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Evaluating PCSK9 Binding antiBody Influence oN coGnitive HeAlth in High cardiovascUlar Risk Subjects (EBBINGHAUS)

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ClinicalTrials.gov Identifier: NCT02207634
Recruitment Status : Completed
First Posted : August 4, 2014
Results First Posted : January 15, 2018
Last Update Posted : January 15, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Dyslipidemia Biological: Evolocumab Drug: Placebo Drug: Background Statin Therapy Phase 3

Detailed Description:
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.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1974 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: 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
Actual Study Start Date : September 10, 2014
Primary Completion Date : November 11, 2016
Study Completion Date : November 11, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Statins
Drug Information available for: Evolocumab
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Placebo Comparator: Placebo
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
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
Drug: Background Statin Therapy
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.
Experimental: Evolocumab
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
Administered subcutaneously using a spring-based prefilled 1.0 mL autoinjector/pen.
Other Names:
  • AMG 145
  • Repatha
Drug: Background Statin Therapy
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.


Outcome Measures

Primary Outcome Measures :
  1. Mean Change From Baseline in Spatial Working Memory Strategy Index of Executive Function (6-8 Boxes) Z Score [ Time Frame: 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). ]

    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.



Secondary Outcome Measures :
  1. Mean Change From Baseline in Spatial Working Memory (SWM) Between-errors Z Score [ Time Frame: 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). ]

    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.


  2. Mean Change From Baseline in Paired Associated Learning (PAL) Total Errors Adjusted Z Score [ Time Frame: 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). ]

    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.


  3. Mean Change From Baseline in Reaction Time (RTI) Median 5-choice Reaction Time Z Score [ Time Frame: 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). ]
    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.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Randomized into Study 20110118 (FOURIER; NCT01764633)

Exclusion Criteria:

  • Current or known past diagnosis of dementia or mild cognitive impairment (MCI)
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02207634


  Show 417 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02207634     History of Changes
Other Study ID Numbers: 20130385
2014-001976-75 ( EudraCT Number )
First Posted: August 4, 2014    Key Record Dates
Results First Posted: January 15, 2018
Last Update Posted: January 15, 2018
Last Verified: December 2017

Keywords provided by Amgen:
High cholesterol
Treatment for high cholesterol
Lowering cholesterol
Lowering high cholesterol
Hypercholesterolemia

Additional relevant MeSH terms:
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Lipid Regulating Agents