The primary objective of the study is to evaluate neurocognitive function with use of Praluent after 96 weeks of treatment versus placebo.
ID
Source
Brief title
Condition
- Cardiac and vascular disorders congenital
- Vascular disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is the change in Cambridge Neuropsychological Test
Automated Battery (CANTAB) cognitive domain Spatial Working Memory (SWM)
strategy score from baseline to week 96.
Secondary outcome
Exploratory neurocognitive outcome measures to further assess neurocognitive
function in the CANTAB domains are provided below for each patient:
* Paired Associates Learning (PAL) at week 96 defined as both a PAL z-score
change from baseline and PAL raw score change from baseline, following the
definitions and rules provided for the primary neurocognitive endpoint
* Reaction Time (RTI) at week 96 defined as both a RTI z-score change from
baseline and RTI raw score change from baseline, following the definitions and
rules provided for the primary neurocognitive endpoint
* SWM between-errors score at week 96 defined as both a SWM between-errors z
score change from baseline and SWM between-errors raw score change from
baseline, following the definitions and rules provided for the primary
neurocognitive endpoint
* Global Composite score at week 96 change from baseline is defined as (the
average of the following 4 measures at week 96: SWM strategy z-score, PAL z
score, RTI z-score, and the SWM between-errors z-score) minus the average of
the same 4 z-score measures at baseline
Secondary efficacy endpoints are:
* The percent change in calculated LDL-C, apolipoprotein (Apo) B, non high
density lipoprotein (HDL) cholesterol (HDL-C), and total cholesterol (Total-C)
from baseline to weeks 12, 24, 48, 72, and 96
* The percent change in lipoprotein a [Lp(a)], HDL-C, triglyceride (TG), and
Apo A-1 from baseline to weeks 12, 24, 48, 72, and 96
* The proportion of patients reaching LDL-C <70 mg/dL (1.81 mmol/L) at weeks
12, 24, 48, 72 and 96.
* The proportion of patients reaching LDL-C <50 mg/dL (1.29 mmol/L) at weeks
12, 24, 48, 72, and 96
Background summary
Praluent was approved by the US Food and Drug Administration (FDA) in July 2015
and by the European Medicines Agency in September 2015 as a treatment for high
cholesterol for adults whose cholesterol is not controlled by diet and statin
treatment.
Observational studies have shown a relation between patients with higher
cardiovascular risk and their neurocognitive function. However, prospective
clinical trials showed variable results. The purpose of this study is to study
neurocognitive function of patients with the use of Praluent compared with
placebo.
Study objective
The primary objective of the study is to evaluate neurocognitive function with
use of Praluent after 96 weeks of treatment versus placebo.
Study design
Patients will be randomized in a 1:1 ratio to receive either placebo or 75 mg
Praluent every 2 weeks (Q2W). Randomization will be stratified by age (<65 or
*65) and by statin use (no statin, low lipophilicity of the concomitant statin,
or high lipophilicity of the concomitant statin). The study is double-blind.
Intervention
Study Drug:
Praluent
75 mg /subcutaneous (SC)/Q2W for 94 weeks
OR
Placebo matching Praluent
SC/Q2W for 94 weeks
Study burden and risks
The study-related visits may replace regular visits to the doctor and some are
additional. For the study more blood and more urine will be taken.
Also a neurocognitive test will be done. The study medication will be
administered subcutaneously (can be medication or placebo).
Known and unknown side effects can occur.
Old Saw Mill River Road 777
Tarrytown NY 10591
US
Old Saw Mill River Road 777
Tarrytown NY 10591
US
Listed location countries
Age
Inclusion criteria
1. Men and women * age 40 and * age 85
2. Patients with heFH or non-FH patients at high or very high cardiovascular risk
3. Patients with history of CHD not having adequate control of their hypercholesterolemia with LDL-C *70 mg/dL, or all other patients with LDL-C *100 mg/dL and be on a maximally-tolerated dose of statin (unless they are statin-intolerant) for at least 28 days prior to the screening visit.
4. Patients must have successfully completed the Motor Screening Task
Exclusion criteria
1. Patients with known Alzheimer*s disease or other dementia, schizophrenia, bipolar disorder, severe depression (*11 score of the Geriatric Depression Scale short form [GDS-S; Appendix 8]), cognitive impairment (<26 score of the Montreal Cognitive Assessment [MoCA]; Appendix 9]), or patients with a sleep disorder requiring daily pharmacological treatment
2. Patients >85 year old
3. Patient with a hemorrhagic stroke within last 5 years
4. History of a myocardial infarction, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, or carotid revascularization within 3 months prior to the screening visit, or endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the
screening visit.
5. eGFR <30 mL/min/1.73 m2 according to 4-variable Modification of Diet in Renal Disease Study equation (calculated by a central lab).
6. Signs and symptoms of hypothyroidism
7. History of a myocardial infarction, unstable angina leading to hospitalization, coronary artery bypass graft surgery, percutaneous coronary intervention, uncontrolled cardiac arrhythmia, carotid surgery or stenting, stroke, transient ischemic attack, or carotid revascularization within 3 months prior to the screening visit, or endovascular procedure or surgical intervention for peripheral vascular disease within 3 months prior to the screening visit
8. Pregnant or breastfeeding women
9. A positive human immunodeficiency virus (HIV) test
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003189-16-NL |
| CCMO | NL59429.028.16 |