ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT01428453
Recruitment Status : Completed
First Posted : September 5, 2011
Results First Posted : September 24, 2018
Last Update Posted : September 24, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: 250mg rilapladib
Drug: placebo
Enrollment 124
Recruitment Details Participants with Alzheimer’s disease (AD) were randomized to either rilapladib or placebo from October-2011 to February-2013. The study duration was approximately 30 weeks (screening: 4 weeks, treatment: 24 weeks and follow-up: 2 weeks).
Pre-assignment Details Total of 170 participants were screened, of which 124 were randomized in 24 centres. Out of 124 participants, one was excluded from safety population due to randomization error. Out of 123 participants, 2 were excluded due to unavailability of post-baseline efficacy data. Intention to treat (ITT) population consisted of 121 participants.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition, to their stable background therapy consisting of an acetylcholinesterase inhibitor (AChEI) and/or memantine. Participants randomized to receive oral rilapladib 250 milligrams (mg) tablet once daily following breakfast for a period of 24 weeks. In addition, to their stable background therapy consisting of an AChEI and/or memantine.
Period Title: Overall Study
Started 62 61
Completed 56 52
Not Completed 6 9
Reason Not Completed
Adverse Event             2             7
Protocol Violation             1             0
Lost to Follow-up             0             1
Withdrawal by Subject             3             1
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily Total
Hide Arm/Group Description Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine. Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine. Total of all reporting groups
Overall Number of Baseline Participants 61 60 121
Hide Baseline Analysis Population Description
The data for ITT population is presented and defined as participants who were randomized, received at least one dose of study medication and had at least one non-missing post Baseline efficacy assessment. One participant from each group was excluded from ITT population as no post-baseline efficacy data available and total ITT population was 121.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 61 participants 60 participants 121 participants
73.1  (5.40) 72.9  (5.15) 73.0  (5.26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 60 participants 121 participants
Female
28
  45.9%
32
  53.3%
60
  49.6%
Male
33
  54.1%
28
  46.7%
61
  50.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White - White/Caucasian/European Heritage Number Analyzed 61 participants 60 participants 121 participants
61
 100.0%
60
 100.0%
121
 100.0%
1.Primary Outcome
Title Change From Baseline (Day 0) in Cerebral Spinal Fluid (CSF) Amyloid Beta Peptide (Abeta) 42 and Abeta40 at Week 24
Hide Description 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.
Time Frame Baseline (Day 0) and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 53 48
Least Squares Mean (Standard Error)
Unit of Measure: Nanograms per Liter
Abeta42 -6.3  (18.10) 33.6  (19.02)
Abeta40 -77.4  (181.33) -327.7  (190.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.133
Comments [Not Specified]
Method ANCOVA
Comments The analysis method was ANCOVA adjusted for Treatment, Baseline CSF Abeta1-42 and Age.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 39.8
Confidence Interval (2-Sided) 95%
-12.4 to 92.0
Estimation Comments Comparison of CSF Abeta42 between placebo and rilapladib 250 mg.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.829
Comments [Not Specified]
Method ANCOVA
Comments The analysis method was ANCOVA adjusted for Treatment, Baseline CSF Abeta1-40 and Age.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -250.3
Confidence Interval (2-Sided) 95%
-771.9 to 271.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 265.66
Estimation Comments Comparison of CSF Abeta40 between placebo and rilapladib 250 mg.
2.Primary Outcome
Title Change From Baseline (Day 0) in CSF Abeta42/ Abeta40 Ratio at Week 24
Hide Description 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.
Time Frame Baseline (Day 0) and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 53 48
Least Squares Mean (Standard Error)
Unit of Measure: Ratio
0.002  (0.0068) 0.018  (0.0071)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.016
Confidence Interval (2-Sided) 95%
-0.003 to 0.036
Estimation Comments The analysis method was ANCOVA adjusted for Treatment, Baseline CSF Ratio Abeta1-42/Abeta1-40 and Age.
3.Primary Outcome
Title Change From Baseline (Day 0) in CSF Tau and Phosphorylated Tau (P-tau) Measures at Week 24
Hide Description 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.
Time Frame Baseline (Day 0) and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 52 47
Least Squares Mean (Standard Error)
Unit of Measure: Nanograms per Liter
CSF tau Number Analyzed 52 participants 46 participants
38.2  (29.98) -18.8  (31.90)
P-tau Number Analyzed 52 participants 47 participants
1.3  (1.67) -1.7  (1.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.902
Comments [Not Specified]
Method ANCOVA
Comments The analysis method was ANCOVA adjusted for Treatment, Baseline CSF tau and Age.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -57.1
Confidence Interval (2-Sided) 95%
-144.5 to 30.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 44.40
Estimation Comments Comparison of CSF tau between placebo and rilapladib 250 mg.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.892
Comments [Not Specified]
Method ANCOVA
Comments The analysis method was ANCOVA adjusted for Treatment, Baseline CSF P-tau and Age.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-7.9 to 1.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.46
Estimation Comments Comparison of P-tau between placebo and rilapladib 250 mg.
4.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (Day 0) and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed. The data is presented in for adjusted mean and standard error of adjusted mean.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 56 48
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-0.150  (0.0501) 0.016  (0.0538)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline Working Memory/Executive Function Composite Score, Treatment by Visit and Baseline Working Memory/Executive Function Composite Score by Visit.
Method Mixed-Model Repeated Measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.167
Confidence Interval (2-Sided) 95%
0.021 to 0.313
Estimation Comments A positive treatment difference indicates benefit, relative to placebo.
5.Secondary Outcome
Title Change From Baseline (Day 0) in CSF Albumin Quotients at Week 24
Hide Description CSF albumin quotient was assessed at Baseline visit (Day 0) and Week 24 (Day 168). Change from Baseline in albumin quotient 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.
Time Frame Baseline (Day 0) and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 46 40
Least Squares Mean (Standard Error)
Unit of Measure: Nanograms per Liter
0.11  (0.172) -0.13  (0.184)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.828
Comments [Not Specified]
Method ANCOVA
Comments The analysis method was ANCOVA adjusted for Treatment, Baseline CSF Albumin Quotient and Age.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.74 to 0.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.256
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline (Day 0) in Plasma Levels of Abeta42 and Abeta40 at Week 24
Hide Description Plasma Abeta biomarkers (Abeta42, Abeta40) were assessed at Baseline visit (Day 0) and Week 24 (Day 168). Change from Baseline in plasma Abeta42 and Abeta40 are summarized. 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.
Time Frame Baseline (Day 0) and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 51 47
Least Squares Mean (Standard Error)
Unit of Measure: Nanograms per Liter
Abeta42 1.5  (0.90) 0.2  (0.94)
Abeta40 8.8  (3.91) 9.7  (4.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed-Model Repeated Measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-3.9 to 1.2
Estimation Comments Comparison of Abeta42 between placebo and rilapladib 250 mg. The analysis method for Plasma parameters was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline, Treatment by Visit, Baseline by Visit and Age.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed-Model Repeated Measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.0
Confidence Interval 95%
-10.2 to 12.2
Estimation Comments Comparison of Abeta40 between placebo and rilapladib 250 mg. The analysis method for Plasma parameters was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline, Treatment by Visit, Baseline by Visit and Age.
7.Secondary Outcome
Title Change From Baseline (Day 0) in Plasma Levels of Abeta42/Abeta40 Ratio at Week 24
Hide Description Plasma Abeta biomarkers (Abeta42, Abeta40) were assessed at Baseline visit (Day 0) and Week 24 (Day 168). Change from Baseline in plasma Abeta42/Abeta40 ratio is summarized. 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.
Time Frame Baseline (Day 0) and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 51 47
Least Squares Mean (Standard Error)
Unit of Measure: Ratio
-0.010  (0.0045) -0.012  (0.0047)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed-Model Repeated Measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.003
Confidence Interval (2-Sided) 95%
-0.016 to 0.010
Estimation Comments The analysis method for Plasma parameters was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline, Treatment by Visit, Baseline by Visit and Age.
8.Secondary Outcome
Title Percentage Inhibition in Plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity at Week 24
Hide Description Plasma Lp-PLA2 was assessed at Baseline visit (Day 0) and Week 24 (Day 168). Percentage inhibition in plasma Lp-PLA2 activity ratio is summarized. Percentage inhibition was calculated by dividing change from Baseline in plasma LpPLA2 by Baseline LpPLA2 multiplied by -100. 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.
Time Frame Baseline (Day 0) and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 53 47
Mean (Standard Deviation)
Unit of Measure: Percent change
-3.86  (30.228) 83.59  (10.483)
9.Secondary Outcome
Title Change From Baseline (Day 0) in CogState Battery Overall Composite Score
Hide Description CogState battery overall composite score comprised of 8 functional tests 1) Controlled oral word association test measured language fluency, planning and working memory. 2) Category naming test measured semantic fluency, planning and working memory. 3) One-back test measured working memory. 4) Trail B test measured motor speed, visual scanning and visual-motor integration, required attention and cognitive flexibility. 5) Go No-Go task evaluated accuracy and reaction time for each response. 6) International shopping list immediate and delayed recall tests measured episodic memory. 7) Identification task test assessed visual attention. 8) Trail A test measured psychomotor speed and attention. Composite score= total score (sum of all responses from 8 functional test) by formula (Total score at baseline - Week 24) / SD of total score at baseline. Score ranged: -1.070 to 0.907. Lower score indicated the better cognitive status. Change from Baseline= post-dose visit minus Baseline value
Time Frame Baseline (Day 0) and Week 12 (Day 84), Week 24 (Day 168)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed. The data is presented in for adjusted mean and standard error of adjusted mean.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 53 53
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 12 Number Analyzed 52 participants 53 participants
0.013  (0.0438) -0.054  (0.0444)
Week 24 Number Analyzed 53 participants 48 participants
-0.121  (0.0445) 0.017  (0.0466)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed-Model Repeated Measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.067
Confidence Interval (2-Sided) 95%
-0.191 to 0.057
Estimation Comments

The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline Score, Treatment by Visit and Baseline Score by Visit. A positive treatment difference indicates benefit, relative to placebo.

placebo.

Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.982
Comments The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline Overall Composite Score, Treatment by Visit and Baseline Overall Composite Score by Visit.
Method Mixed-Model Repeated Measures analysis
Comments The probability (effect size) for change from Baseline in CogState battery overall composite score >0 is presented.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.138
Confidence Interval (2-Sided) 95%
0.010 to 0.267
Estimation Comments A positive treatment difference indicates benefit, relative to placebo. Comparison of overall composite score between placebo and rilapladib 250 mg at Week 24.
10.Secondary Outcome
Title Change From Baseline (Day 0) in CogState Battery Attention Composite Score
Hide Description CogState battery attention composite score comprised of 2 functional tests including 1) Identification task test assessed visual attention and 2) Trail A test measured psychomotor speed and attention. Composite score calculated by standardizing the total score (sum of all responses from 2 functional test) by formula (Total score at baseline - Week 24) / SD of total score at baseline. The observed composite score ranged from minimum -1.756 and maximum 1.330. Higher score indicated the better attention. Baseline value was defined as the latest Day 0 value and Change from Baseline was calculated as post-dose visit minus Baseline value
Time Frame Baseline (Day 0) and Week 12 (Day 84), Week 24 (Day 168)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Once Daily Rilapladib 250 mg Once Daily
Hide Arm/Group Description:
Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
Overall Number of Participants Analyzed 55 52
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 12 Number Analyzed 53 participants 52 participants
-0.062  (0.0684) -0.125  (0.0693)
Week 24 Number Analyzed 55 participants 48 participants
-0.089  (0.0686) -0.019  (0.0729)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed-Model Repeated Measures analysis
Comments The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline Score, Treatment by Visit and Baseline Score by Visit.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.063
Confidence Interval (2-Sided) 95%
-0.257 to 0.130
Estimation Comments Comparison of attention composite score between placebo and rilapladib 250 mg at Week 12. A positive treatment difference indicates benefit, relative to placebo.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Once Daily, Rilapladib 250 mg Once Daily
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed-Model Repeated Measures analysis
Comments The analysis method was Mixed-Model Repeated Measures adjusted for Treatment, Visit, Baseline Score, Treatment by Visit and Baseline Score by Visit.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.070
Confidence Interval (2-Sided) 95%
-0.130 to 0.269
Estimation Comments Comparison of attention composite score between placebo and rilapladib 250 mg at Week 24. A positive treatment difference indicates benefit, relative to placebo.
Time Frame Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24).
Adverse Event Reporting Description The safety population was used and defined as consisting of all participants who were randomized and received at least one dose of double-blind medication.
 
Arm/Group Title Placebo Once Daily Rilapladib 250mg Once Daily
Hide Arm/Group Description Participants randomized to receive oral placebo tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine. Participants randomized to receive oral rilapladib 250 mg tablet once daily following breakfast for a period of 24 weeks. In addition to their stable background therapy consisting of an AChEI and/or memantine.
All-Cause Mortality
Placebo Once Daily Rilapladib 250mg Once Daily
Affected / at Risk (%) Affected / at Risk (%)
Total   1/62 (1.61%)      1/61 (1.64%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Once Daily Rilapladib 250mg Once Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/62 (8.06%)      8/61 (13.11%)    
Cardiac disorders     
Bradycardia  1  0/62 (0.00%)  1/61 (1.64%) 
Gastrointestinal disorders     
Colitis microscopic  1  0/62 (0.00%)  1/61 (1.64%) 
Inguinal hernia  1  1/62 (1.61%)  0/61 (0.00%) 
Large intestine perforation  1  1/62 (1.61%)  0/61 (0.00%) 
Infections and infestations     
Upper respiratory tract infection  1  1/62 (1.61%)  0/61 (0.00%) 
Vestibular neuronitis  1  1/62 (1.61%)  0/61 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  0/62 (0.00%)  1/61 (1.64%) 
Femoral neck fracture  1  0/62 (0.00%)  1/61 (1.64%) 
Fractured coccyx  1  1/62 (1.61%)  0/61 (0.00%) 
Scapula fracture  1  0/62 (0.00%)  1/61 (1.64%) 
Sternal fracture  1  1/62 (1.61%)  0/61 (0.00%) 
Nervous system disorders     
Cerebral haemorrhage  1  0/62 (0.00%)  1/61 (1.64%) 
Complex partial seizures  1  0/62 (0.00%)  1/61 (1.64%) 
Dizziness  1  0/62 (0.00%)  1/61 (1.64%) 
1
Term from vocabulary, MedDRA version 16.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Once Daily Rilapladib 250mg Once Daily
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/62 (37.10%)      16/61 (26.23%)    
Gastrointestinal disorders     
Nausea  1  5/62 (8.06%)  9 2/61 (3.28%)  2
Diarrhoea  1  2/62 (3.23%)  2 4/61 (6.56%)  4
Infections and infestations     
Urinary tract infection  1  6/62 (9.68%)  7 1/61 (1.64%)  1
Cystitis  1  0/62 (0.00%)  0 4/61 (6.56%)  4
Nervous system disorders     
Headache  1  10/62 (16.13%)  10 3/61 (4.92%)  3
Dizziness  1  4/62 (6.45%)  6 2/61 (3.28%)  2
1
Term from vocabulary, MedDRA version 16.0
Indicates events were collected by systematic assessment
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.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01428453     History of Changes
Other Study ID Numbers: 114458
First Submitted: September 1, 2011
First Posted: September 5, 2011
Results First Submitted: March 7, 2017
Results First Posted: September 24, 2018
Last Update Posted: September 24, 2018