Study of Idalopirdine in Patients With Mild - Moderate Alzheimer's Disease Treated With an Acetylcholinesterase Inhibitor
- Registration Number
- NCT02006654
- Lead Sponsor
- H. Lundbeck A/S
- Brief Summary
To establish efficacy of idalopirdine as adjunctive therapy to acetylcholinesterase inhibitors (AChEIs) for symptomatic treatment of patients with mild-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 60mg/day as adjunctive therapy to an acetylcholinesterase inhibitor (donepezil 10mg/day, rivastigmine at the patient's individual maintenance dose, or galantamine at the patient's individual maintenance dose), and a 4-week safety follow-up period following study completion or withdrawal from treatment. The dose could be decreased once during the study to 30mg/day if 60mg/day was not well tolerated in the opinion of the investigator. The dose could be increased again to 60mg/day, after which the dose was kept fixed for the remainder of the study. Dose changes were permitted until Week 12 (Visit 5).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 734
- 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 an AChEI.
- 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 current AChEI 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 Idalopirdine 60 mg (or 30 mg) Idalopirdine Idalopirdine adjunct to base treatment with an AChEI Placebo Placebo Placebo adjunct to base treatment with an AChEI
- Primary Outcome Measures
Name Time Method Change in Cognition Baseline and 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 Global Impression Baseline and 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 Daily Functioning Baseline and 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 Individual Behavioural Disturbance Items Baseline and 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 Behavioural Disturbance Baseline and 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 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 NPI score is the frequency ratings multiplied by the severity ratings and ranges from 0 to 144 (higher score indicates 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 Health-related Quality of Life (EQ-5D) Utility Score Baseline and 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 NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at Baseline Baseline and 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.Change in Cognitive Aspects of Mental Function Baseline and 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 VAS) Baseline and 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 (107)
US608
🇺🇸Deerfield Beach, Florida, United States
DE616
🇩🇪Unterhaching, Germany
DE601
🇩🇪Munich, Germany
DE609
🇩🇪Berlin, Germany
DE605
🇩🇪Homburg, Germany
BR607
🇧🇷Rio de Janeiro, Brazil
CZ605
🇨🇿Havlickuv Brod, Czechia
CZ603
🇨🇿Plzen, Czechia
CZ607
🇨🇿Praha 10 - Strasnice, Czechia
AU606
🇦🇺Newcastle, Australia
US621
🇺🇸Albany, New York, United States
DE610
🇩🇪Bad Honnef, Germany
DE608
🇩🇪Karlstadt, Germany
US604
🇺🇸Oxnard, California, United States
AU604
🇦🇺Kanwal, Australia
CZ602
🇨🇿Chocen, Czechia
US633
🇺🇸Charlotte, North Carolina, United States
DE602
🇩🇪Mittweida, Germany
US601
🇺🇸Farmington Hills, Michigan, United States
AU601
🇦🇺West Perth, Australia
IL605
🇮🇱Bat Yam, Israel
CZ601
🇨🇿Prague, Czechia
US606
🇺🇸Prairie Village, Kansas, United States
DE612
🇩🇪Bad Homburg, Germany
DE603
🇩🇪Ulm, Germany
DE617
🇩🇪Berlin, Germany
BR609
🇧🇷Itapira, Brazil
KR603
🇰🇷Seoul, Korea, Republic of
BR608
🇧🇷Belo Horizonte, Brazil
TR607
🇹🇷Samsun, Turkey
US618
🇺🇸Norristown, Pennsylvania, United States
ES611
🇪🇸Bilbao, Spain
ES610
🇪🇸Sant Cugat del Vallès, Spain
AU603
🇦🇺Caulfield, Australia
AU602
🇦🇺Heidelberg West, Australia
AU610
🇦🇺Woodville south, Australia
US626
🇺🇸Costa Mesa, California, United States
US611
🇺🇸Elkhart, Indiana, United States
US632
🇺🇸Staten Island, New York, United States
US630
🇺🇸Toms River, New Jersey, United States
US607
🇺🇸Saint Louis, Missouri, United States
DE604
🇩🇪Erbach, Germany
CZ608
🇨🇿Chocen, Czechia
DE611
🇩🇪Freiburg, Germany
CZ604
🇨🇿Praha 6, Czechia
CZ606
🇨🇿Kladno, Czechia
DE606
🇩🇪Rostock, Germany
ES607
🇪🇸Valencia, Spain
TR605
🇹🇷Istanbul, Turkey
IL604
🇮🇱Holon, Israel
IL602
🇮🇱Ramat Gan, Israel
KR601
🇰🇷Seongnam-si, Korea, Republic of
ES603
🇪🇸Barcelona, Spain
GB601
🇬🇧Brentford, United Kingdom
KR604
🇰🇷Seoul, Korea, Republic of
ES612
🇪🇸Burgos, Spain
TR601
🇹🇷Istanbul, Turkey
TR603
🇹🇷İstanbul, Turkey
TR606
🇹🇷Izmir, Turkey
GB603
🇬🇧Northampton, United Kingdom
ES604
🇪🇸Barcelona, Spain
ES608
🇪🇸Barcelona, Spain
ES602
🇪🇸Lleida, Spain
ES605
🇪🇸Terrassa, Spain
SK602
🇸🇰Svidnik, Slovakia
CH605
🇨🇭Lausanne, Switzerland
ES601
🇪🇸Barcelona, Spain
ES613
🇪🇸Madrid, Spain
ES606
🇪🇸Sevilla, Spain
US625
🇺🇸Bellflower, California, United States
US627
🇺🇸Santa Ana, California, United States
US616
🇺🇸Hialeah, Florida, United States
US631
🇺🇸Port Charlotte, Florida, United States
US603
🇺🇸North Palm Beach, Florida, United States
US622
🇺🇸Elk Grove Village, Illinois, United States
US613
🇺🇸Lawrenceville, New Jersey, United States
AU609
🇦🇺Glen Iris, Australia
DE607
🇩🇪Gelsenkirchen, Germany
KR602
🇰🇷Seoul, Korea, Republic of
RS603
🇷🇸Kragujevac, Serbia
RS601
🇷🇸Novi Sad, Serbia
SG602
🇸🇬Singapore, Singapore
TR602
🇹🇷Balova, Turkey
US609
🇺🇸Danbury, Connecticut, United States
IL601
🇮🇱Haifa, Israel
MX605
🇲🇽Monterrey, Mexico
CH603
🇨🇭Biel, Switzerland
MX603
🇲🇽Monterrey, Mexico
US612
🇺🇸Mesa, Arizona, United States
US635
🇺🇸Manchester, New Jersey, United States
US614
🇺🇸Norwalk, Connecticut, United States
IL603
🇮🇱Tel Aviv, Israel
MX604
🇲🇽Monterrey, Mexico
SK605
🇸🇰Bratislava, Slovakia
SK604
🇸🇰Rimavska Sobota, Slovakia
MX602
🇲🇽Mexico, Mexico
MX601
🇲🇽Monterrey, Mexico
MX606
🇲🇽Saltillo, Mexico
RS602
🇷🇸Belgrade, Serbia
SG601
🇸🇬Singapore, Singapore
SK601
🇸🇰Banska Bystrica, Slovakia
SK603
🇸🇰Bratislava, Slovakia
CH602
🇨🇭Les Acacias, Switzerland
CH601
🇨🇭Schlieren, Switzerland
US620
🇺🇸Miami, Florida, United States
US619
🇺🇸Houston, Texas, United States
US623
🇺🇸Oklahoma City, Oklahoma, United States