# Presentation: 175667

## Alzheimer Disease Assessment Scale—Cognitive Subscale (ADAS-cog) 11-Item

|  | Score range |
| --- | --- |
| Memory and new learning | 0 - 35 |
| 	Word recall	(mean number of words not recalled) | 0 - 10 |
| 	Orientation	(one point for each incorrect response) | 0 - 8 |
| 	Word recognition	(mean number of incorrect responses) | 0 - 12 |
| 	Remembering test instructions | 0 - 5 |
| Language | 0 - 25 |
| 	Commands | 0 - 5 |
| 	Spoken language ability | 0 - 5 |
| 	Naming objects/fingers | 0 - 5 |
| 	Word-finding difficulty | 0 - 5 |
| 	Comprehension | 0 - 5 |
| Praxis | 0 - 10 |
| 	Constructional praxis | 0 - 5 |
| 	Ideational praxis | 0 - 5 |
| Total  | 0 - 70 |

**Increasing scores indicate worsening cognitive function.****Rosen WG, et al. *****Am J Psychiatry*****. 1984;141:1356-1364.**

## Treatment Difference at Wk 24 on ADAS-cog by CountryCore Study—ITT+RDO Population

**Austria (N = 9)**

**Belgium (N = 21)**

**Canada (N = 41)**

**Germany (N = 63)**

**Spain (N = 59)**

**France (N = 63)**

**Great Britain (N = 48)**

**Italy (N = 118)**

**Netherlands (N = 18)**

**Norway (N = 7)**

**Portugal (N = 9)**

**Turkey (N = 45)**

**–****10**

**0**

**10**

**20**

**LS mean difference (95% CI).**

**–****20**

**–****39.67 **

**–****29.92 **

**46.92**

**Favor Exelon**

**Favor placebo**

## Duration of Nausea and Vomiting and Number of Events per PatientCore Study

|  | Nausea
n (%) | Vomitingn (%) |
| --- | --- | --- |
| Duration | Events, N = 137 | Events, N = 77 |
| 1 - 7 days | 55 (40.1) | 47 (61.0) |
| 8 - 14 days | 16 (11.7) | 7 (9.1) |
| 15 - 21 days | 13 (9.5) | 8 (10.4) |
| 22 - 28 days | 11 (8.0) | 5 (6.5) |
| > 28 days | 22 (16.1) | 4 (5.2) |
| Continuing† | 20 (14.6) | 6 (7.8) |
| Number of events/patient | Patients, N = 105 | Patients, N = 60 |
| 1 | 81 (77.1) | 49 (81.7) |
| 2 | 19 (18.1) | 8 (13.3) |
| 3 | 2 (1.9) | 1 (1.7) |
| > 3 | 3 (2.9) | 2 (3.3) |

**† ****Events with no end dates recorded, which may or may not have resolved****by last study visit.**

## Duration of Tremor and Number of These Events per PatientCore Study

|  | Tremor
n (%) |
| --- | --- |
| Duration | Total events = 40 |
| 1 - 7 days | 11 (27.5) |
| 8 - 14 days |   3 (7.5) |
| 15 - 21 days |   1 (2.5) |
| 22 - 28 days |   3 (7.5) |
| > 28 days |   4 (10.0) |
| Continuing† | 18 (45.0) |
| Number of events/patient | Total patients = 37 |
|    1 | 34 |
|    2 | 3 |
|    3 | 0 |
| > 3 | 0 |

**1 episode: 34 patients; 2 episodes: 3 patients.**
**† ****Events with no end dates recorded, which may or may not have resolved by last study visit.**

## AE of Tremor Over TimeCore and Extension Studies

|  |  | Core |  |  |  |  | Extension |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  | Exelon  n/N (%) |  | Placebo  n/N (%) |  |  | Exe-Exelon n/N (%) |  | Plc-Exelon n/N (%) |
| Titration period, wk |  |  |  |  | Titration period, wk |  |  |  |
|    0 - 4  | 7/362 (1.9) |  | 3/179 (1.7) |  |   24 - 28 | 0 |  | 1/123 (0.8) |
| > 4 - 8  | 9/343 (2.6) |  | 0 |  | > 28 - 32 | 3/207 (1.4) |  | 6/119 (5.0) |
| > 8 - 12  | 15/324 (4.6) |  | 1/165 (0.6) |  | > 32 - 36 | 2/202 (1.0) |  | 6/115 (5.2) |
| > 12 - 16  | 6/301 (2.0) |  | 2/162 (1.2) |  | > 36 - 40 | 2/195 (1.0) |  | 2/107 (1.9) |
| Maintenanceperiod, wk |  |  |  |  | Maintenanceperiod, wk |  |  |  |
| > 16 - 20  | 2/281 (0.7) |  |  | 1/158 (0.6) | > 40 - 48 | 1/191 (0.5) |  | 1/102 (1.0) |
| > 20 - 24  | 1/271 (0.4) |  |  | 0 |  |  |  |  |

**Patients are counted more than once if event continues through multiple periods. **

## Change on ADAS-cog Sub-items at Wk 24Core Study—OC Population

|  | Mean ± SD |  |  |  |  |
| --- | --- | --- | --- | --- | --- |
|  | Exelon (N = 290) |  | Placebo (N = 159) |  |  |
| ADAS-cog sub-item | N | Change atWk 24 | N | Change atWk 24 | p value† |
| Item 1: word recall | 255 | 0.5 ± 1.3 | 139 |   0.1 ± 1.3 |  0.014* |
| Item 2: commands | 258 | 0.3 ± 1.2 | 141 |   0.0 ± 1.3 |  0.023* |
| Item 3: constructional praxis | 249 | 0.2 ± 1.0 | 135 | –0.1 ± 1.1 | 0.095 |
| Item 4: naming objects/fingers | 258 | 0.1 ± 0.8 | 142 | –0.1 ± 0.9 |  0.037* |
| Item 5: ideational praxis | 245 | 0.4 ± 1.5 | 134 | –0.1 ± 1.3 | < 0.001* |
| Item 6: orientation | 259 | 0.4 ± 1.8 | 143 | –0.1 ± 1.7 | 0.060 |
| Item 7: word recognition | 249 | 0.5 ± 3.3 | 137 | –0.2 ± 3.6 | 0.106 |
| Item 8: remembering test instructions | 256 | 0.2 ± 1.3 | 141 | –0.1 ± 1.2 |  0.013* |
| Item 9: spoken language ability | 259 | 0.1 ± 1.2 | 142 | –0.3 ± 1.0 |  0.032* |
| Item 10: word finding difficulty | 258 | 0.1 ± 1.0 | 142 |   0.0 ± 1.0 | 0.421 |
| Item 11: comprehension | 259 | 0.2 ± 1.0 | 142 | –0.2 ± 1.0 |  0.012* |

********p***** < 0.05**
**† *****p***** value based on van Elteren test blocking for country.**

## Major Protocol ViolationsCore Study

|  | Exelon  | Placebo  | Total  |
| --- | --- | --- | --- |
| Protocol violation | N = 362n (%) | N = 179n (%)  | N = 541n (%)  |
| ≥ 1 protocol violation  | 82 (22.7)  | 33 (18.4)  | 115 (21.3)  |
| MMSE score < 10 or > 24  | 6 (1.7)  | 3 (1.7)  | 9 (1.7)  |
| Date diagnosis PD > date of first symptoms of PDD –2 yr  | 14 (3.9)  | 3 (1.7)  | 17 (3.1)  |
| Increased dose or newly introduced psychotropic/ dopaminergic medication  | 39 (10.8)  | 18 (10.1)  | 57 (10.5) |

## Dopaminergic Agents—Dose Increase After Start of Study DrugCore Study

|  | ExelonN = 362n (%) | PlaceboN = 179n (%) |
| --- | --- | --- |
| Dopa and dopa derivatives  | 20 (5.5)  | 8 (4.5)  |
| Dopamine agonists  |   3 (0.8)  | 1 (0.6)  |
| Other dopaminergic agents  |   2 (0.6)  | 0  |

**Doses were required to remain unchanged unless clinically indicated.**