Study of Idalopirdine in Patients With Mild - Moderate Alzheimer's Disease Treated With an Acetylcholinesterase Inhibitor

Phase 3CompletedNCT02006654

H. Lundbeck A/S734 enrolled

Overview

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

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

734

Conditions

Alzheimer's Disease

Interventions

PlaceboDRUG

Once daily, matching placebo capsules, orally

IdalopirdineDRUG

Once daily, encapsulated tablets, orally

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

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 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. 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 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.

Locations (107)

Outcomes

Primary Outcomes

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).

Time frame: Baseline and Week 24

Secondary Outcomes

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).

Time frame: Baseline and Week 24

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).

Time frame: Baseline and Week 24

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 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).

Data from ClinicalTrials.gov

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US612

Mesa, Arizona, United States

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Bellflower, California, United States

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Costa Mesa, California, United States

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Oxnard, California, United States

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Santa Ana, California, United States

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Danbury, Connecticut, United States

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Norwalk, Connecticut, United States

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Deerfield Beach, Florida, United States

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Hialeah, Florida, United States

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Miami, Florida, United States

...and 97 more locations

Time frame: Baseline and Week 24

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.

Time frame: Baseline and Week 24

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.

Time frame: Baseline and Week 24

Clinical Improvement

Clinical response at Week 24 (based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes \[change in ADAS-cog below or equal to -4, change in ADCS-ADL23 at least 0, and ADCS-CGIC below or equal to 4\])

Time frame: Week 24

Clinical Worsening

Clinical worsening at Week 24 (Based on pre-specified ADAS-cog, ADCS-ADL23, and ADCS-CGIC changes \[change in ADAS-cog above or equal to 4, change in ADCS-ADL23 below 0, and ADCS-CGIC above 4\])

Time frame: Week 24

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).

Time frame: Baseline and Week 24

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.

Time frame: Baseline and Week 24

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).

Time frame: Baseline and Week 24