Trial Outcomes & Findings for Idalopirdine in Patients With Mild-moderate Alzheimer's Disease Treated With Donepezil (NCT NCT02006641)
NCT ID: NCT02006641
Last Updated: 2018-02-20
Results Overview
Change from baseline to Week 24 in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score. The Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-cog) is a 11-item neuropsychological test that assess the severity of cognitive impairment. The items determine the patient's orientation, memory, language, and praxis. Total score of the 11 items range from 0 to 70 (lower score indicates lower cognitive impairment).
COMPLETED
PHASE3
858 participants
Baseline and Week 24
2018-02-20
Participant Flow
Participant milestones
| Measure |
Placebo
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Overall Study
STARTED
|
284
|
290
|
284
|
|
Overall Study
Treated
|
282
|
285
|
281
|
|
Overall Study
COMPLETED
|
258
|
257
|
248
|
|
Overall Study
NOT COMPLETED
|
26
|
33
|
36
|
Reasons for withdrawal
| Measure |
Placebo
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Overall Study
Withdrawal before treatment
|
2
|
5
|
3
|
|
Overall Study
Adverse Event
|
15
|
11
|
15
|
|
Overall Study
Protocol Violation
|
0
|
2
|
2
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
7
|
12
|
11
|
|
Overall Study
Other reason: patient didn't show up
|
1
|
0
|
0
|
|
Overall Study
Other reason:patient didn't want to come
|
0
|
0
|
1
|
|
Overall Study
Other reason: patient has moved
|
1
|
0
|
1
|
|
Overall Study
Other reason: caregiver in hospital
|
0
|
1
|
0
|
|
Overall Study
Other reason: patient's wife has died
|
0
|
0
|
1
|
|
Overall Study
Other reason: hospitalisation
|
0
|
1
|
0
|
|
Overall Study
Other reason: caregiver impossibility
|
0
|
0
|
1
|
|
Overall Study
Other reason: protocol non-compliance
|
0
|
0
|
1
|
Baseline Characteristics
Idalopirdine in Patients With Mild-moderate Alzheimer's Disease Treated With Donepezil
Baseline characteristics by cohort
| Measure |
Placebo
n=282 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=285 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=281 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Total
n=848 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
42 Participants
n=99 Participants
|
47 Participants
n=107 Participants
|
41 Participants
n=206 Participants
|
130 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
230 Participants
n=99 Participants
|
227 Participants
n=107 Participants
|
230 Participants
n=206 Participants
|
687 Participants
n=7 Participants
|
|
Age, Continuous
|
73.4 years
STANDARD_DEVIATION 8.3 • n=99 Participants
|
74.9 years
STANDARD_DEVIATION 8.1 • n=107 Participants
|
75.0 years
STANDARD_DEVIATION 8.0 • n=206 Participants
|
74.4 years
STANDARD_DEVIATION 8.1 • n=7 Participants
|
|
Sex: Female, Male
Female
|
181 Participants
n=99 Participants
|
172 Participants
n=107 Participants
|
169 Participants
n=206 Participants
|
522 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
101 Participants
n=99 Participants
|
113 Participants
n=107 Participants
|
112 Participants
n=206 Participants
|
326 Participants
n=7 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
10 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
31 Participants
n=7 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
NA Participants
n=99 Participants
|
NA Participants
n=107 Participants
|
NA Participants
n=206 Participants
|
NA Participants
n=7 Participants
|
|
Race (NIH/OMB)
Asian
|
20 Participants
n=99 Participants
|
24 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
68 Participants
n=7 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
NA Participants
n=99 Participants
|
NA Participants
n=107 Participants
|
NA Participants
n=206 Participants
|
NA Participants
n=7 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
16 Participants
n=7 Participants
|
|
Race (NIH/OMB)
White
|
250 Participants
n=99 Participants
|
249 Participants
n=107 Participants
|
244 Participants
n=206 Participants
|
743 Participants
n=7 Participants
|
|
Race (NIH/OMB)
More than one race
|
NA Participants
n=99 Participants
|
NA Participants
n=107 Participants
|
NA Participants
n=206 Participants
|
NA Participants
n=7 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
21 Participants
n=7 Participants
|
|
Region of Enrollment
Argentina
|
23 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
73 Participants
n=7 Participants
|
|
Region of Enrollment
Hungary
|
7 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
|
Region of Enrollment
Czechia
|
16 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
17 Participants
n=206 Participants
|
48 Participants
n=7 Participants
|
|
Region of Enrollment
United States
|
54 Participants
n=99 Participants
|
58 Participants
n=107 Participants
|
52 Participants
n=206 Participants
|
164 Participants
n=7 Participants
|
|
Region of Enrollment
United Kingdom
|
29 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
82 Participants
n=7 Participants
|
|
Region of Enrollment
Portugal
|
4 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
15 Participants
n=7 Participants
|
|
Region of Enrollment
Canada
|
11 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
10 Participants
n=206 Participants
|
30 Participants
n=7 Participants
|
|
Region of Enrollment
South Korea
|
14 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
46 Participants
n=7 Participants
|
|
Region of Enrollment
Finland
|
4 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
13 Participants
n=7 Participants
|
|
Region of Enrollment
Taiwan
|
6 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
17 Participants
n=7 Participants
|
|
Region of Enrollment
Brazil
|
13 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
37 Participants
n=7 Participants
|
|
Region of Enrollment
Poland
|
31 Participants
n=99 Participants
|
26 Participants
n=107 Participants
|
30 Participants
n=206 Participants
|
87 Participants
n=7 Participants
|
|
Region of Enrollment
Italy
|
21 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
65 Participants
n=7 Participants
|
|
Region of Enrollment
Israel
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
9 Participants
n=7 Participants
|
|
Region of Enrollment
France
|
12 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
36 Participants
n=7 Participants
|
|
Region of Enrollment
Lithuania
|
13 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
45 Participants
n=7 Participants
|
|
Region of Enrollment
Estonia
|
15 Participants
n=99 Participants
|
17 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
50 Participants
n=7 Participants
|
|
Region of Enrollment
Croatia
|
6 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
16 Participants
n=7 Participants
|
|
MMSE total score at screening
|
17.6 units on a scale
STANDARD_DEVIATION 2.9 • n=99 Participants
|
17.4 units on a scale
STANDARD_DEVIATION 3.0 • n=107 Participants
|
17.5 units on a scale
STANDARD_DEVIATION 3.0 • n=206 Participants
|
17.5 units on a scale
STANDARD_DEVIATION 3.0 • n=7 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine, and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Change from baseline to Week 24 in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score. The Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-cog) is a 11-item neuropsychological test that assess the severity of cognitive impairment. The items determine the patient's orientation, memory, language, and praxis. Total score of the 11 items range from 0 to 70 (lower score indicates lower cognitive impairment).
Outcome measures
| Measure |
Placebo
n=278 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=282 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=275 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in Cognition
|
0.64 units on a scale
Standard Error 0.39
|
0.55 units on a scale
Standard Error 0.39
|
1.27 units on a scale
Standard Error 0.39
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine, and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Change from baseline to Week 24 in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score. The Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) is a 23-item clinician-rated inventory to assess activities of daily living (conducted with a caregiver or informant). Each item comprises a series of hierarchical sub-questions, ranging from the highest level of independent performance to a complete loss for each activity. Total score of the 23 items ranges from 0 to 78 (higher score indicates lower disability).
Outcome measures
| Measure |
Placebo
n=278 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=282 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=275 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in Daily Functioning
|
-1.39 units on a scale
Standard Error 0.49
|
-1.22 units on a scale
Standard Error 0.49
|
-1.36 units on a scale
Standard Error 0.49
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine, and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score at Week 24. The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change is a semi-structured interview to assess clinically relevant changes in patients with AD. The items determine cognition, behavior, social and daily functioning. Severity at baseline is rated on a 7-point scale from 1 (normal, not ill at all) to 7 (among the most extremely ill patients). The clinically relevant change from baseline is rated on a 7-point scale from 1 (marked improvement) to 7 (marked worsening).
Outcome measures
| Measure |
Placebo
n=277 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=282 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=275 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in Global Impression
|
4.30 units on a scale
Standard Error 0.06
|
4.24 units on a scale
Standard Error 0.06
|
4.35 units on a scale
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine, and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Change from baseline to Week 24 in Neuropsychiatric Inventory (NPI) total score. The Neuropsychiatric Inventory is a 12-item structured interview with a caregiver to assess behavioural disturbances. The NPI comprises 10 behavioural and 2 neurovegetative items. Each item consists of a screening question and several sub-questions that are rated no (not present) or yes (present). Each item is rated for frequency (a 4-point scale from 1 \[occasionally\] to 4 \[very frequent\]) and severity (a 3-point scale from 1 \[mild\] to 3 \[marked\]). The total NPI score is the frequency ratings multiplied by the severity ratings and ranges from 0 to 144 (higher score indicates worse outcome).
Outcome measures
| Measure |
Placebo
n=278 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=282 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=275 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in Behavioural Disturbance
|
-0.31 units on a scale
Standard Error 0.59
|
-0.94 units on a scale
Standard Error 0.59
|
-0.54 units on a scale
Standard Error 0.60
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure/item assessed
Change in single NPI item scores at Week 24. The Neuropsychiatric Inventory is a 12-item structured interview with a caregiver to assess behavioural disturbances. The NPI comprises 10 behavioural and 2 neurovegetative items. Each item consists of a screening question and several sub-questions that are rated no (not present) or yes (present). Each item is then rated for frequency (a 4-point scale from 1 \[occasionally\] to 4 \[very frequent\]) and severity (a 3-point scale from 1 \[mild\] to 3 \[marked\]). Total score for each single NPI item ranges from 0-12 (frequency multiplied by severity), where higher scores represent worse outcome.
Outcome measures
| Measure |
Placebo
n=278 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=282 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=275 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in Individual Behavioural Disturbance Items
Delusions
|
0.01 units on a scale
Standard Error 0.08
|
-0.18 units on a scale
Standard Error 0.08
|
0.00 units on a scale
Standard Error 0.08
|
|
Change in Individual Behavioural Disturbance Items
Hallucinations
|
0.00 units on a scale
Standard Error 0.04
|
-0.06 units on a scale
Standard Error 0.04
|
-0.03 units on a scale
Standard Error 0.04
|
|
Change in Individual Behavioural Disturbance Items
Agitation/aggression
|
0.02 units on a scale
Standard Error 0.11
|
-0.06 units on a scale
Standard Error 0.11
|
-0.06 units on a scale
Standard Error 0.11
|
|
Change in Individual Behavioural Disturbance Items
Depression/dysphoria
|
-0.20 units on a scale
Standard Error 0.10
|
-0.08 units on a scale
Standard Error 0.10
|
-0.14 units on a scale
Standard Error 0.10
|
|
Change in Individual Behavioural Disturbance Items
Anxiety
|
-0.05 units on a scale
Standard Error 0.11
|
-0.06 units on a scale
Standard Error 0.11
|
-0.02 units on a scale
Standard Error 0.11
|
|
Change in Individual Behavioural Disturbance Items
Elation/euphoria
|
0.01 units on a scale
Standard Error 0.04
|
-0.05 units on a scale
Standard Error 0.04
|
-0.02 units on a scale
Standard Error 0.04
|
|
Change in Individual Behavioural Disturbance Items
Apathy/indifference
|
0.00 units on a scale
Standard Error 0.17
|
-0.19 units on a scale
Standard Error 0.17
|
-0.24 units on a scale
Standard Error 0.17
|
|
Change in Individual Behavioural Disturbance Items
Disinhibition
|
0.08 units on a scale
Standard Error 0.09
|
-0.04 units on a scale
Standard Error 0.09
|
0.02 units on a scale
Standard Error 0.09
|
|
Change in Individual Behavioural Disturbance Items
Irritability/lability
|
0.03 units on a scale
Standard Error 0.12
|
-0.05 units on a scale
Standard Error 0.12
|
-0.17 units on a scale
Standard Error 0.12
|
|
Change in Individual Behavioural Disturbance Items
Aberrant motor behaviour
|
-0.03 units on a scale
Standard Error 0.14
|
0.06 units on a scale
Standard Error 0.14
|
0.12 units on a scale
Standard Error 0.14
|
|
Change in Individual Behavioural Disturbance Items
Sleep
|
-0.04 units on a scale
Standard Error 0.12
|
-0.07 units on a scale
Standard Error 0.12
|
0.12 units on a scale
Standard Error 0.12
|
|
Change in Individual Behavioural Disturbance Items
Appetite/eating disorder
|
-0.14 units on a scale
Standard Error 0.14
|
-0.30 units on a scale
Standard Error 0.14
|
-0.07 units on a scale
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome/item measure assessed
Change from baseline to Week 24 in NPI anxiety item score in patients with an NPI anxiety item score of at least 2 at baseline The Neuropsychiatric Inventory is a 12-item structured interview with a caregiver to assess behavioural disturbances. The NPI comprises 10 behavioural and 2 neurovegetative items. Each item consists of a screening question and several sub-questions that are rated no (not present) or yes (present). Each item is then rated for frequency (a 4-point scale from 1 \[occasionally\] to 4 \[very frequent\]) and severity (a 3-point scale from 1 \[mild\] to 3 \[marked\]). The total score for the NPI anxiety item ranges from 0-12 (frequency multiplied by severity), where a higher score represents a worse outcome.
Outcome measures
| Measure |
Placebo
n=71 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=56 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=61 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline
|
-1.48 units on a scale
Standard Error 0.38
|
-1.82 units on a scale
Standard Error 0.40
|
-1.69 units on a scale
Standard Error 0.40
|
SECONDARY outcome
Timeframe: Week 24Population: All patients who took at least one dose of placebo or idalopirdine and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Clinical response at Week 24 (based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes \[change in ADAS-cog below or equal to -4, change in ADCS-ADL23 at least 0, and ADCS-CGIC below or equal to 4\])
Outcome measures
| Measure |
Placebo
n=255 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=257 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=249 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Number of Participants With Clinical Improvement
|
20 Participants
|
33 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: Week 24Population: All patients who took at least one dose of placebo or idalopirdine and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Clinical worsening at Week 24 (Based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes \[change in ADAS-cog above or equal to 4, change in ADCS-ADL23 below 0, and ADCS-CGIC above 4\])
Outcome measures
| Measure |
Placebo
n=255 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=257 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=249 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Number of Participants With Clinical Worsening
|
27 Participants
|
28 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Change from baseline to Week 24 in Mini Mental State Examination (MMSE). The Mini Mental State Examination (MMSE) is an 11-item test to assess the cognitive aspects of mental function. The subtests assess orientation, memory, attention, language, and visual construction. The scores for each item is dichotomous (1 = response is correct, 0 = response is incorrect). Total score of the 11 items ranges from 0 to 30 (higher score indicates lower deficit).
Outcome measures
| Measure |
Placebo
n=258 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=257 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=248 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in Cognitive Aspects of Mental Function
|
-0.24 units on a scale
Standard Error 0.21
|
-0.45 units on a scale
Standard Error 0.21
|
-0.34 units on a scale
Standard Error 0.21
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Change from baseline to Week 24 in EuroQol 5-dimensional (EQ-5D) utility score The EQ-5D is a patient-reported assessment that measures the patient's well-being. It consists of an utility score based on 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a Visual Analogue Scale (VAS). Each descriptive item is rated on a 3-point index ranging from 1 (no problems) to 3 (extreme problems) that is used for calculating a single summary index (from 0 to 1). A higher EQ-5D score indicates a worse outcome.
Outcome measures
| Measure |
Placebo
n=274 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=275 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=266 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in Health-related Quality of Life (EQ-5D) Utility Score
|
0.03 units on a scale
Standard Error 0.01
|
0.02 units on a scale
Standard Error 0.01
|
0.01 units on a scale
Standard Error 0.01
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: All patients who took at least one dose of placebo or idalopirdine and who had a valid baseline assessment and at least one valid post-baseline assessment of the primary outcome measure in the 24-week treatment period (Full-analysis Set). For secondary outcome measures, the number of participants who had the respective outcome measure assessed.
Change from baseline to Week 24 in EQ-5D Visual Analogue Scale (EQ-5D VAS). The EQ-5D is a patient-reported assessment that measures the patient's well-being. It consists of an utility score based on 5 descriptive items (mobility, self-care, usual activities, pain/discomfort, and depression/anxiety) and a Visual Analogue Scale (VAS). The VAS ranges from 0 (worst imaginable health state) to 100 (best imaginable health state).
Outcome measures
| Measure |
Placebo
n=274 Participants
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=274 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=266 Participants
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Change in Health-related Quality of Life (EQ-5D VAS)
|
1.35 units on a scale
Standard Error 0.99
|
1.87 units on a scale
Standard Error 0.99
|
1.00 units on a scale
Standard Error 1.01
|
Adverse Events
Placebo
Idalopirdine 10 mg
Idalopirdine 30 mg
Serious adverse events
| Measure |
Placebo
n=282 participants at risk
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=285 participants at risk
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=281 participants at risk
Idalopirdine adjunct to 20 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphadenitis
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Cardiac disorders
Atrioventricular block complete
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Cardiac disorders
Cardiac arrest
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Cardiac disorders
Cardiac failure
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.71%
2/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Gastrointestinal disorders
Dysphagia
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Gastrointestinal disorders
Pancreatitis
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
General disorders
Gait disturbance
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.71%
2/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Infections and infestations
Urinary tract infection bacterial
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal cancer
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Carotid sinus syndrome
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.70%
2/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Dementia
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Embolic stroke
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Encephalopathy
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Ischaemic stroke
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Syncope
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Aggression
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Delirium
|
0.71%
2/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Depressive symptom
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Hallucination
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Hallucinations, mixed
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Psychiatric disorders
Suicidal ideation
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.35%
1/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/101 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/113 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.89%
1/112 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal haemorrhage
|
0.35%
1/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.00%
0/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
0.36%
1/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
Other adverse events
| Measure |
Placebo
n=282 participants at risk
Placebo adjunct to 10 mg Donepezil
Placebo: Once daily, matching placebo capsules, orally
|
Idalopirdine 10 mg
n=285 participants at risk
Idalopirdine adjunct to 10 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
Idalopirdine 30 mg
n=281 participants at risk
Idalopirdine adjunct to 20 mg Donepezil
Idalopirdine: Once daily, encapsulated tablets, orally
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Accidental overdose
|
11.7%
33/282 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
9.1%
26/285 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
11.0%
31/281 • Baseline to end of study at Week 24
Treatment-Emergent Adverse Events are reported in this section
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place