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Effects on Lipoprotein Metabolism From PCSK9 Inhibition Utilizing a Monoclonal Antibody (FLOREY)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02189837
Recruitment Status : Completed
First Posted : July 15, 2014
Results First Posted : August 31, 2016
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Primary Hyperlipidemia and Mixed Dyslipidemia
Interventions Biological: Evolocumab
Drug: Atorvastatin
Drug: Placebo to Evolocumab
Drug: Placebo to Atorvastatin
Enrollment 89
Recruitment Details This study was conducted at 2 centers in Australia. The first participant was enrolled on 08 July 2014, and the last participant enrolled on 15 December 2014.
Pre-assignment Details Participants who met eligibility criteria underwent an initial 4 week run-in period of dietary stabilization before randomization. Randomization was stratified based on screening low-density lipoprotein (LDL-C) concentration (< 130 mg/dL vs ≥ 130 mg/dL)
Arm/Group Title Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks. Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Period Title: Overall Study
Started 22 23 23 21
Received Treatment 21 22 22 20
Completed 20 22 20 19
Not Completed 2 1 3 2
Reason Not Completed
Withdrawal by Subject             2             1             3             1
Sponsor Decision             0             0             0             1
Arm/Group Title Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin Total
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks. Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 21 22 22 20 85
Hide Baseline Analysis Population Description
The full analysis set includes all randomized participants who received any study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants 22 participants 22 participants 20 participants 85 participants
33.9  (12.7) 30.4  (7.4) 33.5  (11.6) 31.0  (9.8) 32.2  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 22 participants 22 participants 20 participants 85 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
21
 100.0%
22
 100.0%
22
 100.0%
20
 100.0%
85
 100.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 22 participants 22 participants 20 participants 85 participants
American Indian or Alaska Native 0 0 0 0 0
Asian 1 2 1 3 7
Black or African American 0 0 0 3 3
Native Hawaiian or Other Pacific Islander 0 0 0 0 0
White 19 20 20 14 73
Other 1 0 1 0 2
Mixed Race 0 0 0 0 0
Screening LDL-C Level  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants 22 participants 22 participants 20 participants 85 participants
< 130 mg/dL 9 9 9 8 35
≥ 130 mg/dL 12 13 13 12 50
LDL-C Concentration   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 21 participants 22 participants 22 participants 20 participants 85 participants
118.1  (18.1) 123.2  (21.3) 118.2  (18.4) 116.5  (23.7) 119.1  (20.2)
[1]
Measure Description: LDL-C was measured using ultracentrifugation
1.Primary Outcome
Title Percent Change From Baseline in Low-density Lipoprotein (LDL) Apolipoprotein B-100 Fractional Catabolic Rate (FCR)
Hide Description The fractional catabolic rate (the percentage of apolipoprotein B-100 in LDL which is replaced, transferred or lost per unit of time) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. LDL particles were isolated from plasma by sequential ultracentrifugation, and isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism.
Time Frame Baseline (5 days prior to Day 1) and Day 50; plasma samples for fasting lipids were obtained at 0, 5, 10, 20, 30, 40, and 60 min, as well as at 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours, and 2, 3, 4 and 5 days after D3-leucine administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set including all randomized and dosed participants who completed baseline and Day 50 measurements.
Arm/Group Title Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Overall Number of Participants Analyzed 20 22 20 19
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-5.07  (26.06) 74.13  (24.84) 83.70  (26.06) 310.48  (26.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments The superiority of evolocumab monotherapy to placebo was tested using a 2-sided p-value at a significance level of 0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 88.76
Confidence Interval (2-Sided) 95%
15.73 to 161.80
Parameter Dispersion
Type: Standard Error of the Mean
Value: 36.67
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin, Evolocumab and Atorvastatin
Comments The treatment effect of evolocumab plus atorvastatin compared with placebo plus atorvastatin was estimated and a nominal p-value is provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 236.35
Confidence Interval (2-Sided) 95%
164.02 to 308.69
Parameter Dispersion
Type: Standard Error of the Mean
Value: 36.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atorvastatin, Evolocumab, Evolocumab and Atorvastatin
Comments To assess whether the treatment effect of evolocumab compared with placebo depended on being administered alone or combined with atorvastatin, the interaction was tested, i.e., the difference between the treatment difference versus the respective placebo group for the evolocumab+atorvastatin group and the evolocumab group was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter Treatment Effect
Estimated Value 147.59
Confidence Interval (2-Sided) 95%
44.80 to 250.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 51.61
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline in LDL-C at Day 50
Hide Description LDL-C was measured using ultrcentrifugation.
Time Frame Baseline and Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set with available data at both time points
Arm/Group Title Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Overall Number of Participants Analyzed 19 22 18 17
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-0.65  (3.09) -45.25  (2.86) -57.79  (3.15) -83.19  (3.24)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -57.14
Confidence Interval 95%
-65.91 to -48.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin, Evolocumab and Atorvastatin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -37.95
Confidence Interval (2-Sided) 95%
-46.55 to -29.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atorvastatin, Evolocumab, Evolocumab and Atorvastatin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter Treatment Effect
Estimated Value 19.20
Confidence Interval (2-Sided) 95%
6.93 to 31.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.15
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in LDL Apolipoprotein B-100 Production Rate (PR)
Hide Description The production rate of apolipoprotein B-100 in LDL was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. LDL particles were isolated from plasma by sequential ultracentrifugation and isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate the production rate.
Time Frame Baseline and Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set
Arm/Group Title Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Overall Number of Participants Analyzed 20 22 20 19
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-3.80  (7.40) -3.27  (7.05) -20.45  (7.40) -35.93  (7.57)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -16.65
Confidence Interval (2-Sided) 95%
-37.37 to 4.08
Parameter Dispersion
Type: Standard Error of the Mean
Value: 10.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin, Evolocumab and Atorvastatin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -32.66
Confidence Interval (2-Sided) 95%
-53.19 to -12.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 10.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atorvastatin, Evolocumab, Evolocumab and Atorvastatin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter Treatment Effect
Estimated Value -16.01
Confidence Interval (2-Sided) 95%
-45.18 to 13.16
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.65
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein (a) Fractional Catabolic Rate (FCR)
Hide Description The fractional catabolic rate (the percentage of lipoprotein(a) (Lp[a]) which is replaced, transferred or lost per unit of time) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. Lp(a) was isolated from plasma using an immunoprecipitation method employing immunomagnetic beads and polyacrylamide gel electrophoresis. Isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism.
Time Frame Baseline (5 days prior to Day 1) and Day 50; plasma samples for fasting lipids were obtained at 0, 5, 10, 20, 30, 40, and 60 min, as well as at 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 10 hours, and 2, 3, 4 and 5 days after D3-leucine administration.
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set with available data
Arm/Group Title Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Overall Number of Participants Analyzed 16 17 14 16
Least Squares Mean (Standard Error)
Unit of Measure: percent change
7.49  (9.17) 25.52  (8.92) 5.37  (9.81) 64.57  (9.23)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments The superiority of evolocumab monotherapy to placebo was tested using a 2-sided p-value at a significance level of 0.05.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.87
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -2.12
Confidence Interval (2-Sided) 95%
-28.94 to 24.70
Parameter Dispersion
Type: Standard Error of the Mean
Value: 13.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin, Evolocumab and Atorvastatin
Comments The treatment effect of evolocumab plus atorvastatin compared with placebo plus atorvastatin was estimated and a nominal p-value is provided.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 39.06
Confidence Interval (2-Sided) 95%
13.52 to 64.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 12.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atorvastatin, Evolocumab, Evolocumab and Atorvastatin
Comments To assess whether the treatment effect of evolocumab compared with placebo depended on being administered alone or combined with atorvastatin, the interaction was tested, i.e., the difference between the treatment difference versus the respective placebo group for the evolocumab+atorvastatin group and the evolocumab group was calculated.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter Treatment Effect
Estimated Value 41.18
Confidence Interval (2-Sided) 95%
4.15 to 78.20
Parameter Dispersion
Type: Standard Error of the Mean
Value: 18.50
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline in Lipoprotein(a) Production Rate (PR)
Hide Description The production rate of lipoprotein(a) was measured at Baseline and Day 50 over 5 consecutive days using the stable isotope tracer, D3-leucine. Lp(a) was isolated from plasma using an immunoprecipitation method employing immunomagnetic beads and polyacrylamide gel electrophoresis. Isotopic enrichment was determined using gas chromatography-mass spectrometry. Mathematical modelling of the protein enrichment data was used to estimate protein catabolism.
Time Frame Baseline and Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy Analysis Set with available data
Arm/Group Title Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Hide Arm/Group Description:
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks.
Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
Overall Number of Participants Analyzed 16 17 14 16
Least Squares Mean (Standard Error)
Unit of Measure: percent change
3.52  (7.94) -6.88  (7.72) -35.91  (8.49) 16.40  (7.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Evolocumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value -39.43
Confidence Interval (2-Sided) 95%
-62.66 to -16.21
Parameter Dispersion
Type: Standard Error of the Mean
Value: 11.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin, Evolocumab and Atorvastatin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter LS Mean Treatment Difference
Estimated Value 23.28
Confidence Interval (2-Sided) 95%
1.16 to 45.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 11.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Atorvastatin, Evolocumab, Evolocumab and Atorvastatin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Model includes terms for the 2 factors in the factorial design (placebo or evolocumab and oral placebo or statin), their interaction, and LDL-C level.
Method of Estimation Estimation Parameter Treatment Effect
Estimated Value 62.72
Confidence Interval (2-Sided) 95%
30.65 to 94.79
Parameter Dispersion
Type: Standard Error of the Mean
Value: 16.02
Estimation Comments [Not Specified]
Time Frame From first dose of study drug until day 73
Adverse Event Reporting Description Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
 
Arm/Group Title Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Hide Arm/Group Description Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks. Participants received placebo subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and placebo tablets once a day for up to 8 weeks. Participants received 420 mg evolocumab by subcutaneous injection once every 2 weeks on days 1, 15, 29 and 43 and 80 mg atorvastatin orally once a day for up to 8 weeks.
All-Cause Mortality
Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/21 (0.00%)   0/22 (0.00%)   0/22 (0.00%)   1/20 (5.00%) 
Hepatobiliary disorders         
Liver injury  1  0/21 (0.00%)  0/22 (0.00%)  0/22 (0.00%)  1/20 (5.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Atorvastatin Evolocumab Evolocumab and Atorvastatin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/21 (23.81%)   12/22 (54.55%)   14/22 (63.64%)   10/20 (50.00%) 
Gastrointestinal disorders         
Abdominal pain  1  0/21 (0.00%)  2/22 (9.09%)  0/22 (0.00%)  1/20 (5.00%) 
Nausea  1  1/21 (4.76%)  3/22 (13.64%)  2/22 (9.09%)  2/20 (10.00%) 
General disorders         
Influenza like illness  1  0/21 (0.00%)  0/22 (0.00%)  2/22 (9.09%)  0/20 (0.00%) 
Infections and infestations         
Nasopharyngitis  1  1/21 (4.76%)  1/22 (4.55%)  2/22 (9.09%)  0/20 (0.00%) 
Pharyngitis  1  0/21 (0.00%)  2/22 (9.09%)  1/22 (4.55%)  0/20 (0.00%) 
Upper respiratory tract infection  1  0/21 (0.00%)  2/22 (9.09%)  0/22 (0.00%)  1/20 (5.00%) 
Investigations         
Blood creatine phosphokinase increased  1  0/21 (0.00%)  2/22 (9.09%)  0/22 (0.00%)  1/20 (5.00%) 
Musculoskeletal and connective tissue disorders         
Myalgia  1  1/21 (4.76%)  1/22 (4.55%)  0/22 (0.00%)  2/20 (10.00%) 
Neck pain  1  0/21 (0.00%)  2/22 (9.09%)  1/22 (4.55%)  0/20 (0.00%) 
Nervous system disorders         
Headache  1  2/21 (9.52%)  5/22 (22.73%)  8/22 (36.36%)  7/20 (35.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.1
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 Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02189837    
Other Study ID Numbers: 20130194
FLOREY ( Other Identifier: Amgen )
First Submitted: July 8, 2014
First Posted: July 15, 2014
Results First Submitted: June 6, 2016
Results First Posted: August 31, 2016
Last Update Posted: October 3, 2018