Phase 2
Completed N=682
A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease
Source: ClinicalTrials.gov NCT00710684 ↗Enrolled (actual)
682
Serious AEs
10.3%
Results posted
Dec 2017
Primary outcomePrimary: Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24 — 1.2; 0.5; -0.4 Score on scale — p=0.279
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24 |
1.2; 0.5; -0.4 | 0.279 |
| PRIMARY Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24 |
0.9; 0.8; 0.7 | 0.711 |
| SECONDARY Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24 |
-3.6; -5.9; -4.0 | 0.174 |
| SECONDARY Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48 |
0.4; 0.1; -0.9; 2.1; 2.1; 0.9 | 0.631 |
| SECONDARY Change From Baseline in CDR-SB Score at Week 12, 36 and 48 |
0.5; 0.4; 0.2; 1.2; 1.4; 1.0 | 0.387 |
| SECONDARY Change From Baseline in RBANS Score at Week 12, 36 and 48 |
-7.2; -8.5; -6.5; -3.9; -4.8; -1.8 | 0.337 |
| SECONDARY 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 |
-1.4; -0.8; 0.3; -3.4; -1.9; -1.4 | 0.396 |
| SECONDARY Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48 |
-0.4; -0.3; 0.1; -1.1; -1.3; -0.7 | 0.962 |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase |
125; 137; 146; 17; 26; 27 | — |
| SECONDARY Number of Participants With Parameters of Clinical Concern - Hematology |
1; 0; 4; 2; 2; 1 | — |
| SECONDARY Number of Participants With Parameters of Clinical Concern - Clinical Chemistry |
2; 4; 4; 5; 6; 4 | — |
| SECONDARY Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss) |
1640.76; 4160.29 | — |
| SECONDARY Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss) |
53.42; 135.05 | — |
| SECONDARY Exposure Estimates for Donepezil (Cavgss) |
20.72; 17.68; 39.79; 36.60 | — |
| SECONDARY Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene |
1.9; 1.0; -0.1; 4.7; 4.2; 1.8 | — |
| SECONDARY Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene |
1.1; 0.6; 0.8; 1.8; 1.5; 1.4 | — |
| SECONDARY Change From Baseline in RBANS Scale in Participants With APOE4 Gene |
-5.2; -6.0; -6.0; -7.7; -11.3; -5.9 | — |
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.
Data sourced from ClinicalTrials.gov (NCT00710684). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.