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Trial record 18 of 31 for:    alzheimer dijon

Idalopirdine in Patients With Mild-moderate Alzheimer's Disease Treated With Donepezil (STARBEAM)

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ClinicalTrials.gov Identifier: NCT02006641
Recruitment Status : Completed
First Posted : December 10, 2013
Results First Posted : February 20, 2018
Last Update Posted : February 20, 2018
Sponsor:
Collaborator:
Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
H. Lundbeck A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: Placebo
Drug: Idalopirdine
Enrollment 858
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Period Title: Overall Study
Started 284 290 284
Treated 282 285 281
Completed 258 257 248
Not Completed 26 33 36
Reason Not Completed
Withdrawal before treatment             2             5             3
Adverse Event             15             11             15
Protocol Violation             0             2             2
Lost to Follow-up             0             1             0
Withdrawal by Subject             7             12             11
Other reason: patient didn't show up             1             0             0
Other reason:patient didn't want to come             0             0             1
Other reason: patient has moved             1             0             1
Other reason: caregiver in hospital             0             1             0
Other reason: patient's wife has died             0             0             1
Other reason: hospitalisation             0             1             0
Other reason: caregiver impossibility             0             0             1
Other reason: protocol non-compliance             0             0             1
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg Total
Hide Arm/Group Description

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Total of all reporting groups
Overall Number of Baseline Participants 282 285 281 848
Hide Baseline Analysis Population Description
A total of 858 patients were randomized into the study but 10 patients were not treated (did not receive IMP). The baseline analysis population only consist of patients who have been treated.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 282 participants 285 participants 281 participants 848 participants
73.4  (8.3) 74.9  (8.1) 75.0  (8.0) 74.4  (8.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 282 participants 285 participants 281 participants 848 participants
Female
181
  64.2%
172
  60.4%
169
  60.1%
522
  61.6%
Male
101
  35.8%
113
  39.6%
112
  39.9%
326
  38.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 282 participants 285 participants 281 participants 848 participants
Hispanic or Latino
10
   3.5%
11
   3.9%
10
   3.6%
31
   3.7%
Not Hispanic or Latino
42
  14.9%
47
  16.5%
41
  14.6%
130
  15.3%
Unknown or Not Reported
230
  81.6%
227
  79.6%
230
  81.9%
687
  81.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 282 participants 285 participants 281 participants 848 participants
American Indian or Alaska Native NA [1]  NA [1]  NA [1]  NA [2] 
Asian
20
   7.1%
24
   8.4%
24
   8.5%
68
   8.0%
Native Hawaiian or Other Pacific Islander NA [1]  NA [1]  NA [1]  NA [2] 
Black or African American
6
   2.1%
6
   2.1%
4
   1.4%
16
   1.9%
White
250
  88.7%
249
  87.4%
244
  86.8%
743
  87.6%
More than one race NA [1]  NA [1]  NA [1]  NA [2] 
Unknown or Not Reported
6
   2.1%
6
   2.1%
9
   3.2%
21
   2.5%
[1]
Information has not been collected
[2]
Total not calculated because data are not available (NA) in one or more arms.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 282 participants 285 participants 281 participants 848 participants
Argentina
23
   8.2%
26
   9.1%
24
   8.5%
73
   8.6%
Hungary
7
   2.5%
4
   1.4%
4
   1.4%
15
   1.8%
Czechia
16
   5.7%
15
   5.3%
17
   6.0%
48
   5.7%
United States
54
  19.1%
58
  20.4%
52
  18.5%
164
  19.3%
United Kingdom
29
  10.3%
28
   9.8%
25
   8.9%
82
   9.7%
Portugal
4
   1.4%
6
   2.1%
5
   1.8%
15
   1.8%
Canada
11
   3.9%
9
   3.2%
10
   3.6%
30
   3.5%
South Korea
14
   5.0%
16
   5.6%
16
   5.7%
46
   5.4%
Finland
4
   1.4%
5
   1.8%
4
   1.4%
13
   1.5%
Taiwan
6
   2.1%
5
   1.8%
6
   2.1%
17
   2.0%
Brazil
13
   4.6%
13
   4.6%
11
   3.9%
37
   4.4%
Poland
31
  11.0%
26
   9.1%
30
  10.7%
87
  10.3%
Italy
21
   7.4%
22
   7.7%
22
   7.8%
65
   7.7%
Israel
3
   1.1%
3
   1.1%
3
   1.1%
9
   1.1%
France
12
   4.3%
12
   4.2%
12
   4.3%
36
   4.2%
Lithuania
13
   4.6%
16
   5.6%
16
   5.7%
45
   5.3%
Estonia
15
   5.3%
17
   6.0%
18
   6.4%
50
   5.9%
Croatia
6
   2.1%
4
   1.4%
6
   2.1%
16
   1.9%
MMSE total score at screening   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 282 participants 285 participants 281 participants 848 participants
17.6  (2.9) 17.4  (3.0) 17.5  (3.0) 17.5  (3.0)
[1]
Measure Description: 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).
1.Primary Outcome
Title Change in Cognition
Hide Description

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).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 278 282 275
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.64  (0.39) 0.55  (0.39) 1.27  (0.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 10 mg
Comments For demonstrating efficacy of a dose, change in cognition (ADAS-cog) and either change in daily functioning (ADCS-ADL23) or change in global clinical impression (ADCS-CGIC) at Week 24 had to show statistically significant favourable differences compared to placebo at Week 24. Overall, type 1 error was controlled at 5% by multiplicity adjustment. Testing of the doses was done in a gated manner, first testing 30 mg at a 5% significance level, and only if found efficacious, then moving on to 10 mg.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments Corrected for multiplicity
Method Mixed Models Analysis
Comments Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-1.10 to 0.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.51
Estimation Comments A negative mean difference indicates a treatment effect in favour of idalopirdine
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 30 mg
Comments For demonstrating efficacy of a dose, change in cognition (ADAS-cog) and either change in daily functioning (ADCS-ADL23) or change in global clinical impression (ADCS-CGIC) at Week 24 had to show statistically significant favourable differences compared to placebo at Week 24. Overall, type 1 error was controlled at 5% by multiplicity adjustment. Testing of the doses was done in a gated manner, first testing 30 mg at a 5% significance level, and only if found efficacious, then moving on to 10 mg.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2223
Comments Corrected for multiplicity according to the multiple testing procedure
Method Mixed Models Analysis
Comments Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
-0.38 to 1.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.52
Estimation Comments A negative mean difference indicates a treatment effect in favour of idalopirdine.
2.Secondary Outcome
Title Change in Daily Functioning
Hide Description

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).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 278 282 275
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.39  (0.49) -1.22  (0.49) -1.36  (0.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 10 mg
Comments For demonstrating efficacy of a dose, change in cognition (ADAS-cog) and either change in daily functioning (ADCS-ADL23) or change in global clinical impression (ADCS-CGIC) at Week 24 had to show statistically significant favourable differences compared to placebo at Week 24. Overall, type 1 error was controlled at 5% by multiplicity adjustment. Testing of the doses was done in a gated manner, first testing 30 mg at a 5% significance level, and only if found efficacious, then moving on to 10 mg.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments Corrected for multiplicity according to the multiple testing procedure
Method Mixed Models Analysis
Comments Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-1.11 to 1.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.65
Estimation Comments A positive mean difference indicates a treatment effect in favour of idalopirdine.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 30 mg
Comments For demonstrating efficacy of a dose, change in cognition (ADAS-cog) and either change in daily functioning (ADCS-ADL23) or change in global clinical impression (ADCS-CGIC) at Week 24 had to show statistically significant favourable differences compared to placebo at Week 24. Overall, type 1 error was controlled at 5% by multiplicity adjustment. Testing of the doses was done in a gated manner, first testing 30 mg at a 5% significance level, and only if found efficacious, then moving on to 10 mg.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments Corrected for multiplicity according to the multiple testing procedure
Method Mixed Models Analysis
Comments Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-1.27 to 1.33
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.66
Estimation Comments A positive mean difference indicates a treatment effect in favour of idalopirdine.
3.Secondary Outcome
Title Change in Global Impression
Hide Description

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).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 277 282 275
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
4.30  (0.06) 4.24  (0.06) 4.35  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 10 mg
Comments For demonstrating efficacy of a dose, change in cognition (ADAS-cog) and either change in daily functioning (ADCS-ADL23) or change in global clinical impression (ADCS-CGIC) at Week 24 had to show statistically significant favourable differences compared to placebo at Week 24. Overall, type 1 error was controlled at 5% by multiplicity adjustment. Testing of the doses was done in a gated manner, first testing 30 mg at a 5% significance level, and only if found efficacious, then moving on to 10 mg.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments Corrected for multiplicity according to the multiple testing procedure
Method Mixed Models Analysis
Comments Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.23 to 0.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.08
Estimation Comments A negative mean difference indicates a treatment effect in favour of idalopirdine.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 30 mg
Comments For demonstrating efficacy of a dose, change in cognition (ADAS-cog) and either change in daily functioning (ADCS-ADL23) or change in global clinical impression (ADCS-CGIC) at Week 24 had to show statistically significant favourable differences compared to placebo at Week 24. Overall, type 1 error was controlled at 5% by multiplicity adjustment. Testing of the doses was done in a gated manner, first testing 30 mg at a 5% significance level, and only if found efficacious, then moving on to 10 mg.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments Corrected for multiplicity according to the multiple testing procedure
Method Mixed Models Analysis
Comments Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.12 to 0.21
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.09
Estimation Comments A negative mean difference indicates a treatment effect in favour of idalopirdine.
4.Secondary Outcome
Title Change in Behavioural Disturbance
Hide Description

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).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 278 282 275
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.31  (0.59) -0.94  (0.59) -0.54  (0.60)
5.Secondary Outcome
Title Change in Individual Behavioural Disturbance Items
Hide Description

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.

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 278 282 275
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Delusions 0.01  (0.08) -0.18  (0.08) 0.00  (0.08)
Hallucinations 0.00  (0.04) -0.06  (0.04) -0.03  (0.04)
Agitation/aggression 0.02  (0.11) -0.06  (0.11) -0.06  (0.11)
Depression/dysphoria -0.20  (0.10) -0.08  (0.10) -0.14  (0.10)
Anxiety -0.05  (0.11) -0.06  (0.11) -0.02  (0.11)
Elation/euphoria 0.01  (0.04) -0.05  (0.04) -0.02  (0.04)
Apathy/indifference 0.00  (0.17) -0.19  (0.17) -0.24  (0.17)
Disinhibition 0.08  (0.09) -0.04  (0.09) 0.02  (0.09)
Irritability/lability 0.03  (0.12) -0.05  (0.12) -0.17  (0.12)
Aberrant motor behaviour -0.03  (0.14) 0.06  (0.14) 0.12  (0.14)
Sleep -0.04  (0.12) -0.07  (0.12) 0.12  (0.12)
Appetite/eating disorder -0.14  (0.14) -0.30  (0.14) -0.07  (0.14)
6.Secondary Outcome
Title Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline
Hide Description

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.

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 71 56 61
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.48  (0.38) -1.82  (0.40) -1.69  (0.40)
7.Secondary Outcome
Title Number of Participants With Clinical Improvement
Hide Description 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])
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 255 257 249
Measure Type: Count of Participants
Unit of Measure: Participants
20
   7.8%
33
  12.8%
22
   8.8%
8.Secondary Outcome
Title Number of Participants With Clinical Worsening
Hide Description 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])
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 255 257 249
Measure Type: Count of Participants
Unit of Measure: Participants
27
  10.6%
28
  10.9%
27
  10.8%
9.Secondary Outcome
Title Change in Cognitive Aspects of Mental Function
Hide Description 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).
Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 258 257 248
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.24  (0.21) -0.45  (0.21) -0.34  (0.21)
10.Secondary Outcome
Title Change in Health-related Quality of Life (EQ-5D) Utility Score
Hide Description

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.

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 274 275 266
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.03  (0.01) 0.02  (0.01) 0.01  (0.01)
11.Secondary Outcome
Title Change in Health-related Quality of Life (EQ-5D VAS)
Hide Description

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).

Time Frame Baseline and Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description:

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Overall Number of Participants Analyzed 274 274 266
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
1.35  (0.99) 1.87  (0.99) 1.00  (1.01)
Time Frame Baseline to end of study at Week 24
Adverse Event Reporting Description Treatment-Emergent Adverse Events are reported in this section
 
Arm/Group Title Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Hide Arm/Group Description

Placebo adjunct to 10 mg Donepezil

Placebo: Once daily, matching placebo capsules, orally

Idalopirdine adjunct to 10 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

Idalopirdine adjunct to 20 mg Donepezil

Idalopirdine: Once daily, encapsulated tablets, orally

All-Cause Mortality
Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/282 (0.35%)   0/285 (0.00%)   1/281 (0.36%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/282 (4.26%)   13/285 (4.56%)   15/281 (5.34%) 
Blood and lymphatic system disorders       
Lymphadenitis  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Cardiac disorders       
Acute myocardial infarction  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Angina pectoris  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
Atrioventricular block complete  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Bradycardia  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
Cardiac arrest  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Cardiac failure  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Myocardial infarction  1  0/282 (0.00%)  0/285 (0.00%)  2/281 (0.71%) 
Gastrointestinal disorders       
Dysphagia  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Gastrooesophageal reflux disease  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Inguinal hernia  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Pancreatitis  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
General disorders       
Gait disturbance  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Hepatobiliary disorders       
Bile duct obstruction  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Cholelithiasis  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Infections and infestations       
Pneumonia bacterial  1  0/282 (0.00%)  0/285 (0.00%)  2/281 (0.71%) 
Urinary tract infection bacterial  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Injury, poisoning and procedural complications       
Cervical vertebral fracture  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
Rib fracture  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Anal cancer  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Bladder transitional cell carcinoma  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
Nervous system disorders       
Carotid sinus syndrome  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
Cerebrovascular accident  1  0/282 (0.00%)  2/285 (0.70%)  0/281 (0.00%) 
Dementia  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Embolic stroke  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
Encephalopathy  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Epilepsy  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Ischaemic stroke  1  1/282 (0.35%)  1/285 (0.35%)  0/281 (0.00%) 
Syncope  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Transient ischaemic attack  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
Psychiatric disorders       
Aggression  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
Delirium  1  2/282 (0.71%)  0/285 (0.00%)  1/281 (0.36%) 
Depressive symptom  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Hallucination  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Hallucinations, mixed  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Suicidal ideation  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Urinary retention  1  0/282 (0.00%)  1/285 (0.35%)  0/281 (0.00%) 
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  0/101 (0.00%)  0/113 (0.00%)  1/112 (0.89%) 
Respiratory, thoracic and mediastinal disorders       
Laryngeal haemorrhage  1  1/282 (0.35%)  0/285 (0.00%)  0/281 (0.00%) 
Vascular disorders       
Circulatory collapse  1  0/282 (0.00%)  0/285 (0.00%)  1/281 (0.36%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Idalopirdine 10 mg Idalopirdine 30 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/282 (11.70%)   26/285 (9.12%)   31/281 (11.03%) 
Injury, poisoning and procedural complications       
Accidental overdose  1  33/282 (11.70%)  26/285 (9.12%)  31/281 (11.03%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Email contact via
Organization: H. Lundbeck A/S
Phone: +4536301311
Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT02006641     History of Changes
Other Study ID Numbers: 14862A
2012-004764-22 ( EudraCT Number )
First Submitted: December 5, 2013
First Posted: December 10, 2013
Results First Submitted: December 19, 2017
Results First Posted: February 20, 2018
Last Update Posted: February 20, 2018