Phase 2
Completed N=574
Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's Disease
Source: ClinicalTrials.gov NCT00708552 ↗Enrolled (actual)
574
Serious AEs
4.7%
Results posted
Feb 2018
Primary outcomePrimary: Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24 — -0.3; 0.8; 0.4; -0.5 Score on scale — p=0.159
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.
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 |
-0.3; 0.8; 0.4; -0.5 | 0.159 |
| PRIMARY Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score at Week 24 |
4.0; 4.2; 3.9; 3.7 | 0.254 |
| SECONDARY Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24 |
-2.3; -4.0; -4.4; -0.3 | 0.423 |
| SECONDARY 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 |
-1.3; 0.1; -0.4; -1.0; -1.3; -2.4 | 0.096 |
| SECONDARY 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 |
0.0; 1.6; 1.3; -0.1; -3.7; -5.8 | 0.138 |
| SECONDARY Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 24 |
3.8; 4.0; 3.7; 3.5 | 0.146 |
| SECONDARY Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 24 |
4.2; 4.4; 4.1; 3.9 | 0.295 |
| SECONDARY Change From Baseline in ADAS-Cog Total Score at Week 12 |
-0.1; 0.0; -0.2; -0.6 | 0.847 |
| SECONDARY CIBIC+ Score at Week 12 |
3.9; 4.0; 3.9; 3.7 | 0.320 |
| SECONDARY Change From Baseline in RBANS Total Score at Week 12 |
-6.7; -8.7; -5.9; -3.4 | 0.257 |
| SECONDARY 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 |
-0.6; -0.4; -0.5; -0.5; -7.5; -8.3 | 0.798 |
| SECONDARY 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 |
0.4; 0.4; 0.2; -0.9; -6.4; -10.0 | 0.908 |
| SECONDARY Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 12 |
3.8; 3.8; 3.7; 3.6 | 0.671 |
| SECONDARY Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 12 |
4.0; 4.1; 4.1; 3.7 | 0.369 |
| SECONDARY Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score at Weeks 12 and 24 |
-0.4; -1.1; -0.1; 0.2; -1.0; -1.4 | 0.417 |
| SECONDARY Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) Total Score at Week 24 |
0.0; -0.1; 0.3; 0.3 | 0.594 |
| SECONDARY Change From Baseline in MMSE Total Score at Week 24 |
-0.3; -0.3; -0.1; 0.5 | 0.966 |
| SECONDARY Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24 |
-0.6; -0.5; -0.4; -0.2; -0.7; -0.7 | 0.869 |
| SECONDARY Number of Participants With Any Adverse Event (Serious and Non-serious) and Serious Adverse Events (SAEs) |
45; 42; 39; 65; 7; 7 | — |
| SECONDARY Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) |
1; 2; 2; 0; 0; 3 | — |
| SECONDARY Number of Participants With Hematology Data of PCC ATOT |
1; 0; 0; 1; 2; 1 | — |
| SECONDARY Number of Participants With Chemistry Data of PCC ATOT |
2; 0; 0; 1; 1; 0 | — |
| SECONDARY 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 |
-0.3; 0.0; -0.1; 1.6; -3.4; -0.1 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein at Week 24 |
-0.5; -0.5; -0.6; -0.8; -0.8; -0.9 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameter Blood Urea Nitrogen /Creatinine Ratio at Week 24 |
0.8; 2.3; -3.7; -0.3 | — |
| SECONDARY 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 |
-0.008; -0.012; -0.025; -0.013; 0.5; 0.3 | — |
| SECONDARY Change From Baseline in Clinical Chemistry Parameters Creatinine, Direct Bilirubin and Total Bilirubin at Week 24 |
-0.3; 1.2; 5.7; 1.4; -0.1; 0.1 | — |
| SECONDARY Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 |
0.001; 0.002; 0.003; -0.001; -0.011; -0.006 | — |
| SECONDARY Change From Baseline in Hematology Parameter Hematocrit |
0.0038; 0.0037; -0.0003; 0.0002 | — |
| SECONDARY Change From Baseline in Hematology Parameters Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Week 24 |
-1.1; -1.6; -1.8; -1.6; -5.3; -5.9 | — |
| SECONDARY Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin at Week 24 |
-0.21; -0.19; -0.10; -0.08 | — |
| SECONDARY Change From Baseline in Hematology Parameter Mean Corpuscle Volume and Mean Platelet Volume at Week 24 |
0.8; 1.4; 0.6; 0.9; -0.01; -0.04 | — |
| SECONDARY Change From Baseline in Hematology Parameter Red Blood Cell Count at Week 24 |
-0.03; 0.01; -0.08; -0.07 | — |
| SECONDARY Number of Participants With Electrocardiogram (ECG) Findings as Assessed by Investigator and Central Cardiologist |
58; 60; 59; 67; 0; 1 | — |
| SECONDARY Exposure Estimates for SB-742457 Area Under Curve Over the Dosing Interval at Steady State (AUCτss) |
1434.89; 3424.91 | — |
| SECONDARY Exposure Estimates for SB-742457 Minimum Concentration at Steady State (Cmin-ss) |
46.03; 37.47 | — |
| SECONDARY Exposure Estimates for Donepezil Average Concentration at Steady State (Cavgss) |
17.53; 31.80 | — |
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.
Data sourced from ClinicalTrials.gov (NCT00708552). 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.