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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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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


Participant Flow:   Overall Study
    Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg
STARTED   284   290   284 
Treated   282   285   281 
COMPLETED   258   257   248 
NOT COMPLETED   26   33   36 
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 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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

Total Total of all reporting groups

Baseline Measures
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 282   285   281   848 
Age 
[Units: Years]
Mean (Standard Deviation)
 73.4  (8.3)   74.9  (8.1)   75.0  (8.0)   74.4  (8.1) 
Sex: Female, Male 
[Units: Participants]
Count of 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) 
[Units: Participants]
Count of 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) [1] [2] 
[Units: Participants]
Count of 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 
[Units: Participants]
Count of Participants
       
Argentina   23   26   24   73 
Hungary   7   4   4   15 
Czechia   16   15   17   48 
United States   54   58   52   164 
United Kingdom   29   28   25   82 
Portugal   4   6   5   15 
Canada   11   9   10   30 
South Korea   14   16   16   46 
Finland   4   5   4   13 
Taiwan   6   5   6   17 
Brazil   13   13   11   37 
Poland   31   26   30   87 
Italy   21   22   22   65 
Israel   3   3   3   9 
France   12   12   12   36 
Lithuania   13   16   16   45 
Estonia   15   17   18   50 
Croatia   6   4   6   16 
MMSE total score at screening [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 17.6  (2.9)   17.4  (3.0)   17.5  (3.0)   17.5  (3.0) 
[1] 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

1.  Primary:   Change in Cognition   [ Time Frame: Baseline and Week 24 ]

Measure Type Primary
Measure Title Change in Cognition
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   278   282   275 
Change in Cognition 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 0.64  (0.39)   0.55  (0.39)   1.27  (0.39) 


Statistical Analysis 1 for Change in Cognition
Groups [1] Placebo vs. Idalopirdine 10 mg
Statistical Test Type [2] Superiority
Statistical Method [3] Mixed Models Analysis
P Value [4] 1.000
Mean Difference (Final Values) [5] -0.09
95% Confidence Interval -1.10 to 0.92
Standard Error of the Mean (0.51)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Corrected for multiplicity
[5] Other relevant estimation information:
  A negative mean difference indicates a treatment effect in favour of idalopirdine

Statistical Analysis 2 for Change in Cognition
Groups [1] Placebo vs. Idalopirdine 30 mg
Statistical Test Type [2] Superiority
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.2223
Mean Difference (Final Values) [5] 0.63
95% Confidence Interval -0.38 to 1.65
Standard Error of the Mean (0.52)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Corrected for multiplicity according to the multiple testing procedure
[5] Other relevant estimation information:
  A negative mean difference indicates a treatment effect in favour of idalopirdine.



2.  Secondary:   Change in Daily Functioning   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change in Daily Functioning
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   278   282   275 
Change in Daily Functioning 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 -1.39  (0.49)   -1.22  (0.49)   -1.36  (0.49) 


Statistical Analysis 1 for Change in Daily Functioning
Groups [1] Placebo vs. Idalopirdine 10 mg
Statistical Test Type [2] Superiority
Statistical Method [3] Mixed Models Analysis
P Value [4] 1.000
Mean Difference (Net) [5] 0.17
95% Confidence Interval -1.11 to 1.46
Standard Error of the Mean (0.65)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Corrected for multiplicity according to the multiple testing procedure
[5] Other relevant estimation information:
  A positive mean difference indicates a treatment effect in favour of idalopirdine.

Statistical Analysis 2 for Change in Daily Functioning
Groups [1] Placebo vs. Idalopirdine 30 mg
Statistical Test Type [2] Superiority
Statistical Method [3] Mixed Models Analysis
P Value [4] 1.000
Mean Difference (Final Values) [5] 0.03
95% Confidence Interval -1.27 to 1.33
Standard Error of the Mean (0.66)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Corrected for multiplicity according to the multiple testing procedure
[5] Other relevant estimation information:
  A positive mean difference indicates a treatment effect in favour of idalopirdine.



3.  Secondary:   Change in Global Impression   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change in Global Impression
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   277   282   275 
Change in Global Impression 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 4.30  (0.06)   4.24  (0.06)   4.35  (0.06) 


Statistical Analysis 1 for Change in Global Impression
Groups [1] Placebo vs. Idalopirdine 10 mg
Statistical Test Type [2] Superiority
Statistical Method [3] Mixed Models Analysis
P Value [4] 1.000
Mean Difference (Final Values) [5] -0.07
95% Confidence Interval -0.23 to 0.10
Standard Error of the Mean (0.08)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Corrected for multiplicity according to the multiple testing procedure
[5] Other relevant estimation information:
  A negative mean difference indicates a treatment effect in favour of idalopirdine.

Statistical Analysis 2 for Change in Global Impression
Groups [1] Placebo vs. Idalopirdine 30 mg
Statistical Test Type [2] Superiority
Statistical Method [3] Mixed Models Analysis
P Value [4] 1.000
Mean Difference (Final Values) [5] 0.05
95% Confidence Interval -0.12 to 0.21
Standard Error of the Mean (0.09)
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  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.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  Treatment, country, MMSE stratum, week as fixed effects, baseline score, treatment-by-week, MMSE stratum-by-week, and baseline-by-week interactions
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Corrected for multiplicity according to the multiple testing procedure
[5] Other relevant estimation information:
  A negative mean difference indicates a treatment effect in favour of idalopirdine.



4.  Secondary:   Change in Behavioural Disturbance   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change in Behavioural Disturbance
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   278   282   275 
Change in Behavioural Disturbance 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 -0.31  (0.59)   -0.94  (0.59)   -0.54  (0.60) 

No statistical analysis provided for Change in Behavioural Disturbance



5.  Secondary:   Change in Individual Behavioural Disturbance Items   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change in Individual Behavioural Disturbance Items
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   278   282   275 
Change in Individual Behavioural Disturbance Items 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
     
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) 

No statistical analysis provided for Change in Individual Behavioural Disturbance Items



6.  Secondary:   Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   71   56   61 
Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 -1.48  (0.38)   -1.82  (0.40)   -1.69  (0.40) 

No statistical analysis provided for Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline



7.  Secondary:   Number of Participants With Clinical Improvement   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Number of Participants With Clinical Improvement
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   255   257   249 
Number of Participants With Clinical Improvement 
[Units: Participants]
Count of Participants
 20   33   22 

No statistical analysis provided for Number of Participants With Clinical Improvement



8.  Secondary:   Number of Participants With Clinical Worsening   [ Time Frame: Week 24 ]

Measure Type Secondary
Measure Title Number of Participants With Clinical Worsening
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   255   257   249 
Number of Participants With Clinical Worsening 
[Units: Participants]
Count of Participants
 27   28   27 

No statistical analysis provided for Number of Participants With Clinical Worsening



9.  Secondary:   Change in Cognitive Aspects of Mental Function   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change in Cognitive Aspects of Mental Function
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   258   257   248 
Change in Cognitive Aspects of Mental Function 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 -0.24  (0.21)   -0.45  (0.21)   -0.34  (0.21) 

No statistical analysis provided for Change in Cognitive Aspects of Mental Function



10.  Secondary:   Change in Health-related Quality of Life (EQ-5D) Utility Score   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change in Health-related Quality of Life (EQ-5D) Utility Score
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   274   275   266 
Change in Health-related Quality of Life (EQ-5D) Utility Score 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 0.03  (0.01)   0.02  (0.01)   0.01  (0.01) 

No statistical analysis provided for Change in Health-related Quality of Life (EQ-5D) Utility Score



11.  Secondary:   Change in Health-related Quality of Life (EQ-5D VAS)   [ Time Frame: Baseline and Week 24 ]

Measure Type Secondary
Measure Title Change in Health-related Quality of Life (EQ-5D VAS)
Measure 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  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups
  Description
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


Measured Values
   Placebo   Idalopirdine 10 mg   Idalopirdine 30 mg 
Participants Analyzed   274   274   266 
Change in Health-related Quality of Life (EQ-5D VAS) 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
 1.35  (0.99)   1.87  (0.99)   1.00  (1.01) 

No statistical analysis provided for Change in Health-related Quality of Life (EQ-5D VAS)




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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
e-mail: LundbeckClinicalTrials@lundbeck.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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