Long-term Safety and Tolerability of Idalopirdine (Lu AE58054) as Adjunctive Treatment to Donepezil in Patients With Mild-moderate Alzheimer's Disease

Alzheimer's Disease Clinical Trial

— STAR Extension  

Official title:

An Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Idalopirdine (Lu AE58054) as Adjunctive Treatment to Donepezil in Patients With Mild-moderate Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02079246
• Other study ID #: 14861B
• Secondary ID: 2013-000001-23
• Status: Completed
• Phase: Phase 3
• Start date: April 7, 2014
• Est. completion date: July 6, 2017

Study information

• Verified date: August 2018
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the long-term safety and tolerability of idalopirdine (Lu AE58054) as adjunctive therapy to donepezil in patients with mild-moderate Alzheimer's Disease (AD).

Description:

This is an interventional, multi-national, multi-site, open-label extension study in patients with mild to moderate AD who completed the 24-week lead-in study 14861A (NCT01955161) or 14862A (NCT02006641).

Patients received 28-weeks of open-label treatment with idalopirdine 60 mg/day (option to reduce to 30 mg/day) as adjunctive treatment to donepezil. Approximately 100 patients, who had completed the initial 28-week period (OLEX), were included in a 24 week open-label treatment period with memantine (OLEX-MEM) that evaluated the safety and tolerability of concomitant memantine therapy in patients who were already on a stable treatment with idalopirdine and donepezil and for whom memantine treatment was clinically indicated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1463
• Est. completion date: July 6, 2017
• Est. primary completion date: July 6, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• the patient has completed Visit 7 (Completion Visit) in the lead-in double-blind, placebo controlled clinical studies 14861A/NCT01955161 or 14862A/NCT02006641

For patients in the OLEX-MEM:

• The patient has completed Visit 6 (Week 28) of the OLEX.

• The patient, according to the judgement of the investigator, requires initiation of treatment with memantine as per local label/SmPC/treatment guidelines.

Exclusion Criteria:

• The patient has a moderate or severe ongoing adverse event from the lead-in study considered a potential safety risk by the investigator.

• The patient has experienced seizures before Completion Visit in the lead-in study.

• The patient has evidence of clinically significant disease.

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

• The patient is receiving therapy with another acetylcholinesterase inhibitors (AChEI).

Other protocol-defined inclusion and exclusion criteria may apply.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Idalopirdine 60 mg
once daily, encapsulated tablets, orally

Locations

Country	Name	City	State
Argentina	AR303	Banfield
Argentina	AR007	Buenos Aires
Argentina	AR003	Ciudad Autonoma Buenos Aires
Argentina	AR304	Ciudad Autonoma Buenos Aires
Argentina	AR308	Ciudad Autonoma Buenos Aires
Argentina	AR311	Ciudad Autonoma Buenos Aires
Argentina	AR313	Ciudad Autonoma Buenos Aires
Argentina	AR314	Ciudad Autonoma Buenos Aires
Argentina	AR312	Ciudad Autonoma de Buenos Aires
Argentina	AR009	Cordoba
Argentina	AR307	Cordoba
Argentina	AR309	Cordoba
Argentina	AR305	Godoy Cruz
Argentina	AR004	Mar del Plata
Argentina	AR005	Mendoza
Argentina	AR008	Mendoza
Argentina	AR310	Mendoza
Argentina	AR010	Rosario
Argentina	AR302	Santa Fe
Argentina	AR306	Santiago del Estero
Belgium	BE003	Brugge
Belgium	BE002	Brussels
Belgium	BE004	Bruxelles
Belgium	BE005	Leuven
Belgium	BE001	Roeselare
Brazil	BR307	Curitiba
Brazil	BR309	Curitiba
Brazil	BR303	Porto Alegre
Brazil	BR301	Rio de Janeiro
Brazil	BR306	Rio de Janeiro
Brazil	BR302	Sao Paulo
Brazil	BR304	São Paulo
Brazil	BR308	São Paulo
Bulgaria	BG005	Plovdiv
Bulgaria	BG001	Sofia
Bulgaria	BG002	Sofia
Bulgaria	BG003	Sofia
Bulgaria	BG004	Sofia
Bulgaria	BG006	Sofia
Canada	CA002	Gatineau
Canada	CA309	Gatineau
Canada	CA301	Halifax
Canada	CA302	Kelowna
Canada	CA006	London
Canada	CA306	Montreal
Canada	CA008	Newmarket
Canada	CA304	Qubec
Canada	CA001	Toronto
Canada	CA305	Toronto
Canada	CA308	Toronto
Canada	CA307	Verdun
Chile	CL004	Antofagasta
Chile	CL002	Santiago
Chile	CL003	Santiago
Chile	CL005	Santiago
Chile	CL001	Valdivia
Croatia	HR304	Zabok
Croatia	HR301	Zagreb
Croatia	HR302	Zagreb
Czechia	CZ006	Brno
Czechia	CZ309	Chocen
Czechia	CZ306	Hradec Kralove
Czechia	CZ007	Kutna Hora
Czechia	CZ004	Pardubice
Czechia	CZ003	Praha 10
Czechia	CZ304	Praha 10
Czechia	CZ310	Praha 10 - Strasnice
Czechia	CZ001	Praha 2
Czechia	CZ002	Praha 6
Czechia	CZ301	Praha 6
Czechia	CZ303	Praha 6
Czechia	CZ005	Rychnov nad Kneznou
Denmark	DK003	Aarhus N
Denmark	DK001	Copenhagen
Estonia	EE303	Tallin
Estonia	EE301	Tallinn
Estonia	EE302	Tartu
Finland	FI302	Kuopio
Finland	FI303	Oulu
Finland	FI301	Turku
France	FR006	Besancon Cedex
France	FR301	Bordeaux
France	FR308	Bron cedex
France	FR309	Elancourt
France	FR008	Limoges
France	FR302	Marseille cedex 5
France	FR312	Nantes
France	FR003	Nantes Cedex
France	FR303	Nice
France	FR001	Paris
France	FR311	Paris
France	FR005	Paris cedex 10
France	FR306	Reims
France	FR305	Rouen
France	FR004	Saint Priest en Jarez
France	FR313	Saint Priest en Jarez
France	FR002	Toulouse
Germany	DE002	Berlin
Germany	DE006	Ellwangen
Germany	DE005	Hannover
Germany	DE007	Heidelberg
Germany	DE009	Munchen
Germany	DE008	Ulm
Germany	DE004	Unterhaching
Hungary	HU304	Budapest
Hungary	HU305	Budapest
Hungary	HU301	Esztergom
Hungary	HU302	Szeged
Israel	IL302	Haifa
Israel	IL303	Holon
Israel	IL304	Ramat Gan
Italy	IT004	Ancona
Italy	IT006	Brescia
Italy	IT306	Brescia
Italy	IT309	Brescia
Italy	IT313	Cefalù
Italy	IT002	Firenze
Italy	IT311	Genova
Italy	IT003	Lamezia Terme
Italy	IT001	Milano
Italy	IT312	Monza
Italy	IT005	Palermo
Italy	IT007	Palermo
Italy	IT307	Perugia
Italy	IT301	Pisa
Italy	IT305	Roma
Italy	IT308	Roma
Italy	IT304	Torino
Italy	IT310	Torrette
Korea, Republic of	KR303	Busan
Korea, Republic of	KR301	Incheon
Korea, Republic of	KR308	Seongnam-si
Korea, Republic of	KR302	Seoul
Korea, Republic of	KR304	Seoul
Korea, Republic of	KR305	Seoul
Korea, Republic of	KR306	Seoul
Korea, Republic of	KR307	Seoul
Korea, Republic of	KR309	Seoul
Lithuania	LT302	Kaunas
Lithuania	LT303	Kaunas
Lithuania	LT301	Vilnius
Lithuania	LT304	Vilnius
Poland	PL301	Bialystok
Poland	PL304	Bydgoszcz
Poland	PL308	Gdynia
Poland	PL004	Gliwice
Poland	PL007	Katowice
Poland	PL309	Krakow
Poland	PL302	Lodz
Poland	PL310	Lubin
Poland	PL306	Lublin
Poland	PL307	Oswiecim
Poland	PL005	Pozna
Poland	PL303	Poznan
Poland	PL006	Sopot
Poland	PL002	Szczecin
Poland	PL311	Szczecin
Poland	PL003	Warszawa
Poland	PL008	Wroclaw
Portugal	PT301	Amadora
Portugal	PT302	Coimbra
Romania	RO002	Bucharest
Romania	RO001	Târgu-Mures
South Africa	ZA003	Bloemfontein
South Africa	ZA006	Cape Town
South Africa	ZA007	Cape Town
South Africa	ZA004	George
South Africa	ZA001	Pretoria
South Africa	ZA002	Rosebank
Spain	ES006	Barcelona
Spain	ES005	Manresa
Spain	ES004	Salamanca
Spain	ES001	San Sebastian
Spain	ES002	San Vicente del Raspeig
Spain	ES003	Santiago de Compostela
Taiwan	TW301	Kaohsiung
Taiwan	TW302	Kaohsiung
Taiwan	TW303	Tainan
Ukraine	UA008	Dnipropetrovsk
Ukraine	UA006	Kherson
Ukraine	UA005	Kyiv
Ukraine	UA007	Kyiv
Ukraine	UA001	Lviv
United Kingdom	GB307	Amersham
United Kingdom	GB301	Glasgow
United Kingdom	GB303	London
United Kingdom	GB308	London
United Kingdom	GB310	London
United Kingdom	GB306	Plymouth
United Kingdom	GB311	Plymouth
United Kingdom	GB309	Prescot
United Kingdom	GB305	Preston
United Kingdom	GB304	Southampton
United Kingdom	GB302	Swindon
United States	US047	Arlington	Virginia
United States	US304	Atlanta	Georgia
United States	US360	Augusta	Georgia
United States	US027	Birmingham	Alabama
United States	US344	Boston	Massachusetts
United States	US021	Bradenton	Florida
United States	US050	Brooksville	Florida
United States	US351	Carlsbad	California
United States	US007	Centerville	Ohio
United States	US316	Charlotte	North Carolina
United States	US030	Chicago	Illinois
United States	US323	Cincinnati	Ohio
United States	US006	Columbus	Ohio
United States	US306	Columbus	Ohio
United States	US356	Cordova	Tennessee
United States	US346	Costa Mesa	California
United States	US308	Delray Beach	Florida
United States	US041	Flowood	Mississippi
United States	US343	Fort Worth	Texas
United States	US036	Freeport	Maine
United States	US327	Fullerton	California
United States	US320	Hallandale Beach	Florida
United States	US321	Hattiesburg	Mississippi
United States	US347	Hialeah	Florida
United States	US354	Houston	Texas
United States	US023	Imperial	California
United States	US040	Indianapolis	Indiana
United States	US057	Jenkintown	Pennsylvania
United States	US048	Kailua	Hawaii
United States	US035	Kalamazoo	Michigan
United States	US334	Lake Charles	Louisiana
United States	US340	Lake Worth	Florida
United States	US352	Lakewood	Ohio
United States	US024	Little Rock	Arkansas
United States	US045	Long Beach	California
United States	US025	Madison	Wisconsin
United States	US339	Manchester	New Jersey
United States	US014	Manhasset	New York
United States	US303	Miami	Florida
United States	US313	Miami	Florida
United States	US004	Milwaukee	Wisconsin
United States	US029	New York	New York
United States	US333	Oklahoma City	Oklahoma
United States	US345	Orange City	Florida
United States	US019	Orlando	Florida
United States	US309	Palm Beach Gardens	Florida
United States	US012	Phoenix	Arizona
United States	US338	Phoenix	Arizona
United States	US324	Pittsburgh	Pennsylvania
United States	US341	Pittsburgh	Pennsylvania
United States	US038	Port Charlotte	Florida
United States	US319	Port Royal	South Carolina
United States	US026	Portland	Oregon
United States	US046	Princeton	New Jersey
United States	US307	Redlands	California
United States	US310	Saint Paul	Minnesota
United States	US058	San Francisco	California
United States	US018	Santa Ana	California
United States	US301	Santa Rosa	California
United States	US312	Staten Island	New York
United States	US302	Sunrise	Florida
United States	US028	Toms River	New Jersey
United States	US044	Toms River	New Jersey
United States	US336	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Croatia,  Czechia,  Denmark,  Estonia,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Lithuania,  Poland,  Portugal,  Romania,  South Africa,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Treatment Emergent Adverse Events (TEAEs) in the OLEX	A TEAE is an adverse event that starts or increases in intensity after the date of Baseline II.	Baseline II (start of OLEX, week 0) to end of OLEX (week 28)
Primary	Number of TEAEs in the OLEX-MEM	A TEAE is an adverse event that starts or increases in intensity after the date of Baseline III (start of OLEX-MEM).	From Baseline III (start of OLEX-MEM, Week 28) to end of OLEX-MEM (Week 52)
Secondary	Change in Cognition	Change from Baseline II to Week 28 in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) total score. The 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 II (start of OLEX, Week 0) to Week 28
Secondary	Clinical Global Impression Score	Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) score at Week 28. The ADCS-CGIC 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).	Week 28
Secondary	Change in Daily Functioning	Change from Baseline II to Week 28 in Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL23) total score. The 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 II (start of OLEX, Week 0) to Week 28
Secondary	Change in Behavioural Disturbance	Change from Baseline II to Week 28 in Neuropsychiatric Inventory (NPI) total score. The NPI 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 II (start of OLEX, Week 0) to Week 28
Secondary	Change in Cognitive Aspects of Mental Function	Change from Baseline II to Week 28 in Mini Mental State Examination (MMSE). The 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 II (start of OLEX, Week 0) to Week 28
Secondary	Change in Cognitive Aspects of Mental Function	Change from Baseline III to Week 52 in Mini Mental State Examination (MMSE). The 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 III (start of OLEX-MEM, Week 28) to Week 52