A Phase 2a Study to Evaluate the Effect of Rilapladib (SB-659032) in Alzheimer's Disease

NCT01428453 | Completed Phase 2 Results

• 1 other identifier: 114458
• Study Type: interventional
• Target: 124
• Locations: 7 countries
• Sites: 30

Brief Summary

The study is designed to investigate the effects of rilapladib on biomarkers related to the Alzheimer's disease, and cognitive function.

Conditions

Alzheimer's Disease

Keywords

Alzheimer's disease

Outcome Measures

Primary Outcomes (4)

• Change From Baseline (Day 0) in Cerebral Spinal Fluid (CSF) Amyloid Beta Peptide (Abeta) 42 and Abeta40 at Week 24

  CSF Abeta biomarkers (Abeta42, Abeta40) were assessed at Baseline visit (Day 0) and Week 24 (Day 168). Change from Baseline in CSF Abeta42 and Abeta40 are summarized. Baseline and Week 24 study visits were taken place at approximately the same time of day in the morning (preferably between 08:00 and 12:00) to improve the reliability of CSF. Baseline value was defined as the latest Day 0 value. Change from Baseline was calculated as post-dose (Week 24) visit value minus Baseline value. The data is presented in for adjusted mean and standard error of adjusted mean.

  Baseline (Day 0) and Week 24

• Change From Baseline (Day 0) in CSF Abeta42/ Abeta40 Ratio at Week 24

  CSF Abeta biomarkers (Abeta42, Abeta40) were assessed at Baseline visit (Day 0) and Week 24 (Day 168). Change from Baseline in CSF Abeta42/Abeta40 ratio is summarized. Baseline and Week 24 study visits were taken place at approximately the same time of day in the morning (preferably between 08:00 and 12:00) to improve the reliability of CSF. Baseline value was defined as the latest Day 0 value. Change from Baseline was calculated as post-dose (Week 24) visit value minus Baseline value. The data is presented in for adjusted mean and standard error of adjusted mean.

  Baseline (Day 0) and Week 24

• Change From Baseline (Day 0) in CSF Tau and Phosphorylated Tau (P-tau) Measures at Week 24

  CSF tau and P-tau were assessed at Baseline visit (Day 0) and Week 24 (Day 168). Change from Baseline in CSF tau and P-tau was summarized. Baseline and Week 24 study visits were taken place at approximately the same time of day in the morning (preferably between 08:00 and 12:00) to improve the reliability of CSF. Baseline value was defined as the latest Day 0 value. Change from Baseline was calculated as post-dose (Week 24) visit value minus Baseline value. The data is presented in for adjusted mean and standard error of adjusted mean.

  Baseline (Day 0) and Week 24

• Change From Baseline (Day 0) in the Computerized Test Battery for Cognition (CogState) Battery Working Memory/Executive Function (WM/EF) Composite Score at Week 24

  The WM/EF composite score was comprised of 5 functional tests including 1) Controlled oral word association which measured language fluency, planning and working memory, 2) Category naming: It measures semantic fluency, planning and working memory, 3) One-back: This is a measure of working memory. 4) Trail B: This is a measure of motor speed, visual scanning, and visual-motor integration. This test required attention and cognitive flexibility. 5) Go No-Go task: This test evaluate accuracy and reaction time for each response. The composite score calculated by standardizing the total score: sum of all responses obtained from these 5 functional test by using the formula (Total score of ITT population at baseline - Total score at Week 24) /standard deviation of mean total mean score at baseline. The observed composite score ranged from minimum -1.474 and maximum 1.596. Lower score means better cognitive status. Change from Baseline was calculated as post-dose visit minus Baseline value.

  Baseline (Day 0) and Week 24

Secondary Outcomes (6)

• Change From Baseline (Day 0) in CSF Albumin Quotients at Week 24

  Baseline (Day 0) and Week 24

• Change From Baseline (Day 0) in Plasma Levels of Abeta42 and Abeta40 at Week 24

  Baseline (Day 0) and Week 24

• Change From Baseline (Day 0) in Plasma Levels of Abeta42/Abeta40 Ratio at Week 24

  Baseline (Day 0) and Week 24

• Percentage Inhibition in Plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity at Week 24

  Baseline (Day 0) and Week 24

• Change From Baseline (Day 0) in CogState Battery Overall Composite Score

  Baseline (Day 0) and Week 12 (Day 84), Week 24 (Day 168)

Study Arms (2)

250mg rilapladib

EXPERIMENTAL

Experimental drug

Drug: 250mg rilapladib

placebo

PLACEBO COMPARATOR

Placebo comparator

Drug: placebo

Interventions

250mg rilapladib DRUG

Experimental Drug

250mg rilapladib

placebo DRUG

Placebo comparator

placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A clinical diagnosis of possible Alzheimer's disease in accordance with the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, with radiological (Magnetic Resonance Imaging \[MRI\] or Computed Tomography \[CT\]) evidence of significant cerebrovascular disease (CVD), assessed within the last 12 months
• Male or female between 50 and 80 years of age inclusive, at the time of signing the informed consent.
• Subject has a documented history of at least 6 months of ongoing Alzheimer's disease therapy (AChEIs and/or memantine) with stable dosing for at least the last 2 months (and with no intent to change for the duration of the study).
• Mini-Mental Status Examination (MMSE) score between 20 and 26 at Screening.
• Clinical Dementia Rating Scale (CDR) score of 0.5 or 1.0 at Screening.
• A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea; or of child-bearing potential and agrees to use acceptable contraception methods
• Subject has provided full written informed consent prior to the performance of any protocol-specified procedure; or if the subject is unable to provide informed consent due to cognitive status, the subject will provide assent and full written informed consent will be provided by a legally acceptable representative
• The subject has a dedicated caregiver who is willing to supervise participation in the study
• In the opinion of the investigator, the subject has the ability to comply with study procedures (cognitive and other testing) and is fluent in the language used for the administration of the cognitive tests.

You may not qualify if:

• History and/or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. structural or developmental abnormality, epilepsy, infectious, degenerative or inflammatory/demyelinating CNS conditions such as, Parkinson's disease and frontotemporal dementia
• History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study; major depressive disorder (according to DSM-IV) in the past year; current active depression requiring initiation of treatment (or is believed to account for substantial degree of cognitive impairment)
• Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology (unless neurosyphilis was ruled out) or active thyroid dysfunction (particularly suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH), where this is thought to be the cause of, or to contribute to the severity of the subject's dementia.
• History of alcohol or other substance abuse, according to the DSM-IV criteria, or recent or remote history of the same if that could be a contributing factor to dementia.
• History of intra cerebral haemorrhage due to any of the following causes: cerebral amyloid angiopathy, uncontrolled hypertension, cerebral arteriovenous malformation, coagulopathy, CNS vasculitis or any other condition that the investigator and/or medical monitor considers as a relevant risk factor for intracerebral haemorrhage
• Recent (i.e.,\<6 months from Screening Visit) cardiovascular event defined as:
• ST-elevation MI or non-ST-elevation MI, confirmed by cardiac enzyme elevation and ECG changes
• coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft )
• stroke of any etiology
• resuscitated sudden death
• prior carotid surgery or stenting procedure
• Poorly controlled hypertension despite lifestyle modifications and pharmacotherapy (either systolic blood pressure \>160mmHg or diastolic blood pressure \>110mmHg)
• QTcB interval \>450 msec; or QTcB \> 480 msec in subjects with bundle branch block based on ECG assessment at the Screening visit.
• HbA1c \>12.0 at Screening, or uncontrolled diabetes in the opinion of the investigator.
• History of glaucoma or any other findings in the baseline eye exam that, in the opinion of the investigator, would exclude the subject from participation in the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (30)

GSK Investigational Site

Sofia, 1113, Bulgaria

Location

GSK Investigational Site

Sofia, 1431, Bulgaria

Location

GSK Investigational Site

Toronto, Ontario, M3B 2S7, Canada

Location

GSK Investigational Site

Gatineau, Quebec, J9A 1K7, Canada

Location

GSK Investigational Site

Sherbrooke, Quebec, J1H 1Z1, Canada

Location

GSK Investigational Site

Ellwangen, Baden-Wurttemberg, 73479, Germany

Location

GSK Investigational Site

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

GSK Investigational Site

Ulm, Baden-Wurttemberg, 89081, Germany

Location

GSK Investigational Site

Alzenau in Unterfranken, Bavaria, 63755, Germany

Location

GSK Investigational Site

Bad Homburg, Hesse, 61348, Germany

Location

GSK Investigational Site

Achim, Lower Saxony, 28832, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30559, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44787, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44791, Germany

Location

GSK Investigational Site

Bochum, North Rhine-Westphalia, 44892, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50935, Germany

Location

GSK Investigational Site

Oldenburg in Holstein, Schleswig-Holstein, 26122, Germany

Location

GSK Investigational Site

Rome, Lazio, 00185, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Brescia, Lombardy, 25125, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20122, Italy

Location

GSK Investigational Site

Verona, Veneto, 37134, Italy

Location

GSK Investigational Site

Lørenskog, 1478, Norway

Location

GSK Investigational Site

Baracaldo/Vizcaya, 48903, Spain

Location

GSK Investigational Site

Barcelona, 08014, Spain

Location

GSK Investigational Site

Castellon, 12004, Spain

Location

GSK Investigational Site

Getafe/Madrid, 28905, Spain

Location

GSK Investigational Site

L'Hospitalet de Llobregat, 08907, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Stockholm, se-141 86, Sweden

Location

Related Publications (1)

• Maher-Edwards G, De'Ath J, Barnett C, Lavrov A, Lockhart A. A 24-week study to evaluate the effect of rilapladib on cognition and cerebrospinal fluid biomarkers of Alzheimer's disease. Alzheimers Dement (N Y). 2015 Jun 30;1(2):131-140. doi: 10.1016/j.trci.2015.06.003. eCollection 2015 Sep.

  PMID: 29854933 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Alzheimer Disease

Interventions

rilapladib

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2011
• First Posted: September 5, 2011
• Study Start: October 1, 2011
• Primary Completion: February 4, 2013
• Study Completion: February 18, 2013
• Last Updated: September 24, 2018
• Results First Posted: September 24, 2018

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will share

Locations

IT (5); NO (1); SE (1); CA (3); BU (2); ES (6); DE (12)