Study of Idalopirdine in Patients With Mild - Moderate Alzheimer's Disease Treated With Donepezil
- Registration Number
- NCT01955161
- Lead Sponsor
- H. Lundbeck A/S
- 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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 933
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo adjunct to 10 mg Donepezil Idalopirdine 30 mg Idalopirdine Idalopirdine adjunct to 10 mg Donepezil Idalopirdine 60 mg Idalopirdine Idalopirdine adjunct to 10 mg Donepezil
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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).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).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).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.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.Clinical Improvement Week 24 Clinical response at Week 24 (based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes \[change in ADAS-cog below or equal to -4, change in ADCS-ADL23 at least 0, and ADCS-CGIC below or equal to 4\])
Clinical Worsening Week 24 Clinical worsening at Week 24 (Based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes \[change in ADAS-cog above or equal to 4, change in ADCS-ADL23 below 0, and ADCS-CGIC above 4\])
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).
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.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).
Trial Locations
- Locations (137)
US043
🇺🇸Staten Island, New York, United States
US002
🇺🇸Los Angeles, California, United States
US042
🇺🇸Boca Raton, Florida, United States
US035
🇺🇸Kalamazoo, Michigan, United States
US038
🇺🇸Port Charlotte, Florida, United States
US001
🇺🇸West Palm Beach, Florida, United States
US046
🇺🇸Princeton, New Jersey, United States
US018
🇺🇸Santa Ana, California, United States
US006
🇺🇸Columbus, Ohio, United States
US024
🇺🇸Little Rock, Arkansas, United States
US052
🇺🇸Edmond, Oklahoma, United States
US045
🇺🇸Long Beach, California, United States
US029
🇺🇸New York, New York, United States
US056
🇺🇸New York, New York, United States
IT006
🇮🇹Brescia, Italy
IT005
🇮🇹Genoa, Italy
CL004
🇨🇱Antofagasta, Chile
CL003
🇨🇱Santiago, Chile
DE010
🇩🇪Günzburg, Germany
IT004
🇮🇹Ancona, Italy
FR005
🇫🇷Paris cedex 10, France
DE009
🇩🇪Munchen, Germany
CZ006
🇨🇿Brno, Czechia
DE004
🇩🇪Unterhaching, Germany
DE002
🇩🇪Berlin, Germany
FR002
🇫🇷Toulouse, France
DE006
🇩🇪Ellwangen, Germany
US041
🇺🇸Flowood, Mississippi, United States
IT002
🇮🇹Firenze, Italy
CA008
🇨🇦Newmarket, Canada
CA001
🇨🇦Toronto, Canada
CZ003
🇨🇿Praha 10, Czechia
CZ002
🇨🇿Praha 6, Czechia
FR004
🇫🇷Saint Etienne Cedex 2, France
FR003
🇫🇷Nantes Cedex, France
CZ005
🇨🇿Rychnov nad Kneznou, Czechia
CZ004
🇨🇿Pardubice, Czechia
CZ007
🇨🇿Kutna Hora, Czechia
CZ001
🇨🇿Praha 2, Czechia
FR001
🇫🇷Paris, France
FR006
🇫🇷Besancon Cedex, France
ZA004
🇿🇦George, South Africa
ES006
🇪🇸Barcelona, Spain
FR008
🇫🇷Limoges Cedex1, France
ZA002
🇿🇦Rosebank, South Africa
DE005
🇩🇪Hannover, Germany
PL004
🇵🇱Gliwice, Poland
PL003
🇵🇱Warszawa, Poland
UA008
🇺🇦Dnipropetrovsk, Ukraine
ES005
🇪🇸Manresa, Spain
UA006
🇺🇦Kherson,Vil. Stepanivka, Ukraine
UA007
🇺🇦Kyiv, Ukraine
UA001
🇺🇦Lviv, Ukraine
PL007
🇵🇱Katowice, Poland
ES003
🇪🇸Santiago de Compostela, Spain
US012
🇺🇸Phoenix, Arizona, United States
US058
🇺🇸San Francisco, California, United States
US040
🇺🇸Indianapolis, Indiana, United States
US027
🇺🇸Birmingham, Alabama, United States
DK003
🇩🇰Aarhus N, Denmark
DK001
🇩🇰Copenhagen, Denmark
DK002
🇩🇰Odense C, Denmark
US060
🇺🇸Denver, Colorado, United States
US026
🇺🇸Portland, Oregon, United States
CL001
🇨🇱Valdivia, Chile
CL002
🇨🇱Santiago, Chile
RO001
🇷🇴Tirgu Mures, Romania
BG005
🇧🇬Plovdiv, Bulgaria
BG002
🇧🇬Sofia, Bulgaria
CA002
🇨🇦Gatineau, Canada
US023
🇺🇸Imperial, California, United States
US053
🇺🇸Glendale, California, United States
US015
🇺🇸La Jolla, California, United States
US021
🇺🇸Bradenton, Florida, United States
US020
🇺🇸Atlanta, Georgia, United States
US051
🇺🇸Joliet, Illinois, United States
US030
🇺🇸Chicago, Illinois, United States
US048
🇺🇸Kailua, Hawaii, United States
US036
🇺🇸Freeport, Maine, United States
US032
🇺🇸Newton, Massachusetts, United States
US049
🇺🇸Albany, New York, United States
US044
🇺🇸Toms River, New Jersey, United States
US054
🇺🇸Saint Louis, Missouri, United States
US028
🇺🇸Toms River, New Jersey, United States
US010
🇺🇸Amherst, New York, United States
US008
🇺🇸New York, New York, United States
US014
🇺🇸Manhasset, New York, United States
AR003
🇦🇷Buenos Aires, Argentina
US037
🇺🇸Orangeburg, New York, United States
US007
🇺🇸Centerville, Ohio, United States
US057
🇺🇸Jenkintown, Pennsylvania, United States
US025
🇺🇸Madison, Wisconsin, United States
US047
🇺🇸Arlington, Virginia, United States
AR002
🇦🇷Buenos Aires, Argentina
AR006
🇦🇷Buenos Aires, Argentina
AR007
🇦🇷Buenos Aires, Argentina
AR010
🇦🇷Rosario, Argentina
BE003
🇧🇪Brugge, Belgium
AR009
🇦🇷Cordoba, Argentina
AR004
🇦🇷Mar del Plata, Argentina
AR005
🇦🇷Mendoza, Argentina
BE002
🇧🇪Brussels, Belgium
AR008
🇦🇷Mendoza, Argentina
BE006
🇧🇪Thuin, Belgium
BE005
🇧🇪Leuven, Belgium
BE004
🇧🇪Bruxelles, Belgium
BE001
🇧🇪Roeselare, Belgium
BG001
🇧🇬Sofia, Bulgaria
BG006
🇧🇬Sofia, Bulgaria
BG003
🇧🇬Sofia, Bulgaria
BG004
🇧🇬Sofia, Bulgaria
BG007
🇧🇬Varna, Bulgaria
CA006
🇨🇦London, Canada
CA004
🇨🇦Toronto, Canada
CL005
🇨🇱Santiago, Chile
ZA003
🇿🇦Bloemfontein, South Africa
DE007
🇩🇪Heidelberg, Germany
DE008
🇩🇪Ulm, Germany
PL006
🇵🇱Sopot, Poland
IT003
🇮🇹Lamezia Terme, Italy
PL005
🇵🇱Poznan, Poland
IT001
🇮🇹Milano, Italy
PL008
🇵🇱Wroclaw, Poland
IT007
🇮🇹Palermo, Italy
RO002
🇷🇴Bucharest, Romania
PL002
🇵🇱Szczecin, Poland
ZA006
🇿🇦Cape Town, South Africa
ES002
🇪🇸Alicante, Spain
ZA007
🇿🇦Cape Town, South Africa
ZA001
🇿🇦Pretoria, South Africa
ES001
🇪🇸San Sebastian, Spain
ZA005
🇿🇦Port Elizabeth, South Africa
ES004
🇪🇸Salamanca, Spain
US050
🇺🇸Brooksville, Florida, United States
US019
🇺🇸Orlando, Florida, United States
US004
🇺🇸Milwaukee, Wisconsin, United States
UA005
🇺🇦Kyiv, Ukraine