Trial Outcomes & Findings for A Phase 2a Study to Evaluate the Effect of Rilapladib (SB-659032) in Alzheimer's Disease (NCT NCT01428453)

NCT ID: NCT01428453

Last Updated: 2018-09-24

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 124 participants
• Primary outcome timeframe: Baseline (Day 0) and Week 24
• Results posted on: 2018-09-24

Participant Flow

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).

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.

Participant milestones

Measure	Placebo Once Daily 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.	Rilapladib 250 mg Once Daily 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.
Overall Study STARTED	62	61
Overall Study COMPLETED	56	52
Overall Study NOT COMPLETED	6	9

Reasons for withdrawal

Measure	Placebo Once Daily 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.	Rilapladib 250 mg Once Daily 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.
Overall Study Adverse Event	2	7
Overall Study Protocol Violation	1	0
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	3	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo Once Daily n=61 Participants 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.	Rilapladib 250 mg Once Daily n=60 Participants 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 n=121 Participants Total of all reporting groups
Age, Continuous	73.1 Years STANDARD_DEVIATION 5.40 • n=5 Participants	72.9 Years STANDARD_DEVIATION 5.15 • n=7 Participants	73.0 Years STANDARD_DEVIATION 5.26 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	32 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	28 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	61 Participants n=5 Participants	60 Participants n=7 Participants	121 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 0) and Week 24

Population: ITT population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Placebo Once Daily n=53 Participants 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.	Rilapladib 250 mg Once Daily n=48 Participants 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.
Change From Baseline (Day 0) in Cerebral Spinal Fluid (CSF) Amyloid Beta Peptide (Abeta) 42 and Abeta40 at Week 24 Abeta42	-6.3 Nanograms per Liter Standard Error 18.10	33.6 Nanograms per Liter Standard Error 19.02
Change From Baseline (Day 0) in Cerebral Spinal Fluid (CSF) Amyloid Beta Peptide (Abeta) 42 and Abeta40 at Week 24 Abeta40	-77.4 Nanograms per Liter Standard Error 181.33	-327.7 Nanograms per Liter Standard Error 190.56

PRIMARY outcome

Timeframe: Baseline (Day 0) and Week 24

Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Measure	Placebo Once Daily n=53 Participants 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.	Rilapladib 250 mg Once Daily n=48 Participants 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.
Change From Baseline (Day 0) in CSF Abeta42/ Abeta40 Ratio at Week 24	0.002 Ratio Standard Error 0.0068	0.018 Ratio Standard Error 0.0071

PRIMARY outcome

Timeframe: Baseline (Day 0) and Week 24

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Placebo Once Daily n=52 Participants 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.	Rilapladib 250 mg Once Daily n=47 Participants 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.
Change From Baseline (Day 0) in CSF Tau and Phosphorylated Tau (P-tau) Measures at Week 24 CSF tau	38.2 Nanograms per Liter Standard Error 29.98	-18.8 Nanograms per Liter Standard Error 31.90
Change From Baseline (Day 0) in CSF Tau and Phosphorylated Tau (P-tau) Measures at Week 24 P-tau	1.3 Nanograms per Liter Standard Error 1.67	-1.7 Nanograms per Liter Standard Error 1.76

PRIMARY outcome

Timeframe: Baseline (Day 0) and Week 24

Population: 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.

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.

Outcome measures

Measure	Placebo Once Daily n=56 Participants 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.	Rilapladib 250 mg Once Daily n=48 Participants 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.
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	-0.150 Scores on a scale Standard Error 0.0501	0.016 Scores on a scale Standard Error 0.0538

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 24

Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Measure	Placebo Once Daily n=46 Participants 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.	Rilapladib 250 mg Once Daily n=40 Participants 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.
Change From Baseline (Day 0) in CSF Albumin Quotients at Week 24	0.11 Nanograms per Liter Standard Error 0.172	-0.13 Nanograms per Liter Standard Error 0.184

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 24

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Placebo Once Daily n=51 Participants 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.	Rilapladib 250 mg Once Daily n=47 Participants 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.
Change From Baseline (Day 0) in Plasma Levels of Abeta42 and Abeta40 at Week 24 Abeta42	1.5 Nanograms per Liter Standard Error 0.90	0.2 Nanograms per Liter Standard Error 0.94
Change From Baseline (Day 0) in Plasma Levels of Abeta42 and Abeta40 at Week 24 Abeta40	8.8 Nanograms per Liter Standard Error 3.91	9.7 Nanograms per Liter Standard Error 4.06

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 24

Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Measure	Placebo Once Daily n=51 Participants 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.	Rilapladib 250 mg Once Daily n=47 Participants 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.
Change From Baseline (Day 0) in Plasma Levels of Abeta42/Abeta40 Ratio at Week 24	-0.010 Ratio Standard Error 0.0045	-0.012 Ratio Standard Error 0.0047

SECONDARY outcome

Timeframe: Baseline (Day 0) and Week 24

Population: ITT Population. Only those participants with data available at the indicated time points were analyzed.

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.

Outcome measures

Measure	Placebo Once Daily n=53 Participants 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.	Rilapladib 250 mg Once Daily n=47 Participants 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.
Percentage Inhibition in Plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity at Week 24	-3.86 Percent change Standard Deviation 30.228	83.59 Percent change Standard Deviation 10.483

SECONDARY outcome

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

Population: 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.

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

Outcome measures

Measure	Placebo Once Daily n=53 Participants 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.	Rilapladib 250 mg Once Daily n=53 Participants 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.
Change From Baseline (Day 0) in CogState Battery Overall Composite Score Week 12	0.013 Scores on a scale Standard Error 0.0438	-0.054 Scores on a scale Standard Error 0.0444
Change From Baseline (Day 0) in CogState Battery Overall Composite Score Week 24	-0.121 Scores on a scale Standard Error 0.0445	0.017 Scores on a scale Standard Error 0.0466

SECONDARY outcome

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

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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

Outcome measures

Measure	Placebo Once Daily n=55 Participants 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.	Rilapladib 250 mg Once Daily n=52 Participants 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.
Change From Baseline (Day 0) in CogState Battery Attention Composite Score Week 24	-0.089 Scores on a scale Standard Error 0.0686	-0.019 Scores on a scale Standard Error 0.0729
Change From Baseline (Day 0) in CogState Battery Attention Composite Score Week 12	-0.062 Scores on a scale Standard Error 0.0684	-0.125 Scores on a scale Standard Error 0.0693

Adverse Events

Placebo Once Daily

Serious events: 5 serious events

Other events: 23 other events

Deaths: 1 deaths

Rilapladib 250mg Once Daily

Serious events: 8 serious events

Other events: 16 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo Once Daily n=62 participants at risk 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.	Rilapladib 250mg Once Daily n=61 participants at risk 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.
Injury, poisoning and procedural complications Fall	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Injury, poisoning and procedural complications Fractured coccyx	1.6% 1/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	0.00% 0/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Injury, poisoning and procedural complications Scapula fracture	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Injury, poisoning and procedural complications Sternal fracture	1.6% 1/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	0.00% 0/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Gastrointestinal disorders Colitis microscopic	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Gastrointestinal disorders Inguinal hernia	1.6% 1/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	0.00% 0/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Gastrointestinal disorders Large intestine perforation	1.6% 1/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	0.00% 0/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Nervous system disorders Cerebral haemorrhage	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Nervous system disorders Complex partial seizures	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Nervous system disorders Dizziness	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Infections and infestations Upper respiratory tract infection	1.6% 1/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	0.00% 0/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Infections and infestations Vestibular neuronitis	1.6% 1/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	0.00% 0/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Cardiac disorders Bradycardia	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.

Other adverse events

Measure	Placebo Once Daily n=62 participants at risk 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.	Rilapladib 250mg Once Daily n=61 participants at risk 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.
Nervous system disorders Headache	16.1% 10/62 • Number of events 10 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	4.9% 3/61 • Number of events 3 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Gastrointestinal disorders Nausea	8.1% 5/62 • Number of events 9 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	3.3% 2/61 • Number of events 2 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Infections and infestations Urinary tract infection	9.7% 6/62 • Number of events 7 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	1.6% 1/61 • Number of events 1 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Gastrointestinal disorders Diarrhoea	3.2% 2/62 • Number of events 2 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	6.6% 4/61 • Number of events 4 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Nervous system disorders Dizziness	6.5% 4/62 • Number of events 6 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	3.3% 2/61 • Number of events 2 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.
Infections and infestations Cystitis	0.00% 0/62 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.	6.6% 4/61 • Number of events 4 • Serious Adverse Event (SAE) and non-SAE were reported for treatment period only (up to Week 24). 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.

Additional Information

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Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
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Restriction type: OTHER