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

Alzheimer's Disease Clinical Trial

— STARSHINE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01955161
• Other study ID #: 14861A
• Secondary ID: 2012-004763-45
• Status: Completed
• Phase: Phase 3
• First received: September 27, 2013
• Last updated: August 22, 2017
• Start date: October 2013
• Est. completion date: July 2016

Study information

• Verified date: August 2017
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 933
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Placebo
Once daily, matching placebo capsules, orally
• Idalopirdine
Once daily, encapsulated tablets, orally

Locations

Country	Name	City	State
Argentina	AR002	Buenos Aires
Argentina	AR003	Buenos Aires
Argentina	AR006	Buenos Aires
Argentina	AR007	Buenos Aires
Argentina	AR009	Cordoba
Argentina	AR004	Mar del Plata
Argentina	AR005	Mendoza
Argentina	AR008	Mendoza
Argentina	AR010	Rosario
Belgium	BE003	Brugge
Belgium	BE002	Brussels
Belgium	BE004	Bruxelles
Belgium	BE005	Leuven
Belgium	BE001	Roeselare
Belgium	BE006	Thuin
Bulgaria	BG005	Plovdiv
Bulgaria	BG001	Sofia
Bulgaria	BG002	Sofia
Bulgaria	BG003	Sofia
Bulgaria	BG004	Sofia
Bulgaria	BG006	Sofia
Bulgaria	BG007	Varna
Canada	CA002	Gatineau
Canada	CA006	London
Canada	CA008	Newmarket
Canada	CA001	Toronto
Canada	CA004	Toronto
Chile	CL004	Antofagasta
Chile	CL002	Santiago
Chile	CL003	Santiago
Chile	CL005	Santiago
Chile	CL001	Valdivia
Czechia	CZ006	Brno
Czechia	CZ007	Kutna Hora
Czechia	CZ004	Pardubice
Czechia	CZ003	Praha 10
Czechia	CZ001	Praha 2
Czechia	CZ002	Praha 6
Czechia	CZ005	Rychnov nad Kneznou
Denmark	DK003	Aarhus N
Denmark	DK001	Copenhagen
Denmark	DK002	Odense C
France	FR006	Besancon Cedex
France	FR008	Limoges Cedex1
France	FR003	Nantes Cedex
France	FR001	Paris
France	FR005	Paris cedex 10
France	FR004	Saint Etienne Cedex 2
France	FR002	Toulouse
Germany	DE002	Berlin
Germany	DE006	Ellwangen
Germany	DE010	Günzburg
Germany	DE005	Hannover
Germany	DE007	Heidelberg
Germany	DE009	Munchen
Germany	DE008	Ulm
Germany	DE004	Unterhaching
Italy	IT004	Ancona
Italy	IT006	Brescia
Italy	IT002	Firenze
Italy	IT005	Genoa
Italy	IT003	Lamezia Terme
Italy	IT001	Milano
Italy	IT007	Palermo
Poland	PL004	Gliwice
Poland	PL007	Katowice
Poland	PL005	Poznan
Poland	PL006	Sopot
Poland	PL002	Szczecin
Poland	PL003	Warszawa
Poland	PL008	Wroclaw
Romania	RO002	Bucharest
Romania	RO001	Tirgu Mures
South Africa	ZA003	Bloemfontein
South Africa	ZA006	Cape Town
South Africa	ZA007	Cape Town
South Africa	ZA004	George
South Africa	ZA005	Port Elizabeth
South Africa	ZA001	Pretoria
South Africa	ZA002	Rosebank
Spain	ES002	Alicante
Spain	ES006	Barcelona
Spain	ES005	Manresa
Spain	ES004	Salamanca
Spain	ES001	San Sebastian
Spain	ES003	Santiago de Compostela
Ukraine	UA008	Dnipropetrovsk
Ukraine	UA006	Kherson,Vil. Stepanivka
Ukraine	UA005	Kyiv
Ukraine	UA007	Kyiv
Ukraine	UA001	Lviv
United States	US049	Albany	New York
United States	US010	Amherst	New York
United States	US047	Arlington	Virginia
United States	US020	Atlanta	Georgia
United States	US027	Birmingham	Alabama
United States	US042	Boca Raton	Florida
United States	US021	Bradenton	Florida
United States	US050	Brooksville	Florida
United States	US007	Centerville	Ohio
United States	US030	Chicago	Illinois
United States	US006	Columbus	Ohio
United States	US060	Denver	Colorado
United States	US052	Edmond	Oklahoma
United States	US041	Flowood	Mississippi
United States	US036	Freeport	Maine
United States	US053	Glendale	California
United States	US023	Imperial	California
United States	US040	Indianapolis	Indiana
United States	US057	Jenkintown	Pennsylvania
United States	US051	Joliet	Illinois
United States	US048	Kailua	Hawaii
United States	US035	Kalamazoo	Michigan
United States	US015	La Jolla	California
United States	US024	Little Rock	Arkansas
United States	US045	Long Beach	California
United States	US002	Los Angeles	California
United States	US025	Madison	Wisconsin
United States	US014	Manhasset	New York
United States	US004	Milwaukee	Wisconsin
United States	US008	New York	New York
United States	US029	New York	New York
United States	US056	New York	New York
United States	US032	Newton	Massachusetts
United States	US037	Orangeburg	New York
United States	US019	Orlando	Florida
United States	US012	Phoenix	Arizona
United States	US038	Port Charlotte	Florida
United States	US026	Portland	Oregon
United States	US046	Princeton	New Jersey
United States	US054	Saint Louis	Missouri
United States	US058	San Francisco	California
United States	US018	Santa Ana	California
United States	US043	Staten Island	New York
United States	US028	Toms River	New Jersey
United States	US044	Toms River	New Jersey
United States	US001	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lundbeck A/S	Otsuka Pharmaceutical Co., Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Bulgaria,  Canada,  Chile,  Czechia,  Denmark,  France,  Germany,  Italy,  Poland,  Romania,  South Africa,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cognition	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).	Baseline to Week 24
Secondary	Change in Daily Functioning	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).	Baseline to Week 24
Secondary	Change in Global Impression	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).	Baseline to Week 24
Secondary	Change in Behavioural Disturbance	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).	Baseline to Week 24
Secondary	Change in Individual Behavioural Disturbance Items	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.	Baseline to Week 24
Secondary	Change in NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline	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.	Baseline to Week 24
Secondary	Clinical Improvement	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])	Week 24
Secondary	Clinical Worsening	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])	Week 24
Secondary	Change in Cognitive Aspects of Mental Function	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).	Baseline to Week 24
Secondary	Change in Health-related Quality of Life (EQ-5D) Utility Score	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.	Baseline to Week 24
Secondary	Change in Health-related Quality of Life (EQ-5D VAS)	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).	Baseline to Week 24