search
Back to results

A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SB-742457 15mg
SB-742457 35mg
Placebo
donepezil 5-10mg
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's disease cognition SB-742457

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

DONEPEZIL + SB-742457 15 MG

DONEPEZIL + PLACEBO

DONEPEZIL + SB-742457 35 MG

Arm Description

SB-742457 - 15mg added to existing donepezil treatment

Placebo added to existing donepezil

SB-742457 - 35mg added to existing donepezil

Outcomes

Primary Outcome Measures

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24
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. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the case report form (CRF) for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean is presented.
Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24
The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored 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 ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

Secondary Outcome Measures

Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24
RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48
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. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the CRF for questions 3 to 6 and 8 to 11. In cases where more than one question was missing, a total score was not be imputed. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been present
Change From Baseline in CDR-SB Score at Week 12, 36 and 48
The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored 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 ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Change From Baseline in RBANS Score at Week 12, 36 and 48
RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
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
The ADCS-ADL is an interviewer-administered informant-based scale where the informant (caregiver) responds to 23 activities of daily living questions about the participant. The questions ranged from basic to instrumental activities of daily living and take approximately 20 minutes to complete. The Total score ranges from 0-78 and a higher score signified greater functional ability. The questionnaire was split into two types of questions, an initial question relating to whether a participant had completed a particular activity and then a follow on question which scored how much assistance the participant had required if they had performed that particular activity. The total score was calculated by adding up the responses for each of the individual activities. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48
The MMSE consisted of 11 items covering orientation, memory (recent and immediate), concentration, language and praxis. Scores ranged from 0 to 30, with lower scores indicating greater cognitive impairment. Scores for each of the 11 individual tests were not recorded on the CRF, therefore if any item was missing then the total score was be set to missing. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Number of Participants With Parameters of Clinical Concern - Hematology
Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Eosinophils (high-2), Hematocrit (low- 0.8, high-1.2), Lymphocytes (low-0.75, high-1.5), Mean Corpuscle Hemoglobin (MCH) (low-0.8, high-1.2), Monocytes(low-0.75, high-2), Neutrophil bands (high-10), Platelet count (low-100, high-500), Segmented Neutrophils (low-0.75, high-1.3), Total Neutrophils (low-0.75, high-1.5), and white blood cells (WBC) (low-3, high-15).
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry
Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Alanine Amino Transferase (ALT) (high-1.5), Alkaline Phosphatase (high-1.5), Aspartate Amino Transferase (ASAT) (high-1.5), BUN/Creatinine ratio (high-1.5), Calcium (low- 0.75, high-1.25), Carbon dioxide content/Bicarbonate (low-15, high- 40), Cholesterol (high-1.25), Creatine Kinase ((low- 0.5, high-1.25), Creatinine (low- 0.5, high-1.25), Direct Bilirubin (high-1.5), Gamma Glutamyl Transferase (GGT) (high-2), Glucose (low- 3.6, high-7.8), HDL Cholesterol (low-0.65), LDL Cholesterol (hig-1.25), Magnesium (low-0.5, high-2), Phosphorus inorganic (low- 0.5, high-1.5), Potassium (low- 3, high-5.5), Sodium (low- 130, high-150), Total Bilirubin (high-1.5), Triglycerides (high -4) and Urea/BUN (high-11).
Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss)
AUCτss of SB-742457 was estimated via nonlinear mixed effect analysis. This pharmacokinetic(PK) model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.
Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss)
Cmin-ss was estimated via nonlinear mixed effect analysis. This PK model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.
Exposure Estimates for Donepezil (Cavgss)
Participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) were allowed to participate in this study. Cavgss for donepezil approximately 12 to 20 hours after dosing were summarized by donepezil dose level 5 mg/7.5 mg/10 mg/15 mg.
Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene
Genetic analyses was conducted to assess the effect of APOE4 carriage. 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. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores were recorded on the CRF for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.
Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene
Genetic analyses was conducted to assess the effect of APOE4 carriage. The CDR-SB is an interviewer administered scale and impairment is scored in following categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment was scored 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 ranges from 0-18, with higher score indicating severe impairment. If there were any missing items then CDR-SB was set to missing and was not imputed. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.
Change From Baseline in RBANS Scale in Participants With APOE4 Gene
Genetic analyses was conducted to assess the effect of APOE4 carriage. RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.

Full Information

First Posted
June 30, 2008
Last Updated
November 3, 2017
Sponsor
GlaxoSmithKline
search

1. Study Identification

Unique Protocol Identification Number
NCT00710684
Brief Title
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

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
July 1, 2008 (Actual)
Primary Completion Date
May 21, 2010 (Actual)
Study Completion Date
November 16, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Alzheimer's disease cognition SB-742457

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
682 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DONEPEZIL + SB-742457 15 MG
Arm Type
Experimental
Arm Description
SB-742457 - 15mg added to existing donepezil treatment
Arm Title
DONEPEZIL + PLACEBO
Arm Type
Placebo Comparator
Arm Description
Placebo added to existing donepezil
Arm Title
DONEPEZIL + SB-742457 35 MG
Arm Type
Experimental
Arm Description
SB-742457 - 35mg added to existing donepezil
Intervention Type
Drug
Intervention Name(s)
SB-742457 15mg
Intervention Description
SB-742457 - 15mg added to existing donepezil treatment
Intervention Type
Drug
Intervention Name(s)
SB-742457 35mg
Intervention Description
SB-742457 - 35mg added to existing donepezil
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo added to existing donepezil
Intervention Type
Drug
Intervention Name(s)
donepezil 5-10mg
Intervention Description
existing donepezil treatment
Primary Outcome Measure Information:
Title
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24
Description
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. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the case report form (CRF) for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean is presented.
Time Frame
Baseline(Week 0) and Week 24
Title
Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24
Description
The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored 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 ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame
Baseline(Week 0) and Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24
Description
RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame
Baseline (Week 0) and Week 24
Title
Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48
Description
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. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the CRF for questions 3 to 6 and 8 to 11. In cases where more than one question was missing, a total score was not be imputed. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been present
Time Frame
Baseline (Week 0) and Week 12, 36 and 48
Title
Change From Baseline in CDR-SB Score at Week 12, 36 and 48
Description
The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored 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 ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame
Baseline (Week 0) and Week 12, 36, 48
Title
Change From Baseline in RBANS Score at Week 12, 36 and 48
Description
RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame
Baseline (Week 0) and Week 12, 36 and 48
Title
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
Description
The ADCS-ADL is an interviewer-administered informant-based scale where the informant (caregiver) responds to 23 activities of daily living questions about the participant. The questions ranged from basic to instrumental activities of daily living and take approximately 20 minutes to complete. The Total score ranges from 0-78 and a higher score signified greater functional ability. The questionnaire was split into two types of questions, an initial question relating to whether a participant had completed a particular activity and then a follow on question which scored how much assistance the participant had required if they had performed that particular activity. The total score was calculated by adding up the responses for each of the individual activities. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame
Baseline (Week 0) and Week 12, 24, 36 and 48
Title
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48
Description
The MMSE consisted of 11 items covering orientation, memory (recent and immediate), concentration, language and praxis. Scores ranged from 0 to 30, with lower scores indicating greater cognitive impairment. Scores for each of the 11 individual tests were not recorded on the CRF, therefore if any item was missing then the total score was be set to missing. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame
Baseline (Week 0) and Week 24 and 48
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase
Description
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Time Frame
Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal)
Title
Number of Participants With Parameters of Clinical Concern - Hematology
Description
Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Eosinophils (high-2), Hematocrit (low- 0.8, high-1.2), Lymphocytes (low-0.75, high-1.5), Mean Corpuscle Hemoglobin (MCH) (low-0.8, high-1.2), Monocytes(low-0.75, high-2), Neutrophil bands (high-10), Platelet count (low-100, high-500), Segmented Neutrophils (low-0.75, high-1.3), Total Neutrophils (low-0.75, high-1.5), and white blood cells (WBC) (low-3, high-15).
Time Frame
Up to Week 48
Title
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry
Description
Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Alanine Amino Transferase (ALT) (high-1.5), Alkaline Phosphatase (high-1.5), Aspartate Amino Transferase (ASAT) (high-1.5), BUN/Creatinine ratio (high-1.5), Calcium (low- 0.75, high-1.25), Carbon dioxide content/Bicarbonate (low-15, high- 40), Cholesterol (high-1.25), Creatine Kinase ((low- 0.5, high-1.25), Creatinine (low- 0.5, high-1.25), Direct Bilirubin (high-1.5), Gamma Glutamyl Transferase (GGT) (high-2), Glucose (low- 3.6, high-7.8), HDL Cholesterol (low-0.65), LDL Cholesterol (hig-1.25), Magnesium (low-0.5, high-2), Phosphorus inorganic (low- 0.5, high-1.5), Potassium (low- 3, high-5.5), Sodium (low- 130, high-150), Total Bilirubin (high-1.5), Triglycerides (high -4) and Urea/BUN (high-11).
Time Frame
Up to Week 48
Title
Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss)
Description
AUCτss of SB-742457 was estimated via nonlinear mixed effect analysis. This pharmacokinetic(PK) model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.
Time Frame
Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
Title
Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss)
Description
Cmin-ss was estimated via nonlinear mixed effect analysis. This PK model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.
Time Frame
Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
Title
Exposure Estimates for Donepezil (Cavgss)
Description
Participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) were allowed to participate in this study. Cavgss for donepezil approximately 12 to 20 hours after dosing were summarized by donepezil dose level 5 mg/7.5 mg/10 mg/15 mg.
Time Frame
Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48
Title
Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene
Description
Genetic analyses was conducted to assess the effect of APOE4 carriage. 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. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores were recorded on the CRF for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.
Time Frame
Baseline (Week 0) to Week 24 and Week 48
Title
Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene
Description
Genetic analyses was conducted to assess the effect of APOE4 carriage. The CDR-SB is an interviewer administered scale and impairment is scored in following categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment was scored 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 ranges from 0-18, with higher score indicating severe impairment. If there were any missing items then CDR-SB was set to missing and was not imputed. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.
Time Frame
Baseline (Week 0) to Week 24 and Week 48
Title
Change From Baseline in RBANS Scale in Participants With APOE4 Gene
Description
Genetic analyses was conducted to assess the effect of APOE4 carriage. RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.
Time Frame
Baseline (Week 0) to Week 24 and Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Litchfield Park
State/Province
Arizona
ZIP/Postal Code
85340
Country
United States
Facility Name
GSK Investigational Site
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
GSK Investigational Site
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
Facility Name
GSK Investigational Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94109
Country
United States
Facility Name
GSK Investigational Site
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Facility Name
GSK Investigational Site
City
Hialeah
State/Province
Florida
ZIP/Postal Code
33016
Country
United States
Facility Name
GSK Investigational Site
City
Manchester
State/Province
New Jersey
ZIP/Postal Code
08759
Country
United States
Facility Name
GSK Investigational Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
GSK Investigational Site
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
GSK Investigational Site
City
Tulsa
State/Province
Oklahoma
ZIP/Postal Code
74104
Country
United States
Facility Name
GSK Investigational Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
GSK Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78757
Country
United States
Facility Name
GSK Investigational Site
City
Bennington
State/Province
Vermont
ZIP/Postal Code
05201
Country
United States
Facility Name
GSK Investigational Site
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1022AAO
Country
Argentina
Facility Name
GSK Investigational Site
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1405BCH
Country
Argentina
Facility Name
GSK Investigational Site
City
Ciudad de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1431FWO
Country
Argentina
Facility Name
GSK Investigational Site
City
La Plata
State/Province
Buenos Aires
ZIP/Postal Code
B1900AVG
Country
Argentina
Facility Name
GSK Investigational Site
City
Cordoba
State/Province
Córdova
ZIP/Postal Code
5000
Country
Argentina
Facility Name
GSK Investigational Site
City
Buenos Aires
ZIP/Postal Code
1425
Country
Argentina
Facility Name
GSK Investigational Site
City
Santa Fe
ZIP/Postal Code
3000
Country
Argentina
Facility Name
GSK Investigational Site
City
Kogarah
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Facility Name
GSK Investigational Site
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
GSK Investigational Site
City
Woodville
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Facility Name
GSK Investigational Site
City
Ballarat
State/Province
Victoria
ZIP/Postal Code
3350
Country
Australia
Facility Name
GSK Investigational Site
City
Heidelberg West
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
GSK Investigational Site
City
Kew
State/Province
Victoria
ZIP/Postal Code
3101
Country
Australia
Facility Name
GSK Investigational Site
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
GSK Investigational Site
City
Saint John
State/Province
New Brunswick
ZIP/Postal Code
E2L 3L6
Country
Canada
Facility Name
GSK Investigational Site
City
Kentville
State/Province
Nova Scotia
ZIP/Postal Code
B4N 4K9
Country
Canada
Facility Name
GSK Investigational Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1G 4G3
Country
Canada
Facility Name
GSK Investigational Site
City
Peterborough
State/Province
Ontario
ZIP/Postal Code
K9H 2P4
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3B 2S7
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6M 3Z5
Country
Canada
Facility Name
GSK Investigational Site
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2J2
Country
Canada
Facility Name
GSK Investigational Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
GSK Investigational Site
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 1Z1
Country
Canada
Facility Name
GSK Investigational Site
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1J 3H5
Country
Canada
Facility Name
GSK Investigational Site
City
Québec
ZIP/Postal Code
G1R 3X5
Country
Canada
Facility Name
GSK Investigational Site
City
Santiago
State/Province
Región Metro De Santiago
ZIP/Postal Code
7510186
Country
Chile
Facility Name
GSK Investigational Site
City
Santiago
State/Province
Región Metro De Santiago
ZIP/Postal Code
7560356
Country
Chile
Facility Name
GSK Investigational Site
City
Viña del Mar
State/Province
Valparaíso
ZIP/Postal Code
252-0997
Country
Chile
Facility Name
GSK Investigational Site
City
Santiago
Country
Chile
Facility Name
GSK Investigational Site
City
Melnik
ZIP/Postal Code
27601
Country
Czechia
Facility Name
GSK Investigational Site
City
Olomouc
ZIP/Postal Code
775 20
Country
Czechia
Facility Name
GSK Investigational Site
City
Ostrava
ZIP/Postal Code
702 00
Country
Czechia
Facility Name
GSK Investigational Site
City
Pardubice
ZIP/Postal Code
53203
Country
Czechia
Facility Name
GSK Investigational Site
City
Plzen
ZIP/Postal Code
301 00
Country
Czechia
Facility Name
GSK Investigational Site
City
Praha 10
ZIP/Postal Code
10000
Country
Czechia
Facility Name
GSK Investigational Site
City
Praha 1
ZIP/Postal Code
110 00
Country
Czechia
Facility Name
GSK Investigational Site
City
Praha 4
ZIP/Postal Code
14059
Country
Czechia
Facility Name
GSK Investigational Site
City
Ellwangen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
73479
Country
Germany
Facility Name
GSK Investigational Site
City
Stuttgart
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
70176
Country
Germany
Facility Name
GSK Investigational Site
City
Tuebingen
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
GSK Investigational Site
City
Ulm
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
89075
Country
Germany
Facility Name
GSK Investigational Site
City
Alzenau
State/Province
Bayern
ZIP/Postal Code
63755
Country
Germany
Facility Name
GSK Investigational Site
City
Guenzburg
State/Province
Bayern
ZIP/Postal Code
89312
Country
Germany
Facility Name
GSK Investigational Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
GSK Investigational Site
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93053
Country
Germany
Facility Name
GSK Investigational Site
City
Unterhaching
State/Province
Bayern
ZIP/Postal Code
82008
Country
Germany
Facility Name
GSK Investigational Site
City
Bad Homburg
State/Province
Hessen
ZIP/Postal Code
61348
Country
Germany
Facility Name
GSK Investigational Site
City
Schwerin
State/Province
Mecklenburg-Vorpommern
ZIP/Postal Code
19053
Country
Germany
Facility Name
GSK Investigational Site
City
Schwerin
State/Province
Mecklenburg-Vorpommern
ZIP/Postal Code
19055
Country
Germany
Facility Name
GSK Investigational Site
City
Achim
State/Province
Niedersachsen
ZIP/Postal Code
28832
Country
Germany
Facility Name
GSK Investigational Site
City
Aachen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
52062
Country
Germany
Facility Name
GSK Investigational Site
City
Bad Honnef
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53604
Country
Germany
Facility Name
GSK Investigational Site
City
Bochum
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
44869
Country
Germany
Facility Name
GSK Investigational Site
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01097
Country
Germany
Facility Name
GSK Investigational Site
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01309
Country
Germany
Facility Name
GSK Investigational Site
City
Jena
State/Province
Thueringen
ZIP/Postal Code
07743
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
10961
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
12163
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
13439
Country
Germany
Facility Name
GSK Investigational Site
City
Chieti Scalo
State/Province
Abruzzo
ZIP/Postal Code
66013
Country
Italy
Facility Name
GSK Investigational Site
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
GSK Investigational Site
City
San Felice A Cancello - Caserta
State/Province
Campania
ZIP/Postal Code
81027
Country
Italy
Facility Name
GSK Investigational Site
City
Cassino (FR)
State/Province
Lazio
ZIP/Postal Code
03043
Country
Italy
Facility Name
GSK Investigational Site
City
Roma
State/Province
Lazio
ZIP/Postal Code
00148
Country
Italy
Facility Name
GSK Investigational Site
City
Roma
State/Province
Lazio
ZIP/Postal Code
00163
Country
Italy
Facility Name
GSK Investigational Site
City
Brescia
State/Province
Lombardia
ZIP/Postal Code
25125
Country
Italy
Facility Name
GSK Investigational Site
City
Castellanza (VA)
State/Province
Lombardia
ZIP/Postal Code
21053
Country
Italy
Facility Name
GSK Investigational Site
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Facility Name
GSK Investigational Site
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
GSK Investigational Site
City
Rho
State/Province
Lombardia
ZIP/Postal Code
20017
Country
Italy
Facility Name
GSK Investigational Site
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
Facility Name
GSK Investigational Site
City
Lido Di Camaiore (LU)
State/Province
Toscana
ZIP/Postal Code
55043
Country
Italy
Facility Name
GSK Investigational Site
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56126
Country
Italy
Facility Name
GSK Investigational Site
City
Perugia
State/Province
Umbria
ZIP/Postal Code
06156
Country
Italy
Facility Name
GSK Investigational Site
City
Valdagno (VI)
State/Province
Veneto
ZIP/Postal Code
36078
Country
Italy
Facility Name
GSK Investigational Site
City
Verona
State/Province
Veneto
ZIP/Postal Code
37126
Country
Italy
Facility Name
GSK Investigational Site
City
Baracaldo/Vizcaya
ZIP/Postal Code
48903
Country
Spain
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08014
Country
Spain
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
GSK Investigational Site
City
Burgos
ZIP/Postal Code
09006
Country
Spain
Facility Name
GSK Investigational Site
City
Castellón
ZIP/Postal Code
12004
Country
Spain
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28006
Country
Spain
Facility Name
GSK Investigational Site
City
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
GSK Investigational Site
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
Facility Name
GSK Investigational Site
City
San Sebastián
ZIP/Postal Code
20014
Country
Spain
Facility Name
GSK Investigational Site
City
San Vicente Del Raspeig/Alicante
ZIP/Postal Code
03690
Country
Spain
Facility Name
GSK Investigational Site
City
Valencia
ZIP/Postal Code
46010
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
29854923
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.
Results Reference
derived

Learn more about this trial

A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease

We'll reach out to this number within 24 hrs