Open-Label Extension Study Of Rosiglitazone XR As Adjunctive Therapy In Subjects With Mild-to-Moderate Alzheimers

Alzheimer's Disease Clinical Trial

Official title:

An Open-label Extension to Study AVA102670 and AVA102672, to Assess the Long-term Safety and Efficacy of Rosiglitazone (Extended Release Tablets) as Adjunctive Therapy on Cognition in Subjects With Mild to Moderate Alzheimer's Disease.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00490568
• Other study ID #: AVA102675
• Status: Terminated
• Phase: Phase 3
• First received: June 21, 2007
• Last updated: October 11, 2017
• Start date: August 8, 2007
• Est. completion date: June 1, 2009

Study information

• Verified date: September 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase III, multicenter, open-label extension, single-group study in male and female outpatients with mild-to-moderate Alzheimer's disease (AD) who have completed either AVA102670 or AVA102672. All subjects will receive rosiglitazone extended-release (RSG XR) 4mg once daily for the first 4 weeks of the study followed by 8mg RSG XR as adjunctive therapy to their existing dose of acetylcholinesterase inhibitor. Subject participation will last until one of 5 conditions applies. After a 52-week open-label treatment phase, subjects will attend a final Follow-Up Visit 6 weeks after the end of treatment. The primary objective of this study is to evaluate the long-term safety and tolerability of RSG XR in subjects with mild-to-moderate AD who have completed either AVA102670 or AVA102672. The secondary objective of this study is to explore further the long-term efficacy of RSG XR in terms of cognitive function and overall clinical response as a function of apolipoprotein E (APOE) e4 allele status.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1461
• Est. completion date: June 1, 2009
• Est. primary completion date: June 1, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 51 Years to 91 Years

Eligibility

Inclusion criteria:

• Successful completion of AVA102670 or AVA102672 without safety or tolerability issues. Regular caregiver.

Exclusion criteria:

• Congestive Heart Failure (NYHA 1-4), clinically significant peripheral edema, other neurological conditions that might disqualify participation. SAE, clinically significant laboratory abnormality or significant cardiovascular event during prior study.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Rosiglitazone XR
Experimental drug

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Cordoba	Córdova
Argentina	GSK Investigational Site	Córdoba	Córdova
Argentina	GSK Investigational Site	Córdoba	Córdova
Argentina	GSK Investigational Site	Godoy Cruz	Mendoza
Argentina	GSK Investigational Site	Mendoza
Australia	GSK Investigational Site	Auchenflower	Queensland
Australia	GSK Investigational Site	Cheltenham	Victoria
Australia	GSK Investigational Site	Chermside	Queensland
Australia	GSK Investigational Site	Heidelberg Heights	Victoria
Australia	GSK Investigational Site	Hornsby	New South Wales
Australia	GSK Investigational Site	Kew	Victoria
Australia	GSK Investigational Site	Kippa Ring	Queensland
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	Randwick	New South Wales
Australia	GSK Investigational Site	Woodville	South Australia
Austria	GSK Investigational Site	Hall in Tirol
Austria	GSK Investigational Site	Vienna
Austria	GSK Investigational Site	Vienna
Austria	GSK Investigational Site	Vienna
Austria	GSK Investigational Site	Vienna
Belgium	GSK Investigational Site	Kortrijk
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Woluwe-Saint-Lambert
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Varna
Canada	GSK Investigational Site	Charlottetown	Prince Edward Island
Canada	GSK Investigational Site	Greenfield Park	Quebec
Canada	GSK Investigational Site	Kentville	Nova Scotia
Canada	GSK Investigational Site	Kingston	Ontario
Canada	GSK Investigational Site	Kingston	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Peterborough	Ontario
Canada	GSK Investigational Site	Québec
Canada	GSK Investigational Site	Regina	Saskatchewan
Canada	GSK Investigational Site	Saint John	New Brunswick
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Whitby	Ontario
Chile	GSK Investigational Site	Providencia / Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Viña del Mar	Valparaíso
Czechia	GSK Investigational Site	Olomouc
Czechia	GSK Investigational Site	Ostrava
Czechia	GSK Investigational Site	Praha 10
Czechia	GSK Investigational Site	Praha 2
Czechia	GSK Investigational Site	Praha 5
Czechia	GSK Investigational Site	Praha 7
Czechia	GSK Investigational Site	Praha 8
Czechia	GSK Investigational Site	Trutnov
Finland	GSK Investigational Site	Helsinki
Finland	GSK Investigational Site	Kuopio
France	GSK Investigational Site	Bourg en Bresse
France	GSK Investigational Site	Caen
France	GSK Investigational Site	Dijon
France	GSK Investigational Site	Ivry
France	GSK Investigational Site	La Seyne sur Mer
France	GSK Investigational Site	Lille
France	GSK Investigational Site	Limoges
France	GSK Investigational Site	Luynes
France	GSK Investigational Site	Lyon
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Metz
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Nantes
France	GSK Investigational Site	Nice
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Pau
France	GSK Investigational Site	Rodez
France	GSK Investigational Site	Saint Ouen la Rouerie
France	GSK Investigational Site	Saint-Etienne
France	GSK Investigational Site	Sautron
France	GSK Investigational Site	Tinteniac
France	GSK Investigational Site	Toulon
France	GSK Investigational Site	Toulouse
France	GSK Investigational Site	Tours
France	GSK Investigational Site	Vichy
Germany	GSK Investigational Site	Aalen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Achim	Niedersachsen
Germany	GSK Investigational Site	Alzenau	Bayern
Germany	GSK Investigational Site	Bad Homburg	Hessen
Germany	GSK Investigational Site	Bad Honnef	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bad Saarow	Brandenburg
Germany	GSK Investigational Site	Baesweiler	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bergisch Gladbach	Nordrhein-Westfalen
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bockhorn	Niedersachsen
Germany	GSK Investigational Site	Chemnitz	Sachsen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Dueren	Nordrhein-Westfalen
Germany	GSK Investigational Site	Duisburg	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ellwangen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Erbach	Hessen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ganderkesee	Niedersachsen
Germany	GSK Investigational Site	Gera	Thueringen
Germany	GSK Investigational Site	Goettingen	Niedersachsen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Hattingen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Juelich	Nordrhein-Westfalen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Krefeld	Nordrhein-Westfalen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Ludwigsburg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Lueneburg	Niedersachsen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Nuernberg	Bayern
Germany	GSK Investigational Site	Ostfildern	Baden-Wuerttemberg
Germany	GSK Investigational Site	Regensburg	Bayern
Germany	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Siegen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Germany	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Ulm	Baden-Wuerttemberg
Germany	GSK Investigational Site	Unterhaching	Bayern
Germany	GSK Investigational Site	Westerstede	Niedersachsen
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Melissia
Greece	GSK Investigational Site	Thessaloniki
Hong Kong	GSK Investigational Site	Hong Kong
Hong Kong	GSK Investigational Site	Shatin
Hungary	GSK Investigational Site	Gyor
Hungary	GSK Investigational Site	Szeged
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Nagpur
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Varanasi
Italy	GSK Investigational Site	Arezzo	Toscana
Italy	GSK Investigational Site	Brescia	Lombardia
Italy	GSK Investigational Site	Chieti Scalo	Abruzzo
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Pavia	Lombardia
Italy	GSK Investigational Site	Pisa	Toscana
Italy	GSK Investigational Site	Rho	Lombardia
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	San Felice a Cancello Caserta	Campania
Italy	GSK Investigational Site	Torrette (AN)	Marche
Korea, Republic of	GSK Investigational Site	Seongnam-si,
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Netherlands	GSK Investigational Site	Alkmaar
Netherlands	GSK Investigational Site	Blaricum
Netherlands	GSK Investigational Site	Den Bosch
Netherlands	GSK Investigational Site	Den Haag
Netherlands	GSK Investigational Site	Hengelo
Netherlands	GSK Investigational Site	Hilversum
Philippines	GSK Investigational Site	Pasig City
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Mosina
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Sopot
Poland	GSK Investigational Site	Warsaw
Portugal	GSK Investigational Site	Coimbra
Portugal	GSK Investigational Site	Lisboa
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Kosice
Slovenia	GSK Investigational Site	Šempeter
Slovenia	GSK Investigational Site	Ljubljana
South Africa	GSK Investigational Site	Loeventstein
South Africa	GSK Investigational Site	Oakdale
South Africa	GSK Investigational Site	Richards Bay
South Africa	GSK Investigational Site	Rosebank
South Africa	GSK Investigational Site	Somerset West
South Africa	GSK Investigational Site	Waverley, Bloemfontein
South Africa	GSK Investigational Site	Willows, X14, Pretoria
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Burgos
Spain	GSK Investigational Site	Castellón
Spain	GSK Investigational Site	Elche (Alicante)
Spain	GSK Investigational Site	Gerona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Murcia
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Tarrasa, Barcelona
Spain	GSK Investigational Site	Valencia
Sweden	GSK Investigational Site	Jönköping
Sweden	GSK Investigational Site	Kalix
Sweden	GSK Investigational Site	Mölndal
Sweden	GSK Investigational Site	Sundsvall
Sweden	GSK Investigational Site	Umeå
United Kingdom	GSK Investigational Site	Blackpool	Lancashire
United Kingdom	GSK Investigational Site	Bradford
United Kingdom	GSK Investigational Site	Liverpool
United Kingdom	GSK Investigational Site	West of Scotland Science Park, Glasgow
United States	GSK Investigational Site	Albany	New York
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bennington	Vermont
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Deerfield Beach	Florida
United States	GSK Investigational Site	Delray Beach	Florida
United States	GSK Investigational Site	Fort Wayne	Indiana
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Hialeah	Florida
United States	GSK Investigational Site	Litchfield Park	Arizona
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Morristown	New Jersey
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Norwalk	Connecticut
United States	GSK Investigational Site	Ocala	Florida
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Providence	Rhode Island
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Rancho Mirage	California
United States	GSK Investigational Site	Rockville	Maryland
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Saint Paul	Minnesota
United States	GSK Investigational Site	Saint Petersburg	Florida
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Sherman Oaks	California
United States	GSK Investigational Site	South Ogden	Utah
United States	GSK Investigational Site	Springfield	Massachusetts
United States	GSK Investigational Site	Stratford	New Jersey
United States	GSK Investigational Site	Syracuse	New York
United States	GSK Investigational Site	Toledo	Ohio
United States	GSK Investigational Site	Toms River	New Jersey
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Tulsa	Oklahoma
United States	GSK Investigational Site	West Palm Beach	Florida
United States	GSK Investigational Site	West Yarmouth	Massachusetts
United States	GSK Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Chile,  Czechia,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Philippines,  Poland,  Portugal,  Slovakia,  Slovenia,  South Africa,  Spain,  Sweden,  United Kingdom, 

References & Publications (1)

Harrington C, Sawchak S, Chiang C, Davies J, Donovan C, Saunders AM, Irizarry M, Jeter B, Zvartau-Hind M, van Dyck CH, Gold M. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer's disease: two phase 3 studies. Curr Alzheimer Res. 2011 Aug;8(5):592-606. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Any Adverse Events (AEs) and Severity of AEs	An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The severity of the AE'S was categorized as mild, moderate and severe. Number of participants reporting AEs during the on treatment phase of the study.	Up to 76 Weeks
Secondary	Number Participants With Serious Adverse Events (SAEs) and Deaths	A SAE is defined as any untoward medical occurrence that, at any dose results in death, is a life-threatening condition, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, or a congenital anomaly or birth defect. Number of participants with SAEs and deaths were reported for treatment duration of the study.	Up to 76 Weeks
Secondary	Number of Participants With Adverse Event of Oedema	Oedema was considered as adverse event of special interest (AESI). The process for AESI selection was based on RSG's pharmacologic class and relevant AEs potentially associated with RSG. The number of participants and their percentage for the adverse event of the various types of oedema were reported.	Up to 76 Weeks
Secondary	Change From Baseline in Vital Sign Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Vital signs SBP and DBP were measured at each visit. All measurements were made on the participant non-dominant arm supported at heart level, using the same cuff size and same equipment. Blood pressure was measured once, after the participant sat quietly for at least 5 minutes. DBP was measured at the disappearance of Korotkoff sounds (Phase V). If the participant was a smoker or used tobacco products, a period of 30 minutes without tobacco was allowed before taking these measurements. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the blood pressure value recorded at specified visit minus the Baseline value.	Up to 70 Weeks (including follow up)
Secondary	Change From Baseline in Vital Sign Heart Rate (HR)	Vital sign HR was measured at each visit. HR was measured once, after the participant sat quietly for at least 5 minutes. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the HR at specified visit minus the Baseline value.	Up to 70 Weeks (including follow up)
Secondary	Change From Baseline in Vital Sign Body Weight (BW)	BW was measured at all visits, without shoes and wearing light clothing. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the body weight at specified visit minus the Baseline value.	Up to 70 Weeks (including follow up)
Secondary	Change From Baseline in Non-fasting Measures of Lipid Metabolism Namely Total Cholesterol (TC), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), Triglycerides	The clinical chemistry data included non-fasting measures of lipid metabolism (TC,HDL,LDL,triglycerides). Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication. Change from Baseline was measured as the lipids (TC,HDL,LDL,triglycerides) value recorded at specified visit minus the Baseline value.	Up to 82 Weeks (including follow up)
Secondary	Number of Participants With SBP and DBP Values of Potential Clinical Concern (PCC)	The frequency of participant vital sign sitting blood pressure was obtained to check if the values lie outside of a pre-determined reference range (RR) for SBP 90-140 mmHg, DBP 50-90 mmHg or have a change from Baseline of PCC for SBP increase from Baseline (IFB) >=40, decrease from Baseline (DFB) >= 30 for and for DBP (IFB) >= 30 ,DFB >= 20. The number of participants with values of PCC at any time on treatment (ATOT) and follow up were reported.	Up to 70 Weeks (including follow up)
Secondary	Number of Participants With HR Values of PCC ATOT	HR was measured once, after the participant sat quietly for at least 5 minutes. The frequency of participant vital sign heart rate was obtained to check if the values lie outside of a pre-determined reference range (RR) 50-100 bpm or have a change from Baseline of PCC IFB >=30 and DFB >=30. The number of participants with values of PCC including follow up were reported.	Up to 70 Weeks (including follow up)
Secondary	Number of Participants With BW Values of PCC ATOT	The frequency of participant vital sign weight was obtained to check if the values have CFB of PCC IFB >=7 percent. With the exception of Week 4, when participants were first titrated to the 8mg RSG XR dose, at every time point in the study where weight was measured the percentage of participants experienced an increase in BW of PCC was approximately 2 times greater than the percentage of participants experiencing an decrease in BW of PCC DFB >=7 percent. The number of participants with values of PCC including follow up were reported.	Up to 70 Weeks (including follow up)
Secondary	Number of Participants With Hematology Parameters of PCC ATOT	The hematology data included eosinophils, haematocrit, haemoglobin, lymphocytes, mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), monocytes, platelet count, red cell distribution width (RDW), red blood cell (RBC) count, segmented neutrophils (SN), total neutrophils (TN), white blood cell (WBC) count. The number of participants with values of PCC (defined as high and low) ATOT were reported.	Up to Week 82 (including follow up)
Secondary	Number of Participants With Clinical Chemistry Parameters (Including Lipids) of PCC ATOT	The clinical chemistry data included alanine amino transferase (ALT), albumin, aldolase, asparatate amino transferase (AST), BUN/creatinine ratio, carbon dioxide(CO2) content, chloride, cholesterol, creatinine kinase (CK), creatinine, direct bilirubin (DB), gamma glutamyl transferase (GGT), glucose, glycosylated Hemoglobin (HbA1C), HDL, LDL, lactate dehydrogenase (LD), magnesium, potassium, sodium, total bilirubin (TB), triglycerides, troponin I, urea. The number of participants with values of PCC (defined as high and low) ATOT were reported.	Up to Week 82 (including follow up)
Secondary	Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Total Score as a Function of Apolipoprotein E (APOE) e4 Status.	The 11-item ADAS-Cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.	Baseline (Week 0) and Week 24, 52
Secondary	Change From Baseline in Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) Score as a Function of APOE e4 Status.	The CDR-SB is a validated clinical assessment of global function in par. with Alzheimer's disease (AD). Impairment was scored in each of 6 cognitive categories on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2, and severe = 3. The 6 individual category ratings, or box scores, were added together to give the CDR-Sum of Boxes which ranged from 0 to 18 (severe impairment). Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.	Baseline (Week 0) and Week 24, 52
Secondary	Change From Baseline in Mini Mental State Examination (MMSE) Total Score as a Function of APOE e4 Status.	The MMSE consisted of 11 tests of orientation, memory (recent and immediate), concentration, language and praxis. Scores ranged from 0 to 30, with lower scores indicating greater cognitive impairment. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.	Baseline (Week 0) and Week 24, 52
Secondary	Change From Baseline in Disability Assessment for Dementia Scale (DAD) Total Score as a Function of APOE e4 Status.	DAD, assessed the ability of a participant to execute basic and instrumental activities of daily living (ADL) and leisure activities. The scale consists of 40 questions assessing basic and instrumental ADLs. This scale assesses a participant's ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item was scored as yes: 1, no: 0 and N/A: not applicable. Higher scores indicate less disability with a score of 100 indicating no disability and 0 indicating no functional ability. The percentage score was calculated as (DAD total score/total number of applicable items) * 100. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.	Baseline (Week 0) and Week 24, 52
Secondary	Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score as a Function of APOE e4 Status.	12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor disturbance, appetite, nighttime behavior. A screening question is asked about each sub-domain. If the responses to these questions=participant has problems with a particular sub-domain of behavior, the caregiver asked all the questions about that domain, rating the frequency (1=occasionally to 4=very frequently) on a 4-point scale, their severity (1=Mild to 3=Severe) on a 3-point scale, and the distress on a 5-point scale. Total score=sum of each domain score(range 0-144);higher score=greater behavioral disturbances. Baseline for the open-label study was the latest assessment from Week 48 of parent studies to the first dose of open-label medication (Week 0). Change from Baseline was calculated as the Baseline value minus the value at the specified time point.	Baseline (Week 0) and Week 24, 52

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