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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DONEPEZIL + SB-742457 15 MG | Experimental | SB-742457 - 15mg added to existing donepezil treatment |
|
| DONEPEZIL + PLACEBO | Placebo Comparator | Placebo added to existing donepezil |
|
| DONEPEZIL + SB-742457 35 MG | Experimental | SB-742457 - 35mg added to existing donepezil |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SB-742457 15mg | Drug | SB-742457 - 15mg added to existing donepezil treatment |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline(Week 0) and Week 24 |
| 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. | Baseline(Week 0) and Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Litchfield Park | Arizona | 85340 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29854923 | Derived | 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. |
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Out of 1132 participants screened, 725 entered into 4-week placebo run-in period out of which 41 participants were placebo run-in failures. Out of 684 participants randomized, 682 were included in safety population (1 participant each from Donepezil+Placebo and Donepezil+SB742457 35 milligram [mg] group failed to take a dose of study medication).
A total of 684 participants were randomized from 100 centers i.e. Australia, Argentina, Chile, Canada, United States of America, Czech Republic, Spain, Italy, Germany between 01 July 2008 and 16 November 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | Donepezil + Placebo | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| SB-742457 35mg |
| Drug |
SB-742457 - 35mg added to existing donepezil |
|
| Placebo | Drug | Placebo added to existing donepezil |
|
| donepezil 5-10mg | Drug | existing donepezil treatment |
|
| Baseline (Week 0) and Week 24 |
| 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 | Baseline (Week 0) and Week 12, 36 and 48 |
| 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. | Baseline (Week 0) and Week 12, 36, 48 |
| 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. | Baseline (Week 0) and Week 12, 36 and 48 |
| 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. | Baseline (Week 0) and Week 12, 24, 36 and 48 |
| 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. | Baseline (Week 0) and Week 24 and 48 |
| 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. | Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal) |
| 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). | Up to Week 48 |
| 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). | Up to Week 48 |
| 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. | Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 |
| 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. | Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 |
| 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. | Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 |
| 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. | Baseline (Week 0) to Week 24 and Week 48 |
| 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. | Baseline (Week 0) to Week 24 and Week 48 |
| 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. | Baseline (Week 0) to Week 24 and Week 48 |
| Fresno |
| California |
| 93720 |
| United States |
| GSK Investigational Site | Rancho Mirage | California | 92270 | United States |
| GSK Investigational Site | San Francisco | California | 94109 | United States |
| GSK Investigational Site | Hallandale | Florida | 33009 | United States |
| GSK Investigational Site | Hialeah | Florida | 33016 | United States |
| GSK Investigational Site | Paterson | New Jersey | 08759 | United States |
| GSK Investigational Site | Syracuse | New York | 13210 | United States |
| GSK Investigational Site | Winston-Salem | North Carolina | 27103 | United States |
| GSK Investigational Site | Columbus | Ohio | 43210 | United States |
| GSK Investigational Site | Tulsa | Oklahoma | 74104 | United States |
| GSK Investigational Site | Memphis | Tennessee | 38119 | United States |
| GSK Investigational Site | Austin | Texas | 78757 | United States |
| GSK Investigational Site | Bennington | Vermont | 05201 | United States |
| GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | C1022AAO | Argentina |
| GSK Investigational Site | Ciudad Autonoma de Buenos Aires | Buenos Aires | C1405BCH | Argentina |
| GSK Investigational Site | Ciudad de Buenos Aires | Buenos Aires | C1431FWO | Argentina |
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| GSK Investigational Site | Córdoba | Córdoba Province | 5000 | Argentina |
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| GSK Investigational Site | Santa Fe | 3000 | Argentina |
| GSK Investigational Site | Kogarah | New South Wales | 2217 | Australia |
| GSK Investigational Site | Herston | Queensland | 4029 | Australia |
| GSK Investigational Site | Woodville | South Australia | 5011 | Australia |
| GSK Investigational Site | Ballarat | Victoria | 3350 | Australia |
| GSK Investigational Site | Heidelberg West | Victoria | 3084 | Australia |
| GSK Investigational Site | Kew | Victoria | 3101 | Australia |
| GSK Investigational Site | Nedlands | Western Australia | 6009 | Australia |
| GSK Investigational Site | Saint John | New Brunswick | E2L 3L6 | Canada |
| GSK Investigational Site | Kentville | Nova Scotia | B4N 4K9 | Canada |
| GSK Investigational Site | Ottawa | Ontario | K1G 4G3 | Canada |
| GSK Investigational Site | Peterborough | Ontario | K9H 2P4 | Canada |
| GSK Investigational Site | Toronto | Ontario | M3B 2S7 | Canada |
| GSK Investigational Site | Toronto | Ontario | M6M 3Z5 | Canada |
| GSK Investigational Site | Greenfield Park | Quebec | J4V 2J2 | Canada |
| GSK Investigational Site | Montreal | Quebec | H1T 2M4 | Canada |
| GSK Investigational Site | Sherbrooke | Quebec | J1H 1Z1 | Canada |
| GSK Investigational Site | Sherbrooke | Quebec | J1J 3H5 | Canada |
| GSK Investigational Site | Québec | G1R 3X5 | Canada |
| GSK Investigational Site | Santiago | Región Metro de Santiago | 7510186 | Chile |
| GSK Investigational Site | Santiago | Región Metro de Santiago | 7560356 | Chile |
| GSK Investigational Site | Viña del Mar | Valparaiso | 252-0997 | Chile |
| GSK Investigational Site | Santiago | Chile |
| GSK Investigational Site | Mělník | 27601 | Czechia |
| GSK Investigational Site | Olomouc | 775 20 | Czechia |
| GSK Investigational Site | Ostrava | 702 00 | Czechia |
| GSK Investigational Site | Pardubice | 53203 | Czechia |
| GSK Investigational Site | Pilsen | 301 00 | Czechia |
| GSK Investigational Site | Prague | 10000 | Czechia |
| GSK Investigational Site | Prague | 110 00 | Czechia |
| GSK Investigational Site | Prague | 14059 | Czechia |
| GSK Investigational Site | Ellwangen | Baden-Wurttemberg | 73479 | Germany |
| GSK Investigational Site | Stuttgart | Baden-Wurttemberg | 70176 | Germany |
| GSK Investigational Site | Tübingen | Baden-Wurttemberg | 72076 | Germany |
| GSK Investigational Site | Ulm | Baden-Wurttemberg | 89075 | Germany |
| GSK Investigational Site | Alzenau in Unterfranken | Bavaria | 63755 | Germany |
| GSK Investigational Site | Günzburg | Bavaria | 89312 | Germany |
| GSK Investigational Site | Munich | Bavaria | 81675 | Germany |
| GSK Investigational Site | Regensburg | Bavaria | 93053 | Germany |
| GSK Investigational Site | Unterhaching | Bavaria | 82008 | Germany |
| GSK Investigational Site | Bad Homburg | Hesse | 61348 | Germany |
| GSK Investigational Site | Achim | Lower Saxony | 28832 | Germany |
| GSK Investigational Site | Schwerin | Mecklenburg-Vorpommern | 19053 | Germany |
| GSK Investigational Site | Schwerin | Mecklenburg-Vorpommern | 19055 | Germany |
| GSK Investigational Site | Aachen | North Rhine-Westphalia | 52062 | Germany |
| GSK Investigational Site | Bad Honnef | North Rhine-Westphalia | 53604 | Germany |
| GSK Investigational Site | Bochum | North Rhine-Westphalia | 44869 | Germany |
| GSK Investigational Site | Dresden | Saxony | 01097 | Germany |
| GSK Investigational Site | Dresden | Saxony | 01309 | Germany |
| GSK Investigational Site | Jena | Thuringia | 07743 | Germany |
| GSK Investigational Site | Berlin | 10961 | Germany |
| GSK Investigational Site | Berlin | 12163 | Germany |
| GSK Investigational Site | Berlin | 13439 | Germany |
| GSK Investigational Site | Chieti Scalo | Abruzzo | 66013 | Italy |
| GSK Investigational Site | Naples | Campania | 80131 | Italy |
| GSK Investigational Site | San Felice A Cancello - Caserta | Campania | 81027 | Italy |
| GSK Investigational Site | Cassino (FR) | Lazio | 03043 | Italy |
| GSK Investigational Site | Rome | Lazio | 00148 | Italy |
| GSK Investigational Site | Rome | Lazio | 00163 | Italy |
| GSK Investigational Site | Brescia | Lombardy | 25125 | Italy |
| GSK Investigational Site | Castellanza (VA) | Lombardy | 21053 | Italy |
| GSK Investigational Site | Milan | Lombardy | 20122 | Italy |
| GSK Investigational Site | Milan | Lombardy | 20132 | Italy |
| GSK Investigational Site | Rho | Lombardy | 20017 | Italy |
| GSK Investigational Site | Turin | Piedmont | 10126 | Italy |
| GSK Investigational Site | Lido Di Camaiore (LU) | Tuscany | 55043 | Italy |
| GSK Investigational Site | Pisa | Tuscany | 56126 | Italy |
| GSK Investigational Site | Perugia | Umbria | 06156 | Italy |
| GSK Investigational Site | Valdagno (VI) | Veneto | 36078 | Italy |
| GSK Investigational Site | Verona | Veneto | 37126 | Italy |
| GSK Investigational Site | Baracaldo/Vizcaya | 48903 | Spain |
| GSK Investigational Site | Barcelona | 08003 | Spain |
| GSK Investigational Site | Barcelona | 08014 | Spain |
| GSK Investigational Site | Barcelona | 08907 | Spain |
| GSK Investigational Site | Burgos | 09006 | Spain |
| GSK Investigational Site | Castellon | 12004 | Spain |
| GSK Investigational Site | Madrid | 28006 | Spain |
| GSK Investigational Site | Murcia | 30120 | Spain |
| GSK Investigational Site | Salamanca | 37007 | Spain |
| GSK Investigational Site | San Sebastián | 20014 | Spain |
| GSK Investigational Site | San Vicente Del Raspeig/Alicante | 03690 | Spain |
| GSK Investigational Site | Valencia | 46010 | Spain |
| FG001 | Donepezil + SB-742457 15 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| FG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Out of 682 participants, 5 participants did not have at least one post-Baseline or health outcomes assessment. Hence a total of 677 participants were included in intent-to-treat (ITT) population and they were used to assess Baseline characteristics.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Donepezil + Placebo | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| BG001 | Donepezil + SB-742457 15 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| BG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | ITT population. Only those participants with data available at the indicated time points were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline(Week 0) and Week 24 |
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| Primary | 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. | ITT population. Only those participants with data available at the indicated time points were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline(Week 0) and Week 24 |
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| Secondary | 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. | ITT population. Only those participants with data available at the indicated time points were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline (Week 0) and Week 24 |
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| Secondary | 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 | ITT population. Only those participants with data available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline (Week 0) and Week 12, 36 and 48 |
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| Secondary | 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. | ITT population. Only those participants with data available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline (Week 0) and Week 12, 36, 48 |
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| Secondary | 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. | ITT population. Only those participants with data available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline (Week 0) and Week 12, 36 and 48 |
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| 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 | 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. | ITT population. Only those participants with data available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline (Week 0) and Week 12, 24, 36 and 48 |
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| Secondary | 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. | ITT population. Only those participants with data available at the specified time points were analyzed. | Posted | Least Squares Mean | Standard Error | Score on scale | Baseline (Week 0) and Week 24 and 48 |
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| Secondary | 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. | Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. | Posted | Count of Participants | Participants | Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal) |
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| Secondary | 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). | Safety population. Only those participants with data available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Up to Week 48 |
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| Secondary | 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). | Safety population. Only those participants with data available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Up to Week 48 |
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| Secondary | 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. | PK population included all participants for whom a pharmacokinetic sample was obtained and analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram hour per milliliter (ng*h/mL) | Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 |
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| Secondary | 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. | PK population. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 |
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| Secondary | 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. | Donepezil PK population comprised of participants who received a stable dose of donepezil 5 mg/7.5 mg/10 mg/15 mg. Analysis is exclusively for Cavgss of donepezil therefore the two arms SB-742457 15 mg and SB-742457 35 mg have not been presented. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48 |
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| Secondary | 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. | PGx ITT Population consisted of all participants in the ITT population who had evaluable PGx data. Only those participants with APOE gene and available at the specified time point were analyzed. | Posted | Mean | Standard Deviation | Score on scale | Baseline (Week 0) to Week 24 and Week 48 |
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| Secondary | 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. | PGx ITT Population. Only those participants with APOE gene and available at the specified time point were analyzed. | Posted | Mean | Standard Deviation | Score on scale | Baseline (Week 0) to Week 24 and Week 48 |
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| Secondary | 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. | PGx ITT Population. Only those participants with APOE gene and available at the specified time point were analyzed. | Posted | Mean | Standard Deviation | Score on scale | Baseline (Week 0) to Week 24 and Week 48 |
|
AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal).
Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Donepezil + Placebo | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. | 1 | 225 | 17 | 225 | 41 | 225 |
| EG001 | Donepezil + SB-742457 15 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. | 5 | 221 | 26 | 221 | 32 | 221 |
| EG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. | 4 | 236 | 27 | 236 | 33 | 236 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cerebrovascular accident | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Dementia Alzheimer's type | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Loss of consciousness | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Psychomotor hyperactivity | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Abdominal abscess | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Bronchopneumonia | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Skull fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Splenic injury | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Adams-Stokes syndrome | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Arteriosclerosis coronary artery | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Sick sinus syndrome | Cardiac disorders | MedDRA | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Colonic polyp | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Diverticulum | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Oesophageal obstruction | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| |
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Glioblastoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Oesophageal carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Penile neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
| |
| Death | General disorders | MedDRA | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
| |
| Circulatory collapse | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Disorientation | Psychiatric disorders | MedDRA | Systematic Assessment |
| |
| Biliary colic | Hepatobiliary disorders | MedDRA | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
| |
| Urethral stenosis | Renal and urinary disorders | MedDRA | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| C548140 | 3-benzenesulfonyl-8-piperazin-1-ylquinoline |
| D000077265 | Donepezil |
| ID | Term |
|---|---|
| D007189 | Indans |
| D007192 | Indenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011083 | Polycyclic Compounds |
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
SB-742457 35mg versus placebo at Week 24 |
| MMRM |
The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country. |
| 0.012 |
| Mean Difference (Net) |
| -1.5 |
| 2-Sided |
| 95 |
| -2.7 |
| -0.3 |
| Superiority or Other |
Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
|
|
|
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
|
|
|
| OG001 | Donepezil + SB-742457 15 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
|
|
|
Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
|
|
|
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
|
|
|
| OG001 | Donepezil + SB-742457 15 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
|
|
|
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
|
|
|
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
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| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
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Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
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| Units | Counts |
|---|---|
| Participants |
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| OG002 | Donepezil 10 mg | Participants received a stable dose of donepezil 10 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. |
| OG003 | Donepezil 15 mg | Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. |
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| OG001 | Donepezil + SB-742457 15 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
|
|
Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
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| OG002 | Donepezil + SB-742457 35 mg | Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks. |
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