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Study of Idalopirdine in Patients With Mild - Moderate Alzheimer's Disease Treated With Donepezil (STARSHINE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01955161
Recruitment Status : Completed
First Posted : October 7, 2013
Results First Posted : September 19, 2017
Last Update Posted : September 19, 2017
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 933
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Idalopirdine 30 mg Idalopirdine 60 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 310 313 310
Treated 308 313 309
Completed 283 288 275
Not Completed 27 25 35
Reason Not Completed
Withdrawal before treatment             2             0             1
Adverse Event             10             14             15
Death             1             1             3
Withdrawal by Subject             9             8             12
Protocol Violation             2             0             0
Other reason: physician decision             0             1             1
Other reason: disallowed medication             1             0             1
Other reason: caregiver unavailable             1             0             0
Other reason: moved to nursing home             0             1             0
Other reason: insufficient compliance             0             0             1
Other reason: primary biliary cirrhosis             1             0             0
Other reason: patient's will             0             0             1
Arm/Group Title Placebo Idalopirdine 30 mg Idalopirdine 60 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 308 313 309 930
Hide Baseline Analysis Population Description
A total of 933 patients were randomized into the study but 3 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 308 participants 313 participants 309 participants 930 participants
73.8  (8.0) 74.0  (8.8) 73.7  (8.6) 73.8  (8.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 313 participants 309 participants 930 participants
Female
198
  64.3%
208
  66.5%
201
  65.0%
607
  65.3%
Male
110
  35.7%
105
  33.5%
108
  35.0%
323
  34.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 313 participants 309 participants 930 participants
Hispanic or Latino
2
   0.6%
1
   0.3%
1
   0.3%
4
   0.4%
Not Hispanic or Latino
40
  13.0%
44
  14.1%
41
  13.3%
125
  13.4%
Unknown or Not Reported
266
  86.4%
268
  85.6%
267
  86.4%
801
  86.1%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 308 participants 313 participants 309 participants 930 participants
American Indian or Alaska Native NA [1]  NA [1]  NA [1]  NA [2] 
Asian
1
   0.3%
1
   0.3%
3
   1.0%
5
   0.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
2
   0.6%
1
   0.3%
3
   0.3%
Black or African American
2
   0.6%
4
   1.3%
2
   0.6%
8
   0.9%
White
283
  91.9%
287
  91.7%
284
  91.9%
854
  91.8%
More than one race NA [1]  NA [1]  NA [1]  NA [2] 
Unknown or Not Reported
22
   7.1%
19
   6.1%
19
   6.1%
60
   6.5%
[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: Number
Unit of measure:  Participants
Number Analyzed 308 participants 313 participants 309 participants 930 participants
Argentina 24 25 21 70
Romania 4 2 4 10
Czech Republic 36 35 38 109
United States 42 45 43 130
Ukraine 21 20 20 61
Spain 19 22 19 60
Canada 15 12 13 40
Belgium 6 7 5 18
Denmark 4 4 5 13
Poland 25 24 24 73
Italy 13 12 11 36
South Africa 18 19 20 57
Bulgaria 22 19 19 60
Chile 28 30 31 89
France 14 15 17 46
Germany 17 22 19 58
MMSE total score at screening   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 308 participants 313 participants 309 participants 930 participants
17.4  (2.9) 17.2  (3.1) 17.4  (2.9) 17.4  (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 to Week 24
Hide 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 on 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 30 mg Idalopirdine 60 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 304 310 308
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.13  (0.35) 0.47  (0.35) 0.18  (0.35)
Hide Statistical Analysis 1
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) had to show statistically significant favourable differences compared to placebo at Week 24. Multiple testing procedures were used to control the overall type 1 error at 5%. The null hypothesis of no difference in mean change from baseline in ADAS-cog total score at Week 24 was tested for each dose at significance level 2.5%.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9591
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 0.33
Confidence Interval (2-Sided) 95%
-0.59 to 1.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.47
Estimation Comments A negative mean difference indicates a treatment effect in favour of idalopirdine
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 60 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) had to show statistically significant favourable differences compared to placebo at Week 24. Multiple testing procedures were used to control the overall type 1 error at 5%. The null hypothesis of no difference in mean change from baseline in ADAS-cog total score at Week 24 was tested for each dose at significance level 2.5%.
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%
-0.88 to 0.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.47
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 to Week 24
Hide 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 on 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 30 mg Idalopirdine 60 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 304 310 308
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.03  (0.49) -2.12  (0.48) -2.02  (0.49)
Hide Statistical Analysis 1
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) had to show statistically significant favourable differences compared to placebo at Week 24. Multiple testing procedures were used to control the overall type 1 error at 5%. The null hypothesis of no difference in mean change from baseline in ADAS-cog total score at Week 24 was tested for each dose at significance level 2.5%.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments Corrected for multiplicity according toe 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 -0.08
Confidence Interval (2-Sided) 95%
-1.37 to 1.21
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.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 60 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) had to show statistically significant favourable differences compared to placebo at Week 24. Multiple testing procedures were used to control the overall type 1 error at 5%. The null hypothesis of no difference in mean change from baseline in ADAS-cog total score at Week 24 was tested for each dose at significance level 2.5%.
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 0.01
Confidence Interval (2-Sided) 95%
-1.29 to 1.31
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 to Week 24
Hide 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 on 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 30 mg Idalopirdine 60 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 303 309 307
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
4.29  (0.07) 4.32  (0.07) 4.13  (0.07)
Hide Statistical Analysis 1
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) had to show statistically significant favourable differences compared to placebo at Week 24. Multiple testing procedures were used to control the overall type 1 error at 5%. The null hypothesis of no difference in mean change from baseline in ADAS-cog total score at Week 24 was tested for each dose at significance level 2.5%.
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%
-0.15 to 0.20
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.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Idalopirdine 60 mg
Comments For demonstrating efficacy of a dose, ADAS-cog total score and either ADCS-ADL23 total score or ADCS CGIC had to show statistically significant favourable differences compared to placebo at Week 24. Multiple testing procedures were used to control the overall type 1 error at 5%. The null hypothesis of no difference in mean change from baseline in ADAS-cog total score at Week 24 was tested for each dose at significance level 2.5%.
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 -0.16
Confidence Interval (2-Sided) 95%
-0.34 to 0.02
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 to Week 24
Hide 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 on 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 30 mg Idalopirdine 60 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 304 310 308
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.21  (0.62) -0.21  (0.62) -0.39  (0.63)
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 to Week 24
Hide 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 on 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 30 mg Idalopirdine 60 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 304 310 308
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Delusions Number Analyzed 304 participants 310 participants 308 participants
-0.11  (0.09) -0.04  (0.09) -0.01  (0.09)
Hallucinations Number Analyzed 304 participants 310 participants 308 participants
0.13  (0.07) 0.03  (0.07) -0.03  (0.07)
Agitation/aggression Number Analyzed 304 participants 310 participants 308 participants
0.01  (0.11) 0.04  (0.11) 0.10  (0.11)
Depression/dysphoria Number Analyzed 304 participants 310 participants 308 participants
0.02  (0.09) -0.06  (0.09) -0.08  (0.10)
Anxiety Number Analyzed 304 participants 310 participants 308 participants
-0.02  (0.11) -0.13  (0.11) -0.13  (0.11)
Elation/euphoria Number Analyzed 304 participants 310 participants 308 participants
0.09  (0.05) 0.03  (0.05) 0.03  (0.05)
Apathy/indifference Number Analyzed 304 participants 310 participants 308 participants
-0.18  (0.15) -0.23  (0.15) -0.27  (0.15)
Disinhibition Number Analyzed 304 participants 310 participants 308 participants
0.05  (0.08) -0.06  (0.08) -0.01  (0.08)
Irritability/lability Number Analyzed 304 participants 310 participants 308 participants
-0.14  (0.12) 0.02  (0.12) 0.00  (0.12)
Aberrant motor behaviour Number Analyzed 304 participants 310 participants 308 participants
0.03  (0.12) 0.33  (0.12) -0.13  (0.13)
Sleep Number Analyzed 304 participants 308 participants 308 participants
0.03  (0.11) 0.01  (0.11) 0.03  (0.11)
Appetite/eating disorder Number Analyzed 304 participants 310 participants 308 participants
-0.08  (0.13) -0.14  (0.13) -0.04  (0.13)
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 to Week 24
Hide 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 on 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 30 mg Idalopirdine 60 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 88 83 76
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.12  (0.30) -1.56  (0.30) -1.64  (0.32)
7.Secondary Outcome
Title 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
Hide 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 on 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 30 mg Idalopirdine 60 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 284 290 278
Measure Type: Count of Participants
Unit of Measure: Participants
34 37 27
8.Secondary Outcome
Title 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
Hide 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 on 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 30 mg Idalopirdine 60 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 284 290 278
Measure Type: Count of Participants
Unit of Measure: Participants
40 42 33
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 to Week 24
Hide 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 on 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 30 mg Idalopirdine 60 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 282 288 274
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.06  (0.16) -0.27  (0.16) 0.27  (0.17)
10.Secondary Outcome
Title Change in Health-related Quality of Life (EQ-5D) Utility Score
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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 to Week 24
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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 on 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 30 mg Idalopirdine 60 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 301 306 304
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.01  (0.01) 0.00  (0.01) 0.00  (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 to Week 24
Hide 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 on 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 30 mg Idalopirdine 60 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 301 307 304
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.40  (1.01) -0.12  (1.01) 0.34  (1.03)
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 30 mg Idalopirdine 60 mg
Hide Arm/Group Description Placebo adjunct to 10 mg Donepezil Idalopirdine adjunct to 10 mg Donezepil Idalopirdine adjunct to 10 mg Donezepil
All-Cause Mortality
Placebo Idalopirdine 30 mg Idalopirdine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/308 (0.32%)   1/313 (0.32%)   3/309 (0.97%) 
Hide Serious Adverse Events
Placebo Idalopirdine 30 mg Idalopirdine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   12/308 (3.90%)   18/313 (5.75%)   20/309 (6.47%) 
Blood and lymphatic system disorders       
Anaemia  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Cardiac disorders       
Acute myocardial infarction  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Angina pectoris  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Atrial fibrillation  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Bradycardia  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Coronary artery disease  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Myocardial infarction  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Sinus node dysfunction  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Gastrointestinal disorders       
Gastrooesophageal reflux disease  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Pancreatitis acute  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
General disorders       
Sudden death  1  0/308 (0.00%)  1/313 (0.32%)  1/309 (0.32%) 
Infections and infestations       
Appendicitis  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Bacterial diarrhoea  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Bacterial sepsis  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Gastroenteritis viral  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Influenza  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Pneumonia  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Pneumonia bacterial  1  2/308 (0.65%)  0/313 (0.00%)  0/309 (0.00%) 
Respiratory tract infection  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Urinary tract infection  1  0/308 (0.00%)  1/313 (0.32%)  1/309 (0.32%) 
Urinary tract infection bacterial  1  1/308 (0.32%)  1/313 (0.32%)  0/309 (0.00%) 
Injury, poisoning and procedural complications       
Femoral neck fracture  1  1/308 (0.32%)  0/313 (0.00%)  1/309 (0.32%) 
Head injury  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Hip fracture  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Radius fracture  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Wrist fracture  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Investigations       
Alanine aminotransferase increased  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Aspartate aminotransferase increased  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Bilirubin conjugated increased  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Blood alkaline phosphatase increased  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Blood bilirubin increased  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
C-reactive protein increased  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Gamma-glutamyltransferase increased  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Musculoskeletal and connective tissue disorders       
Spinal pain  1  2/308 (0.65%)  0/313 (0.00%)  0/309 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Metastases to peritoneum  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Nervous system disorders       
Cerebral arteriosclerosis  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Cerebral haematoma  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Cerebral ischaemia  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Dementia alzheimer's type  1  1/308 (0.32%)  0/313 (0.00%)  0/309 (0.00%) 
Presyncope  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Syncope  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Transient ischaemic attack  1  1/308 (0.32%)  1/313 (0.32%)  1/309 (0.32%) 
Psychiatric disorders       
Confusional state  1  1/308 (0.32%)  0/313 (0.00%)  1/309 (0.32%) 
Delirium  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Impulse-control disorder  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Renal and urinary disorders       
Calculus bladder  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Reproductive system and breast disorders       
Metrorrhagia  1  0/198 (0.00%)  0/208 (0.00%)  1/201 (0.50%) 
Vaginal fistula  1  1/198 (0.51%)  0/208 (0.00%)  0/201 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Dyspnoea  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Surgical and medical procedures       
Colostomy closure  1  0/308 (0.00%)  0/313 (0.00%)  1/309 (0.32%) 
Rehabilitation therapy  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  0/308 (0.00%)  0/313 (0.00%)  2/309 (0.65%) 
Hypotension  1  1/308 (0.32%)  1/313 (0.32%)  0/309 (0.00%) 
Peripheral artery thrombosis  1  0/308 (0.00%)  1/313 (0.32%)  0/309 (0.00%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Idalopirdine 30 mg Idalopirdine 60 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   39/308 (12.66%)   56/313 (17.89%)   49/309 (15.86%) 
Injury, poisoning and procedural complications       
Accidental overdose  1  27/308 (8.77%)  27/313 (8.63%)  16/309 (5.18%) 
Fall  1  15/308 (4.87%)  16/313 (5.11%)  19/309 (6.15%) 
Investigations       
Gamma-glutamyltransferase increased  1  1/308 (0.32%)  17/313 (5.43%)  15/309 (4.85%) 
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
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Name/Title: Email contact via
Organization: H. Lundbeck A/S
Phone: +4536301311
EMail: LundbeckClinicalTrials@lundbeck.com
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Responsible Party: H. Lundbeck A/S
ClinicalTrials.gov Identifier: NCT01955161    
Other Study ID Numbers: 14861A
2012-004763-45 ( EudraCT Number )
First Submitted: September 27, 2013
First Posted: October 7, 2013
Results First Submitted: July 11, 2017
Results First Posted: September 19, 2017
Last Update Posted: September 19, 2017