.7)   62.9  (10.2)   61.5  (9.8) 
Gender 
[Units: Participants]
         
Female   27   22   46   46   141 
Male   24   29   57   56   166 
Race/Ethnicity, Customized 
[Units: Participants]
         
American Indian or Alaska Native   0   0   0   0   0 
Asian   1   3   5   1   10 
Black or African American   0   1   3   3   7 
Native Hawaiian or Other Pacific Islander   0   0   1   0   1 
White   49   46   94   98   287 
Other   1   1   0   0   2 
Race/Ethnicity, Customized 
[Units: Participants]
         
Hispanic or Latino   1   2   3   1   7 
Not Hispanic or Latino   50   49   100   101   300 
Stratification Factor: Low-density Lipoprotein Cholesterol (LDL-C) Level 
[Units: Participants]
         
< 180 mg/dL   26   26   52   52   156 
≥ 180 mg/dL   25   25   51   50   151 
Stratification Factor: Baseline Statin Use 
[Units: Participants]
         
No   41   42   84   82   249 
Yes   10   9   19   20   58 
LDL-C Concentration 
[Units: mg/dL]
Mean (Standard Deviation)
 194.7  (63.8)   195.2  (51.8)   192.0  (57.0)   192.2  (61.2)   193.1  (58.5) 
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration 
[Units: mg/dL]
Mean (Standard Deviation)
 231.4  (66.0)   232.9  (57.0)   227.9  (56.6)   222.1  (63.2)   227.4  (60.4) 
Apolipoprotein B Concentration 
[Units: mg/dL]
Mean (Standard Deviation)
 140.0  (37.0)   140.0  (31.1)   140.2  (32.1)   133.1  (32.2)   137.8  (32.8) 
Total Cholesterol/High-Density Lipoprotein Cholesterol Ratio 
[Units: Ratio]
Mean (Standard Deviation)
 5.989  (2.190)   6.137  (1.787)   5.912  (1.929)   5.506  (1.925)   5.827  (1.956) 
Apolipoprotein B/Apolipoprotein A1 Ratio 
[Units: Ratio]
Mean (Standard Deviation)
 0.943  (0.282)   1.005  (0.294)   0.980  (0.318)   0.901  (0.283)   0.952  (0.298) 
Lipoprotein(a) Concentration 
[Units: nmol/L]
Mean (Standard Deviation)
 106.3  (101.0)   76.6  (96.7)   66.2  (72.5)   70.9  (99.9)   76.2  (91.9) 
Triglyceride Concentration 
[Units: mg/dL]
Mean (Standard Deviation)
 183.4  (79.8)   187.0  (81.5)   179.8  (80.0)   149.3  (63.1)   171.5  (76.3) 
Very Low-density Lipoprotein Cholesterol (VLDL-C) Concentration 
[Units: mg/dL]
Mean (Standard Deviation)
 36.7  (16.0)   37.1  (15.8)   35.2  (14.5)   29.9  (12.6)   34.0  (14.6) 
High-Density Lipoprotein Cholesterol (HDL-C) 
[Units: mg/dL]
Mean (Standard Deviation)
 52.4  (18.3)   48.0  (11.0)   51.1  (16.4)   54.0  (16.0)   51.8  (15.9) 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent Change From Baseline in 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 With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)   [ Time Frame: Weeks 10 and 12 ]

6.  Secondary:   Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12   [ Time Frame: Week 12 ]

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

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

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

22.  Secondary:   Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol 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: NCT01763905     History of Changes
Other Study ID Numbers: 20110116
2012-001364-30 ( EudraCT Number )
Study First Received: January 7, 2013
Results First Received: September 2, 2015
Last Updated: November 18, 2015
Health Authority: Hong Kong: Department of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Australia: Department of Health and Ageing Therapeutic Goods Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Spain: Agencia Española de Medicamentos y Productos Sanitarios
South Africa: Medicines Control Council
Switzerland: Swissmedic
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Health and Medicines Authority
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
United States: Food and Drug Administration