Clinical trial NCT00710684: A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease
Official title: Study AZ3110866, a Fixed Dose Study of SB-742457 Versus Placebo When Added to Existing Donepezil Treatment in Subjects With Mild-to-moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer's disease cognition SB-742457
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-07-04
Enrollment: 682
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to investigate the safety and efficacy of SB-742457 when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer's disease.


Eligibility criteria: Inclusion Criteria:

* Subjects and their caregivers must provide informed consent prior to study entry.
* Subjects must have a clinical diagnosis of probable mild-to-moderate Alzheimer's disease with no evidence of disorders that are thought to be the cause of, or contributing to the severity of the subject's dementia and a documented history of at least 6 months of ongoing donepezil therapy with stable dosing for at least the last 2 months.
* Subjects must have a regular caregiver who is willing to attend visits, oversee the subject's compliance with the study and report on the subject's status.
* Female subjects of child-bearing potential must agree to abstinence or an approved form of birth control.
* Subjects must have adequate blood pressure and laboratory values.

Exclusion Criteria:

* Subjects with a diagnosis of possible, probable or definite vascular dementia may not participate.
* Subjects with known hypersensitivity to sunlight or a history of seizures, previous exposure to SB-742457, taking agents for which there is a theoretical risk of interaction with SB-742457, or taking medication for Alzheimer's disease or centrally acting agents which might impact study outcomes may not participate.

Primary outcomes:
measure: Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24
timeFrame: Baseline(Week 0) and Week 24
measure: Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24
timeFrame: Baseline(Week 0) and Week 24
Secondary outcomes:
measure: Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48
timeFrame: Baseline (Week 0) and Week 12, 36 and 48
measure: Change From Baseline in CDR-SB Score at Week 12, 36 and 48
timeFrame: Baseline (Week 0) and Week 12, 36, 48
measure: Change From Baseline in RBANS Score at Week 12, 36 and 48
timeFrame: Baseline (Week 0) and Week 12, 36 and 48
measure: Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48
timeFrame: Baseline (Week 0) and Week 12, 24, 36 and 48
measure: Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48
timeFrame: Baseline (Week 0) and Week 24 and 48
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase
timeFrame: Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal)
measure: Number of Participants With Parameters of Clinical Concern - Hematology
timeFrame: Up to Week 48
measure: Number of Participants With Parameters of Clinical Concern - Clinical Chemistry
timeFrame: Up to Week 48
measure: Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss)
timeFrame: Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
measure: Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss)
timeFrame: Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
measure: Exposure Estimates for Donepezil (Cavgss)
timeFrame: Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
measure: Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene
timeFrame: Baseline (Week 0) to Week 24 and Week 48
measure: Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene
timeFrame: Baseline (Week 0) to Week 24 and Week 48
measure: Change From Baseline in RBANS Scale in Participants With APOE4 Gene
timeFrame: Baseline (Week 0) to Week 24 and Week 48
Other outcomes:
Locations:
city: Litchfield Park
country: United States
facility: GSK Investigational Site
state: Arizona
city: Fresno
country: United States
facility: GSK Investigational Site
state: California
city: Rancho Mirage
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Hallandale Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Hialeah
country: United States
facility: GSK Investigational Site
state: Florida
city: Manchester
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Tulsa
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Bennington
country: United States
facility: GSK Investigational Site
state: Vermont
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Cordoba
country: Argentina
facility: GSK Investigational Site
state: Córdova
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Kogarah
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Herston
country: Australia
facility: GSK Investigational Site
state: Queensland
city: Woodville
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Ballarat
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Heidelberg West
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Kew
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Saint John
country: Canada
facility: GSK Investigational Site
state: New Brunswick
city: Kentville
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Greenfield Park
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Québec
country: Canada
facility: GSK Investigational Site
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Santiago
country: Chile
facility: GSK Investigational Site
state: Región Metro De Santiago
city: Viña del Mar
country: Chile
facility: GSK Investigational Site
state: Valparaíso
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Melnik
country: Czechia
facility: GSK Investigational Site
city: Olomouc
country: Czechia
facility: GSK Investigational Site
city: Ostrava
country: Czechia
facility: GSK Investigational Site
city: Pardubice
country: Czechia
facility: GSK Investigational Site
city: Plzen
country: Czechia
facility: GSK Investigational Site
city: Praha 10
country: Czechia
facility: GSK Investigational Site
city: Praha 1
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Ellwangen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Ulm
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Alzenau
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Guenzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Regensburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Unterhaching
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Bad Homburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Schwerin
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Schwerin
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Achim
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Aachen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bad Honnef
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Jena
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Chieti Scalo
country: Italy
facility: GSK Investigational Site
state: Abruzzo
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: San Felice A Cancello - Caserta
country: Italy
facility: GSK Investigational Site
state: Campania
city: Cassino (FR)
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Brescia
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Castellanza (VA)
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Milano
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Rho
country: Italy
facility: GSK Investigational Site
state: Lombardia
city: Torino
country: Italy
facility: GSK Investigational Site
state: Piemonte
city: Lido Di Camaiore (LU)
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Pisa
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Perugia
country: Italy
facility: GSK Investigational Site
state: Umbria
city: Valdagno (VI)
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Verona
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Baracaldo/Vizcaya
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Burgos
country: Spain
facility: GSK Investigational Site
city: Castellón
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Murcia
country: Spain
facility: GSK Investigational Site
city: Salamanca
country: Spain
facility: GSK Investigational Site
city: San Sebastián
country: Spain
facility: GSK Investigational Site
city: San Vicente Del Raspeig/Alicante
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Maher-Edwards G, Watson C, Ascher J, Barnett C, Boswell D, Davies J, Fernandez M, Kurz A, Zanetti O, Safirstein B, Schronen JP, Zvartau-Hind M, Gold M. Two randomized controlled trials of SB742457 in mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2015 May 7;1(1):23-36. doi: 10.1016/j.trci.2015.04.001. eCollection 2015 Jun.