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

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01955161
• Collaborator: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Enrollment: 933
• Locations: 137
• Arms: 3
• Duration (Months): 33
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To establish efficacy of idalopirdine as adjunctive therapy to donepezil for symptomatic treatment of patients with mild-to-moderate Alzheimer's disease (AD).

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Placebo; Drug: Idalopirdine	Phase 3

Detailed Description

The study consisted of a screening period (up to 2-week period from screening to randomization), a 24-week double-blind treatment period with placebo or idalopirdine 30 mg/day or 60 mg/day as adjunctive therapy to donepezil 10 mg/day, and a 4-week safety follow-up period following study completion or withdrawal from treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 933 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomised, Double-blind, Parallel-group, Placebo-controlled, Fixed-dose Study of Idalopirdine in Patients With Mild - Moderate Alzheimer's Disease Treated With Donepezil
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Jul 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Placebo adjunct to 10 mg Donepezil	Drug: Placebo; Once daily, matching placebo capsules, orally
Experimental: Idalopirdine 30 mg Idalopirdine adjunct to 10 mg Donepezil	Drug: Idalopirdine; Once daily, encapsulated tablets, orally
Experimental: Idalopirdine 60 mg Idalopirdine adjunct to 10 mg Donepezil	Drug: Idalopirdine; Once daily, encapsulated tablets, orally

Outcome Measures

Primary Outcome Measures

1. Change in Cognition [Baseline to Week 24]

   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).

Secondary Outcome Measures

1. Change in Daily Functioning [Baseline to Week 24]

   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).

2. Change in Global Impression [Baseline to Week 24]

   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).

3. Change in Behavioural Disturbance [Baseline to Week 24]

   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).

4. Change in Individual Behavioural Disturbance Items [Baseline to Week 24]

   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.

5. Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline [Baseline to Week 24]

   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.

6. Clinical Improvement [Week 24]

   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])

7. Clinical Worsening [Week 24]

   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])

8. Change in Cognitive Aspects of Mental Function [Baseline to Week 24]

   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).

9. Change in Health-related Quality of Life (EQ-5D) Utility Score [Baseline to Week 24]

   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.

10. Change in Health-related Quality of Life (EQ-5D VAS) [Baseline to Week 24]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The patient has a knowledgeable and reliable caregiver.

• The patient is an outpatient.

• The patient has probable AD.

• The patient has mild to moderate AD.

• Stable treatment with donepezil.

• The patient, if a woman, must have had her last natural menstruation ≥24 months prior to baseline, OR be surgically sterile.

• The patient, if a man, agrees to protocol-defined use of effective contraception if his female partner is of childbearing potential, OR must have been surgically sterilised prior to the screening visit.

Exclusion Criteria:

• The patient has evidence of any clinically significant neurodegenerative disease, or other serious neurological disorders other than AD.

• The patient has a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) Axis I disorder other than AD.

• The patient has evidence of clinically significant disease.

• The patient's donepezil therapy is likely to be interrupted or discontinued during the study.

• The patient is currently receiving memantine or has taken memantine within 2 months prior to screening.

Other inclusion and exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	US027	Birmingham	Alabama	United States
2	US012	Phoenix	Arizona	United States
3	US024	Little Rock	Arkansas	United States
4	US053	Glendale	California	United States
5	US023	Imperial	California	United States
6	US015	La Jolla	California	United States
7	US045	Long Beach	California	United States
8	US002	Los Angeles	California	United States
9	US058	San Francisco	California	United States
10	US018	Santa Ana	California	United States
11	US060	Denver	Colorado	United States
12	US042	Boca Raton	Florida	United States
13	US021	Bradenton	Florida	United States
14	US050	Brooksville	Florida	United States
15	US019	Orlando	Florida	United States
16	US038	Port Charlotte	Florida	United States
17	US001	West Palm Beach	Florida	United States
18	US020	Atlanta	Georgia	United States
19	US048	Kailua	Hawaii	United States
20	US030	Chicago	Illinois	United States
21	US051	Joliet	Illinois	United States
22	US040	Indianapolis	Indiana	United States
23	US036	Freeport	Maine	United States
24	US032	Newton	Massachusetts	United States
25	US035	Kalamazoo	Michigan	United States
26	US041	Flowood	Mississippi	United States
27	US054	Saint Louis	Missouri	United States
28	US046	Princeton	New Jersey	United States
29	US028	Toms River	New Jersey	United States
30	US044	Toms River	New Jersey	United States
31	US049	Albany	New York	United States
32	US010	Amherst	New York	United States
33	US014	Manhasset	New York	United States
34	US008	New York	New York	United States
35	US029	New York	New York	United States
36	US056	New York	New York	United States
37	US037	Orangeburg	New York	United States
38	US043	Staten Island	New York	United States
39	US007	Centerville	Ohio	United States
40	US006	Columbus	Ohio	United States
41	US052	Edmond	Oklahoma	United States
42	US026	Portland	Oregon	United States
43	US057	Jenkintown	Pennsylvania	United States
44	US047	Arlington	Virginia	United States
45	US025	Madison	Wisconsin	United States
46	US004	Milwaukee	Wisconsin	United States
47	AR002	Buenos Aires		Argentina
48	AR003	Buenos Aires		Argentina
49	AR006	Buenos Aires		Argentina
50	AR007	Buenos Aires		Argentina
51	AR009	Cordoba		Argentina
52	AR004	Mar del Plata		Argentina
53	AR005	Mendoza		Argentina
54	AR008	Mendoza		Argentina
55	AR010	Rosario		Argentina
56	BE003	Brugge		Belgium
57	BE002	Brussels		Belgium
58	BE004	Bruxelles		Belgium
59	BE005	Leuven		Belgium
60	BE001	Roeselare		Belgium
61	BE006	Thuin		Belgium
62	BG005	Plovdiv		Bulgaria
63	BG001	Sofia		Bulgaria
64	BG002	Sofia		Bulgaria
65	BG003	Sofia		Bulgaria
66	BG004	Sofia		Bulgaria
67	BG006	Sofia		Bulgaria
68	BG007	Varna		Bulgaria
69	CA002	Gatineau		Canada
70	CA006	London		Canada
71	CA008	Newmarket		Canada
72	CA001	Toronto		Canada
73	CA004	Toronto		Canada
74	CL004	Antofagasta		Chile
75	CL002	Santiago		Chile
76	CL003	Santiago		Chile
77	CL005	Santiago		Chile
78	CL001	Valdivia		Chile
79	CZ006	Brno		Czechia
80	CZ007	Kutna Hora		Czechia
81	CZ004	Pardubice		Czechia
82	CZ003	Praha 10		Czechia
83	CZ001	Praha 2		Czechia
84	CZ002	Praha 6		Czechia
85	CZ005	Rychnov nad Kneznou		Czechia
86	DK003	Aarhus N		Denmark
87	DK001	Copenhagen		Denmark
88	DK002	Odense C		Denmark
89	FR006	Besancon Cedex		France
90	FR008	Limoges Cedex1		France
91	FR003	Nantes Cedex		France
92	FR005	Paris cedex 10		France
93	FR001	Paris		France
94	FR004	Saint Etienne Cedex 2		France
95	FR002	Toulouse		France
96	DE002	Berlin		Germany
97	DE006	Ellwangen		Germany
98	DE010	Günzburg		Germany
99	DE005	Hannover		Germany
100	DE007	Heidelberg		Germany
101	DE009	Munchen		Germany
102	DE008	Ulm		Germany
103	DE004	Unterhaching		Germany
104	IT004	Ancona		Italy
105	IT006	Brescia		Italy
106	IT002	Firenze		Italy
107	IT005	Genoa		Italy
108	IT003	Lamezia Terme		Italy
109	IT001	Milano		Italy
110	IT007	Palermo		Italy
111	PL004	Gliwice		Poland
112	PL007	Katowice		Poland
113	PL005	Poznan		Poland
114	PL006	Sopot		Poland
115	PL002	Szczecin		Poland
116	PL003	Warszawa		Poland
117	PL008	Wroclaw		Poland
118	RO002	Bucharest		Romania
119	RO001	Tirgu Mures		Romania
120	ZA003	Bloemfontein		South Africa
121	ZA006	Cape Town		South Africa
122	ZA007	Cape Town		South Africa
123	ZA004	George		South Africa
124	ZA005	Port Elizabeth		South Africa
125	ZA001	Pretoria		South Africa
126	ZA002	Rosebank		South Africa
127	ES002	Alicante		Spain
128	ES006	Barcelona		Spain
129	ES005	Manresa		Spain
130	ES004	Salamanca		Spain
131	ES001	San Sebastian		Spain
132	ES003	Santiago de Compostela		Spain
133	UA008	Dnipropetrovsk		Ukraine
134	UA006	Kherson,Vil. Stepanivka		Ukraine
135	UA005	Kyiv		Ukraine
136	UA007	Kyiv		Ukraine
137	UA001	Lviv		Ukraine

Sponsors and Collaborators

• H. Lundbeck A/S
• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Email contact via H. Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT01955161
• Other Study ID Numbers: 14861A; 2012-004763-45
• First Posted: Oct 7, 2013
• Last Update Posted: Sep 19, 2017
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Arm/Group Title	Placebo	Idalopirdine 30 mg	Idalopirdine 60 mg
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

Baseline Characteristics

Arm/Group Title	Placebo	Idalopirdine 30 mg	Idalopirdine 60 mg	Total
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 Participants	308	313	309	930
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.8 (8.0)	74.0 (8.8)	73.7 (8.6)	73.8 (8.5)
Sex: Female, Male (Count of Participants)
Female	198 64.3%	208 66.5%	201 65%	607 65.3%
Male	110 35.7%	105 33.5%	108 35%	323 34.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 0.6%	1 0.3%	1 0.3%	4 0.4%
Not Hispanic or Latino	40 13%	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) (Count of Participants)
American Indian or Alaska Native	NA NaN	NA NaN	NA NaN	NA NaN
Asian	1 0.3%	1 0.3%	3 1%	5 0.5%
Native Hawaiian or Other Pacific Islander	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 NaN	NA NaN	NA NaN	NA NaN
Unknown or Not Reported	22 7.1%	19 6.1%	19 6.1%	60 6.5%
Region of Enrollment (participants) [Number]
Argentina	24 7.8%	25 8%	21 6.8%	70 7.5%
Romania	4 1.3%	2 0.6%	4 1.3%	10 1.1%
Czech Republic	36 11.7%	35 11.2%	38 12.3%	109 11.7%
United States	42 13.6%	45 14.4%	43 13.9%	130 14%
Ukraine	21 6.8%	20 6.4%	20 6.5%	61 6.6%
Spain	19 6.2%	22 7%	19 6.1%	60 6.5%
Canada	15 4.9%	12 3.8%	13 4.2%	40 4.3%
Belgium	6 1.9%	7 2.2%	5 1.6%	18 1.9%
Denmark	4 1.3%	4 1.3%	5 1.6%	13 1.4%
Poland	25 8.1%	24 7.7%	24 7.8%	73 7.8%
Italy	13 4.2%	12 3.8%	11 3.6%	36 3.9%
South Africa	18 5.8%	19 6.1%	20 6.5%	57 6.1%
Bulgaria	22 7.1%	19 6.1%	19 6.1%	60 6.5%
Chile	28 9.1%	30 9.6%	31 10%	89 9.6%
France	14 4.5%	15 4.8%	17 5.5%	46 4.9%
Germany	17 5.5%	22 7%	19 6.1%	58 6.2%
MMSE total score at screening (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	17.4 (2.9)	17.2 (3.1)	17.4 (2.9)	17.4 (3.0)

Outcome Measures

1. Primary Outcome

Title	Change in Cognition
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

Outcome Measure Data

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
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
Measure Participants	304	310	308
Least Squares Mean (Standard Error) [units on a scale]	0.13 (0.35)	0.47 (0.35)	0.18 (0.35)

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
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

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
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
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

Outcome Measure Data

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
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
Measure Participants	304	310	308
Least Squares Mean (Standard Error) [units on a scale]	-2.03 (0.49)	-2.12 (0.48)	-2.02 (0.49)

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
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.

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
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
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

Outcome Measure Data

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
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
Measure Participants	303	309	307
Least Squares Mean (Standard Error) [units on a scale]	4.29 (0.07)	4.32 (0.07)	4.13 (0.07)

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
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.

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
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
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

Outcome Measure Data

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
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
Measure Participants	304	310	308
Least Squares Mean (Standard Error) [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
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

Outcome Measure Data

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
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
Measure Participants	304	310	308
Delusions	-0.11 (0.09)	-0.04 (0.09)	-0.01 (0.09)
Hallucinations	0.13 (0.07)	0.03 (0.07)	-0.03 (0.07)
Agitation/aggression	0.01 (0.11)	0.04 (0.11)	0.10 (0.11)
Depression/dysphoria	0.02 (0.09)	-0.06 (0.09)	-0.08 (0.10)
Anxiety	-0.02 (0.11)	-0.13 (0.11)	-0.13 (0.11)
Elation/euphoria	0.09 (0.05)	0.03 (0.05)	0.03 (0.05)
Apathy/indifference	-0.18 (0.15)	-0.23 (0.15)	-0.27 (0.15)
Disinhibition	0.05 (0.08)	-0.06 (0.08)	-0.01 (0.08)
Irritability/lability	-0.14 (0.12)	0.02 (0.12)	0.00 (0.12)
Aberrant motor behaviour	0.03 (0.12)	0.33 (0.12)	-0.13 (0.13)
Sleep	0.03 (0.11)	0.01 (0.11)	0.03 (0.11)
Appetite/eating disorder	-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
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

Outcome Measure Data

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
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
Measure Participants	88	83	76
Least Squares Mean (Standard Error) [units on a scale]	-1.12 (0.30)	-1.56 (0.30)	-1.64 (0.32)

7. Secondary Outcome

Title	Clinical Improvement
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

Outcome Measure Data

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
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
Measure Participants	284	290	278
Count of Participants [Participants]	34 11%	37 11.8%	27 8.7%

8. Secondary Outcome

Title	Clinical Worsening
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

Outcome Measure Data

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
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
Measure Participants	284	290	278
Count of Participants [Participants]	40 13%	42 13.4%	33 10.7%

9. Secondary Outcome

Title	Change in Cognitive Aspects of Mental Function
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

Outcome Measure Data

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
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
Measure Participants	282	288	274
Least Squares Mean (Standard Error) [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
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 to Week 24

Outcome Measure Data

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
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
Measure Participants	301	306	304
Least Squares Mean (Standard Error) [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)
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

Outcome Measure Data

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
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
Measure Participants	301	307	304
Least Squares Mean (Standard Error) [units on a scale]	-0.40 (1.01)	-0.12 (1.01)	0.34 (1.03)

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/308 (0.3%)		1/313 (0.3%)		3/309 (1%)
Serious Adverse Events
	Placebo		Idalopirdine 30 mg		Idalopirdine 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/308 (3.9%)		18/313 (5.8%)		20/309 (6.5%)
Blood and lymphatic system disorders
Anaemia	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Cardiac disorders
Acute myocardial infarction	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Angina pectoris	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Atrial fibrillation	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Bradycardia	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Coronary artery disease	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Myocardial infarction	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Sinus node dysfunction	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Gastrointestinal disorders
Gastrooesophageal reflux disease	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Pancreatitis acute	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
General disorders
Sudden death	0/308 (0%)		1/313 (0.3%)		1/309 (0.3%)
Infections and infestations
Appendicitis	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Bacterial diarrhoea	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Bacterial sepsis	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Gastroenteritis viral	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Influenza	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Pneumonia	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Pneumonia bacterial	2/308 (0.6%)		0/313 (0%)		0/309 (0%)
Respiratory tract infection	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Urinary tract infection	0/308 (0%)		1/313 (0.3%)		1/309 (0.3%)
Urinary tract infection bacterial	1/308 (0.3%)		1/313 (0.3%)		0/309 (0%)
Injury, poisoning and procedural complications
Femoral neck fracture	1/308 (0.3%)		0/313 (0%)		1/309 (0.3%)
Head injury	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Hip fracture	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Radius fracture	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Wrist fracture	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Investigations
Alanine aminotransferase increased	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Aspartate aminotransferase increased	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Bilirubin conjugated increased	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Blood alkaline phosphatase increased	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Blood bilirubin increased	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
C-reactive protein increased	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Gamma-glutamyltransferase increased	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Musculoskeletal and connective tissue disorders
Spinal pain	2/308 (0.6%)		0/313 (0%)		0/309 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Metastases to peritoneum	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Nervous system disorders
Cerebral arteriosclerosis	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Cerebral haematoma	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Cerebral ischaemia	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Dementia alzheimer's type	1/308 (0.3%)		0/313 (0%)		0/309 (0%)
Presyncope	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Syncope	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Transient ischaemic attack	1/308 (0.3%)		1/313 (0.3%)		1/309 (0.3%)
Psychiatric disorders
Confusional state	1/308 (0.3%)		0/313 (0%)		1/309 (0.3%)
Delirium	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Impulse-control disorder	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Renal and urinary disorders
Calculus bladder	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Reproductive system and breast disorders
Metrorrhagia	0/198 (0%)		0/208 (0%)		1/201 (0.5%)
Vaginal fistula	1/198 (0.5%)		0/208 (0%)		0/201 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Dyspnoea	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Surgical and medical procedures
Colostomy closure	0/308 (0%)		0/313 (0%)		1/309 (0.3%)
Rehabilitation therapy	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Vascular disorders
Deep vein thrombosis	0/308 (0%)		0/313 (0%)		2/309 (0.6%)
Hypotension	1/308 (0.3%)		1/313 (0.3%)		0/309 (0%)
Peripheral artery thrombosis	0/308 (0%)		1/313 (0.3%)		0/309 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Idalopirdine 30 mg		Idalopirdine 60 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/308 (12.7%)		56/313 (17.9%)		49/309 (15.9%)
Injury, poisoning and procedural complications
Accidental overdose	27/308 (8.8%)		27/313 (8.6%)		16/309 (5.2%)
Fall	15/308 (4.9%)		16/313 (5.1%)		19/309 (6.1%)
Investigations
Gamma-glutamyltransferase increased	1/308 (0.3%)		17/313 (5.4%)		15/309 (4.9%)

Limitations/Caveats

[Not Specified]

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.