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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01428453
• Collaborator: (none)
• Enrollment: 124
• Locations: 30
• Arms: 2
• Duration (Months): 16.6
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: 250mg rilapladib; Drug: placebo	Phase 2

Detailed Description

The study is in subjects with Alzheimer's disease and evidence of cerebrovascular disease (CVD) who are currently treated with an acetylcholinesterase inhibitor (AChEI) and/or memantine. The study is a randomized, double-blind, placebo controlled, parallel group, repeat dose design, in which subjects (up to 60 randomized subjects per arm) will receive oral placebo or rilapladib (250 mg), once daily for 24 weeks in addition to their stable background AD therapy consisting of an acetylcholinesterase inhibitor (AChEI) and/or memantine. Subjects will take 250mg of rilapladib or placebo once daily for a period of 24 weeks. The total duration of participation for each subject will be approximately 30 weeks comprising approximately 4 weeks screening, 24 weeks treatment and 2 weeks follow-up. From the time of randomization and throughout the treatment period subjects will attend visits after 1 week, 4 weeks and thereafter every 4 weeks until Week 24. A follow-up visit will occur approximately 2 weeks after the final dose of study medication. Cognitive assessments will be performed at the screening visit, at the randomization (baseline) visit and at weeks 12 and 24 of the treatment period. Cerebrospinal fluid (CSF) samples will be taken via lumbar puncture at baseline and Week 24 for biomarker analyses related to Alzheimer's disease. Blood samples will be collected throughout the study for pharmacokinetics and a range of biomarker analyses. A range of safety and tolerability assessments will also be performed (including vital signs, laboratory tests, eye examinations and ECGs).

Study Design

• Study Type: Interventional
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Study to Evaluate the Effect of Rilapladib (SB-659032) on Biomarkers Related to the Pathogenesis and Progression of Alzheimer's Disease
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Feb 4, 2013
• Actual Study Completion Date: Feb 18, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 250mg rilapladib Experimental drug	Drug: 250mg rilapladib; Experimental Drug
Placebo Comparator: placebo Placebo comparator	Drug: placebo; Placebo comparator

Outcome Measures

Primary Outcome Measures

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

2. Change From Baseline (Day 0) in CSF Abeta42/ Abeta40 Ratio at Week 24 [Baseline (Day 0) and 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.

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

4. 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 [Baseline (Day 0) and 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.

Secondary Outcome Measures

1. Change From Baseline (Day 0) in CSF Albumin Quotients at Week 24 [Baseline (Day 0) and Week 24]

   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.

2. Change From Baseline (Day 0) in Plasma Levels of Abeta42 and Abeta40 at Week 24 [Baseline (Day 0) and Week 24]

   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.

3. Change From Baseline (Day 0) in Plasma Levels of Abeta42/Abeta40 Ratio at Week 24 [Baseline (Day 0) and Week 24]

   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.

4. Percentage Inhibition in Plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity at Week 24 [Baseline (Day 0) and Week 24]

   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.

5. Change From Baseline (Day 0) in CogState Battery Overall Composite Score [Baseline (Day 0) and Week 12 (Day 84), Week 24 (Day 168)]

   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

6. Change From Baseline (Day 0) in CogState Battery Attention Composite Score [Baseline (Day 0) and Week 12 (Day 84), Week 24 (Day 168)]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 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

2. Male or female between 50 and 80 years of age inclusive, at the time of signing the informed consent.

3. 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).

4. Mini-Mental Status Examination (MMSE) score between 20 and 26 at Screening.

5. Clinical Dementia Rating Scale (CDR) score of 0.5 or 1.0 at Screening.

6. 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

7. 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

8. The subject has a dedicated caregiver who is willing to supervise participation in the study

9. 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.

Exclusion Criteria:

1. 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

2. 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)

3. 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.

4. 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.

5. 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

6. Recent (i.e.,<6 months from Screening Visit) cardiovascular event defined as:

7. ST-elevation MI or non-ST-elevation MI, confirmed by cardiac enzyme elevation and ECG changes

8. coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft )

9. stroke of any etiology

10. resuscitated sudden death

11. prior carotid surgery or stenting procedure

12. Poorly controlled hypertension despite lifestyle modifications and pharmacotherapy (either systolic blood pressure >160mmHg or diastolic blood pressure >110mmHg)

13. QTcB interval >450 msec; or QTcB > 480 msec in subjects with bundle branch block based on ECG assessment at the Screening visit.

14. HbA1c >12.0 at Screening, or uncontrolled diabetes in the opinion of the investigator.

15. 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.

16. History of adult asthma (or reactive airway disease) manifested by bronchospasm in the past 6 months, or currently taking regular anti-asthmatic medication(s).

17. Previous history of anaphylaxis, severe allergic reaction or history of hypersensitivity to any of the components of the formulation.

18. Significant abnormalities on clinical chemistry, haematology or urinalysis at Screening, including clinically significant anaemia.

19. History of chronic viral hepatitis (including presence of B surface antigen or hepatitis C antibody), or other chronic hepatic disorders.

20. Abnormal Screening blood tests exceeding any of the limits defined below:

21. Alanine transaminase (ALT) or aspartate transaminase (AST) >1.5 x the upper limit of normal (ULN)

22. Alkaline phosphatase (AP) and bilirubin >1.5X ULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

23. Calculated creatinine clearance < 30 ml/min (per Cockcroft & Gault) at Screening

24. Other clinically significant abnormality on physical (including neurological), laboratory or ECG examination that could be detrimental to the subject in the opinion of the Investigator or could compromise the integrity of the study.

25. Planned major surgery within the study period.

26. Use of systemic steroids or other immunosuppressants within the last 30 days prior to screening.

27. Current treatment with barbiturates, MAO inhibitors, butyrophenones, phenothiazines and other "conventional" antipsychotic within 30 days or 5 half-lives prior to Screening, whichever is longer.

28. Treatment with antidepressants, (other than MAO inhibitors), thyroid hormones, atypical antipsychotics (e.g. risperidone), benzodiazepines and other sedatives / hypnotics unless prescribed at a stable dose for at least 2 months prior to Screening. Note: Benzodiazepines or other sedatives/hypnotics (including antihistamines) with half-life less than 6 hours can be taken on a prn (as needed) basis but must not be taken within 5 half lives prior to cognitive testing.

29. Current treatment with known potent inhibitors of CYP3A4 (e.g. ketoconazole, rifampin, modafinil).

30. Current treatment with known potent Pgp inhibitors (itraconazole, ketoconazole, cyclosporin, loperamide, diltiazem, verapamil, spironolactone, quinidine, bepridil, quinine, carvedilol)

31. Cognitive tasks prescribed for cognitive rehabilitation and performed under medical supervision in the 6 months prior to screening and/or during study

32. Investigational medications or devices including symptomatic AD treatment during the 60 days prior to the Screening visit, or within 5 half-lives of use of the investigational drug prior to the Screening Visit, whichever is longer.

33. Participation in another investigational drug (with the exception of anti-amyloid monoclonal antibodies [mAbs]) or device study where subject was treated chronically (i.e. > 1 single dose) with a study agent intended to impact AD progression during the 12 months prior to the Screening visit.

34. Subjects who participated in an investigational drug study that involved chronic dosing with a monoclonal antibody at any time in the past are excluded from this study, unless it is known that they received placebo during the previous study.

35. Subjects who participated in previous single-dose studies of anti-amyloid mAbs will be permitted provided the subject's dose of the mAb is at least 5 half-lives removed; the subjects did not experience any moderate adverse events classified as possibly drug-related or any serious adverse event during that study; the subject did not drop out of the previous study (i.e. completed all safety assessments)

36. Subjects, who in the investigator's judgement, pose a significant suicide risk (e.g. history of suicidal behaviour in the last 6 months and/or any suicidal ideation of type 4 or 5 on the C-SSRS in the last 2 months).

37. Subject or caregiver is an immediate family member or employee of the participating Investigator, any of the participating site staff or GSK staff.

38. Any contraindication to lumbar puncture or insertion of CSF catheter, including but not limited to

39. Thrombocytopenia or other coagulation disorders (including subjects receiving coumarin-derived anti-coagulants or low-molecular-weight heparin).

40. The presence of cutaneous or soft tissue infection overlying or adjacent to the site of lumbar puncture.

41. Previous spinal surgery that could complicate access to the subarachnoid space.

42. Suspicion of increased intracranial pressure due to a cerebral mass.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Sofia		Bulgaria	1113
2	GSK Investigational Site	Sofia		Bulgaria	1431
3	GSK Investigational Site	Toronto	Ontario	Canada	M3B 2S7
4	GSK Investigational Site	Gatineau	Quebec	Canada	J9A 1K7
5	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 1Z1
6	GSK Investigational Site	Ellwangen	Baden-Wuerttemberg	Germany	73479
7	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg	Germany	72076
8	GSK Investigational Site	Ulm	Baden-Wuerttemberg	Germany	89081
9	GSK Investigational Site	Alzenau	Bayern	Germany	63755
10	GSK Investigational Site	Bad Homburg	Hessen	Germany	61348
11	GSK Investigational Site	Achim	Niedersachsen	Germany	28832
12	GSK Investigational Site	Hannover	Niedersachsen	Germany	30559
13	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44787
14	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44791
15	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44892
16	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50935
17	GSK Investigational Site	Oldenburg	Schleswig-Holstein	Germany	26122
18	GSK Investigational Site	Roma	Lazio	Italy	00185
19	GSK Investigational Site	Genova	Liguria	Italy	16132
20	GSK Investigational Site	Brescia	Lombardia	Italy	25125
21	GSK Investigational Site	Milano	Lombardia	Italy	20122
22	GSK Investigational Site	Verona	Veneto	Italy	37134
23	GSK Investigational Site	Lørenskog		Norway	1478
24	GSK Investigational Site	Baracaldo/Vizcaya		Spain	48903
25	GSK Investigational Site	Barcelona		Spain	08014
26	GSK Investigational Site	Castellón de La Plana		Spain	12004
27	GSK Investigational Site	Getafe/Madrid		Spain	28905
28	GSK Investigational Site	L'Hospitalet de Llobregat		Spain	08907
29	GSK Investigational Site	Madrid		Spain	28006
30	GSK Investigational Site	Stockholm		Sweden	se-141 86

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01428453
• Other Study ID Numbers: 114458
• First Posted: Sep 5, 2011
• Last Update Posted: Sep 24, 2018
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Alzheimer's disease
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	Placebo Once Daily	Rilapladib 250 mg Once Daily	Total
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 Participants	61	60	121
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	73.1 (5.40)	72.9 (5.15)	73.0 (5.26)
Sex: Female, Male (Count of Participants)
Female	28 45.9%	32 53.3%	60 49.6%
Male	33 54.1%	28 46.7%	61 50.4%
Race/Ethnicity, Customized (Count of Participants)
White - White/Caucasian/European Heritage	61 100%	60 100%	121 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	53	48
Abeta42	-6.3 (18.10)	33.6 (19.02)
Abeta40	-77.4 (181.33)	-327.7 (190.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.133
	Comments
	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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Comparison of CSF Abeta42 between placebo and rilapladib 250 mg.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.829
	Comments
	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
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

Outcome Measure Data

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
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.
Measure Participants	53	48
Least Squares Mean (Standard Error) [Ratio]	0.002 (0.0068)	0.018 (0.0071)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.016
	Confidence Interval	(2-Sided) 95%; -0.003 to 0.036
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
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.
Measure Participants	52	47
CSF tau	38.2 (29.98)	-18.8 (31.90)
P-tau	1.3 (1.67)	-1.7 (1.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.902
	Comments
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.892
	Comments
	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
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

Outcome Measure Data

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
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.
Measure Participants	56	48
Least Squares Mean (Standard Error) [Scores on a scale]	-0.150 (0.0501)	0.016 (0.0538)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.167
	Confidence Interval	(2-Sided) 95%; 0.021 to 0.313
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
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.
Measure Participants	46	40
Least Squares Mean (Standard Error) [Nanograms per Liter]	0.11 (0.172)	-0.13 (0.184)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.828
	Comments
	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

6. Secondary Outcome

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

Outcome Measure Data

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
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.
Measure Participants	51	47
Abeta42	1.5 (0.90)	0.2 (0.94)
Abeta40	8.8 (3.91)	9.7 (4.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -3.9 to 1.2
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.0
	Confidence Interval	() 95%; -10.2 to 12.2
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
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.
Measure Participants	51	47
Least Squares Mean (Standard Error) [Ratio]	-0.010 (0.0045)	-0.012 (0.0047)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.003
	Confidence Interval	(2-Sided) 95%; -0.016 to 0.010
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
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.
Measure Participants	53	47
Mean (Standard Deviation) [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
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)

Outcome Measure Data

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
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.
Measure Participants	53	53
Week 12	0.013 (0.0438)	-0.054 (0.0444)
Week 24	-0.121 (0.0445)	0.017 (0.0466)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.067
	Confidence Interval	(2-Sided) 95%; -0.191 to 0.057
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
	Parameter Dispersion	Type: Value:
	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
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)

Outcome Measure Data

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
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.
Measure Participants	55	52
Week 12	-0.062 (0.0684)	-0.125 (0.0693)
Week 24	-0.089 (0.0686)	-0.019 (0.0729)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.063
	Confidence Interval	(2-Sided) 95%; -0.257 to 0.130
	Parameter Dispersion	Type: Value:
	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo Once Daily, Rilapladib 250 mg Once Daily
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.070
	Confidence Interval	(2-Sided) 95%; -0.130 to 0.269
	Parameter Dispersion	Type: Value:
	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.

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)		1/61 (1.6%)
Serious Adverse Events
	Placebo Once Daily		Rilapladib 250mg Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/62 (8.1%)		8/61 (13.1%)
Cardiac disorders
Bradycardia	0/62 (0%)		1/61 (1.6%)
Gastrointestinal disorders
Colitis microscopic	0/62 (0%)		1/61 (1.6%)
Inguinal hernia	1/62 (1.6%)		0/61 (0%)
Large intestine perforation	1/62 (1.6%)		0/61 (0%)
Infections and infestations
Upper respiratory tract infection	1/62 (1.6%)		0/61 (0%)
Vestibular neuronitis	1/62 (1.6%)		0/61 (0%)
Injury, poisoning and procedural complications
Fall	0/62 (0%)		1/61 (1.6%)
Femoral neck fracture	0/62 (0%)		1/61 (1.6%)
Fractured coccyx	1/62 (1.6%)		0/61 (0%)
Scapula fracture	0/62 (0%)		1/61 (1.6%)
Sternal fracture	1/62 (1.6%)		0/61 (0%)
Nervous system disorders
Cerebral haemorrhage	0/62 (0%)		1/61 (1.6%)
Complex partial seizures	0/62 (0%)		1/61 (1.6%)
Dizziness	0/62 (0%)		1/61 (1.6%)
Other (Not Including Serious) Adverse Events
	Placebo Once Daily		Rilapladib 250mg Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/62 (37.1%)		16/61 (26.2%)
Gastrointestinal disorders
Nausea	5/62 (8.1%)	9	2/61 (3.3%)	2
Diarrhoea	2/62 (3.2%)	2	4/61 (6.6%)	4
Infections and infestations
Urinary tract infection	6/62 (9.7%)	7	1/61 (1.6%)	1
Cystitis	0/62 (0%)	0	4/61 (6.6%)	4
Nervous system disorders
Headache	10/62 (16.1%)	10	3/61 (4.9%)	3
Dizziness	4/62 (6.5%)	6	2/61 (3.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.