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Study Overview
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Brief Summary
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This study evaluated change over time in neurocognitive testing in patients receiving statin therapy in combination with evolocumab (AMG 145), compared with patients receiving statin therapy in combination with placebo.

Detailed Description
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Participants who were enrolled in study 20110118 (FOURIER; NCT01764633) at select sites in select countries (selected based on study start-up timelines) were invited to participate in this cognitive function study, 20130385. There was no separate randomization for Study 20130385; data were analyzed according to Study 20110118 randomized treatment arm.

Official Title
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A Double-Blind, Placebo Controlled, Multicenter Study to Assess the Effect of Evolocumab on Cognitive Function in Patients With Clinically Evident Cardiovascular Disease and Receiving Statin Background Lipid Lowering Therapy: A Study for Subjects Enrolled in the FOURIER (Study 20110118) Trial

Conditions
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Dyslipidemia

Intervention / Treatment
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* Biological: Evolocumab
* Drug: Placebo
* Drug: Background Statin Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Randomized into Study 20110118 (FOURIER; NCT01764633) Exclusion Criteria: Current or known past diagnosis of dementia or mild cognitive impairment (MCI)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo subcutaneous injections either once every 2 weeks (Q2W) or once a month (QM) according to their own preference. Participants continued with their background statin therapy during the course of the study. | Drug: Placebo<br>* Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.<br>Drug: Background Statin Therapy<br>* Participants were required to be on a stable, high- to moderate-intensity statin background therapy consisting of an effective statin dose, ie, at least atorvastatin 20 mg daily or equivalent, and where locally approved, highly effective statin therapy (defined as at least atorvastatin 40 mg daily or equivalent) was recommended.<br>|
| Experimental: Evolocumab<br>Participants received evolocumab 140 mg Q2W or 420 mg QM subcutaneous injections according to their own preference. Participants continued with their background statin therapy during the course of the study. | Biological: Evolocumab<br>* Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.<br>* Other names: Repatha;Drug: Background Statin Therapy<br>* Participants were required to be on a stable, high- to moderate-intensity statin background therapy consisting of an effective statin dose, ie, at least atorvastatin 20 mg daily or equivalent, and where locally approved, highly effective statin therapy (defined as at least atorvastatin 40 mg daily or equivalent) was recommended.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Spatial Working Memory Strategy Index of Executive Function (6-8 Boxes) Z Score | Assessments were performed with the Cambridge Neuropsychological Test Automated Battery (CANTAB), a language-independent battery of computerized tests that is used to assess cognitive function. The Spatial Working Memory (SWM) test assesses the cognitive domain of executive function (high-level thinking and decision making). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found. The SWM strategy index of executive function represented the number of times a subject began a search with a different box. The Z score represents the standardized measure of how far an individual subject deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported. | Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Spatial Working Memory (SWM) Between-errors Z Score | Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Spatial Working Memory (SWM) between-errors test assesses the cognitive domain of working memory (holding material in mind while that material is being actively processed). Patients search for colored tokens hidden inside boxes on the screen by touching them. The critical instruction is that once a token has been found inside a box, there will never be a token hidden inside that box again, so patients must not return to a box where a token has been found. The SWM between-errors score is the number of times that a patient revisited a box in which a token had previously been found. The Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported. | Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months). | 
| Mean Change From Baseline in Paired Associated Learning (PAL) Total Errors Adjusted Z Score | The CANTAB PAL test assesses visuospatial episodic memory (storing/retrieving information by associating an event with a time and place). Boxes on the screen opened up one at a time to reveal a number of patterns. Participants were asked to remember the location of each pattern. After all the boxes had been opened, each pattern was then shown in the center of the screen in a randomized order, and the patient should touch the box where they think each pattern was hidden. The PAL total errors adjusted comprised the number of errors committed by a patient plus an adjustment for the estimated number of errors the patient would have made on any stages that were not reached. Z score represents the standardized measure of how far an individual patient deviates from the study cohort average at baseline. A higher Z score indicated better performance. The mean change from baseline averaged across all the visits is reported. | Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months). | 
| Mean Change From Baseline in Reaction Time (RTI) Median 5-choice Reaction Time Z Score | Assessments were performed with the CANTAB, a language-independent battery of computerized tests that is used to assess cognitive function. The Reaction Time (RTI) test assessed the cognitive domain of psychomotor speed (detecting and responding to a stimulus). Participants held down a button until a spot appeared in 1 of 5 circles on the screen. As soon as possible after the spot flashed up, the patient lifted their finger from the button and touched the circle in which the spot appeared. The RTI median 5-choice reaction time was the median duration between the onset of the stimulus and the release of the button. Z score represents the standardized measure of how far an individual participant deviates from the study cohort average at baseline. A higher Z score reflects better performance. The mean change from baseline averaged across all the visits is reported. | Assessments were conducted at Baseline and at weeks 24, 48, 96, 144 and end of study visit (median time on study was 19.4 months). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia