Clinical trial NCT00708552: Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's Disease
Official title: Study AZ3110865, a Study Comparing SB-742457 or Donepezil Versus Placebo 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: 2008-07-02
Enrollment: 576
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 efficacy, safety and tolerability of SB-742457 versus placebo in subjects with mild-to-moderate Alzheimer's disease. SB-742457 is an experimental treatment which increases the levels of certain chemicals in the brain that are often decreased in patients with 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 a documented 6-month history of AD symptoms
* 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 pregnancy testing and approved form of birth control.

Exclusion criteria:

* Diagnosis of possible, probable or definite vascular dementia.
* History/evidence of any other CNS disorder that could be interpreted as a cause of dementia
* History of known or suspected seizures, loss of consciousness or significant head trauma
* Subjects with ECG, blood pressure and laboratory values outside of protocol criteria are excluded.
* Subjects with known photosensitivity
* Subjects with a history of 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: Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score at Week 24
timeFrame: 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: Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline Mini Mental State Examination [MMSE] Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline [MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in ADAS-Cog Total Score at Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: CIBIC+ Score at Week 12
timeFrame: Week 12
measure: Change From Baseline in RBANS Total Score at Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12
timeFrame: Baseline (Week 0) and Week 12
measure: Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 12
timeFrame: Week 12
measure: Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 12
timeFrame: Week 12
measure: Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score at Weeks 12 and 24
timeFrame: Baseline (Week 0) and Weeks 12 and 24
measure: Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) Total Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in MMSE Total Score at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24
timeFrame: Baseline (Week 0) and Weeks 12 and 24
measure: Number of Participants With Any Adverse Event (Serious and Non-serious) and Serious Adverse Events (SAEs)
timeFrame: Upto Week 24
measure: Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT)
timeFrame: Upto Week 24
measure: Number of Participants With Hematology Data of PCC ATOT
timeFrame: Upto Week 24
measure: Number of Participants With Chemistry Data of PCC ATOT
timeFrame: Upto Week 24
measure: Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Clinical Chemistry Parameter Blood Urea Nitrogen /Creatinine Ratio at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Clinical Chemistry Parameters Creatinine, Direct Bilirubin and Total Bilirubin at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Hematology Parameter Hematocrit
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Hematology Parameters Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Hematology Parameter Mean Corpuscle Volume and Mean Platelet Volume at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Change From Baseline in Hematology Parameter Red Blood Cell Count at Week 24
timeFrame: Baseline (Week 0) and Week 24
measure: Number of Participants With Electrocardiogram (ECG) Findings as Assessed by Investigator and Central Cardiologist
timeFrame: Upto Week 24
measure: Exposure Estimates for SB-742457 Area Under Curve Over the Dosing Interval at Steady State (AUCτss)
timeFrame: One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose
measure: Exposure Estimates for SB-742457 Minimum Concentration at Steady State (Cmin-ss)
timeFrame: One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose
measure: Exposure Estimates for Donepezil Average Concentration at Steady State (Cavgss)
timeFrame: Weeks 4, 8,12,18 and Week 24
Other outcomes:
Locations:
city: Shumen
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Varna
country: Bulgaria
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: Brno
country: Czechia
facility: GSK Investigational Site
city: Olomouc
country: Czechia
facility: GSK Investigational Site
city: Praha 10
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 2
country: Czechia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tartu
country: Estonia
facility: GSK Investigational Site
city: Stuttgart
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tuebingen
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Neuburg / Donau
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Nuernberg
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: Erbach
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Huettenberg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Achim
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dueren
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Duisburg
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Hattingen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Siegen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Melissia
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Busan
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Aguascalientes, Ags
country: Mexico
facility: GSK Investigational Site
state: Aguascalientes
city: Tijuana
country: Mexico
facility: GSK Investigational Site
state: Baja California Norte
city: Saltillo
country: Mexico
facility: GSK Investigational Site
state: Coahuila
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Mexico, D.F.
country: Mexico
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Bydgoszcz
country: Poland
facility: GSK Investigational Site
city: Mosina
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
city: Sopot
country: Poland
facility: GSK Investigational Site
city: Warsaw
country: Poland
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: St.-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Durban
country: South Africa
facility: GSK Investigational Site
city: Loeventstein
country: South Africa
facility: GSK Investigational Site
city: Oakdale
country: South Africa
facility: GSK Investigational Site
city: Pretoria
country: South Africa
facility: GSK Investigational Site
city: Rosebank
country: South Africa
facility: GSK Investigational Site
city: Sunninghill
country: South Africa
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.