MedPath

Idalopirdine in Patients With Mild-moderate Alzheimer's Disease Treated With Donepezil

Phase 3
Completed
Conditions
Alzheimer's Disease
Interventions
Drug: Placebo
Registration Number
NCT02006641
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 10 mg/day or 30 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
858
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Idalopirdine 30 mgIdalopirdineIdalopirdine adjunct to 10 mg Donepezil
Idalopirdine 10 mgIdalopirdineIdalopirdine adjunct to 10 mg Donepezil
PlaceboPlaceboPlacebo adjunct to 10 mg Donepezil
Primary Outcome Measures
NameTimeMethod
Change in CognitionBaseline 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
NameTimeMethod
Change in Individual Behavioural Disturbance ItemsBaseline 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 NPI Anxiety Item Score in Patients With an NPI Anxiety Item Score of at Least 2 at BaselineBaseline 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 Daily FunctioningBaseline 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).

Number of Participants With Clinical WorseningWeek 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 Global ImpressionBaseline 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 Behavioural DisturbanceBaseline 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 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).

Number of Participants With Clinical ImprovementWeek 24

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

Change in Cognitive Aspects of Mental FunctionBaseline 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) Utility ScoreBaseline 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 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 (162)

IL302

🇮🇱

Haifa, Israel

US305

🇺🇸

Carson, California, United States

US346

🇺🇸

Costa Mesa, California, United States

US322

🇺🇸

Anaheim, California, United States

US327

🇺🇸

Fullerton, California, United States

US307

🇺🇸

Redlands, California, United States

US351

🇺🇸

Oceanside, California, United States

US315

🇺🇸

Lomita, California, United States

US301

🇺🇸

Santa Rosa, California, United States

US308

🇺🇸

Delray Beach, Florida, United States

US320

🇺🇸

Hallandale Beach, Florida, United States

US347

🇺🇸

Hialeah, Florida, United States

US340

🇺🇸

Lake Worth, Florida, United States

US335

🇺🇸

Naples, Florida, United States

US345

🇺🇸

Orange City, Florida, United States

US309

🇺🇸

Palm Beach Gardens, Florida, United States

US304

🇺🇸

Atlanta, Georgia, United States

US302

🇺🇸

Sunrise, Florida, United States

US360

🇺🇸

Augusta, Georgia, United States

US318

🇺🇸

Decatur, Georgia, United States

US350

🇺🇸

Belmont, Massachusetts, United States

US310

🇺🇸

Saint Paul, Minnesota, United States

US330

🇺🇸

Creve Coeur, Missouri, United States

US312

🇺🇸

Staten Island, New York, United States

US316

🇺🇸

Charlotte, North Carolina, United States

US323

🇺🇸

Cincinnati, Ohio, United States

US306

🇺🇸

Columbus, Ohio, United States

US333

🇺🇸

Oklahoma City, Oklahoma, United States

US352

🇺🇸

Lakewood, Ohio, United States

US314

🇺🇸

Allentown, Pennsylvania, United States

US324

🇺🇸

Pittsburgh, Pennsylvania, United States

US325

🇺🇸

Reading, Pennsylvania, United States

US341

🇺🇸

Pittsburgh, Pennsylvania, United States

US343

🇺🇸

Fort Worth, Texas, United States

AR303

🇦🇷

Banfield, Argentina

AR304

🇦🇷

Ciudad Autonoma Buenos Aires, Argentina

AR309

🇦🇷

Cordoba, Argentina

BR309

🇧🇷

Curitiba, Brazil

BR301

🇧🇷

Rio de Janeiro, Brazil

BR306

🇧🇷

Rio de Janeiro, Brazil

CA302

🇨🇦

Kelowna, Canada

CA301

🇨🇦

Halifax, Canada

BR308

🇧🇷

San Paolo, Brazil

CA306

🇨🇦

Montreal, Canada

CA305

🇨🇦

Toronto, Canada

CA304

🇨🇦

Qubec, Canada

CA303

🇨🇦

Sherbrooke, Canada

HR304

🇭🇷

Zabok, Croatia

HR302

🇭🇷

Zagreb, Croatia

CZ305

🇨🇿

Brno, Czechia

CZ310

🇨🇿

Praha 10 - Strasnice, Czechia

CZ306

🇨🇿

Chocen, Czechia

CZ309

🇨🇿

Chocen, Czechia

CZ308

🇨🇿

Pardubice, Czechia

CZ304

🇨🇿

Praha 10, Czechia

CZ307

🇨🇿

Praha 2, Czechia

CZ301

🇨🇿

Praha 6, Czechia

CZ303

🇨🇿

Praha 6, Czechia

CZ302

🇨🇿

Rychnov nad Kneznou, Czechia

EE303

🇪🇪

Tallin, Estonia

FR301

🇫🇷

Bordeaux, France

FR308

🇫🇷

Bron, France

FR304

🇫🇷

Dijon, France

FR309

🇫🇷

Elancourt, France

FR302

🇫🇷

Marseille cedex 5, France

FR307

🇫🇷

Colmar cedex, France

FR306

🇫🇷

Reims, France

FR303

🇫🇷

Nice Cedex 1, France

FR305

🇫🇷

Rouen, France

HU305

🇭🇺

Budapest, Hungary

HU303

🇭🇺

Gyor, Hungary

HU302

🇭🇺

Szeged, Hungary

IL303

🇮🇱

Holon, Israel

IT306

🇮🇹

Brescia, Italy

IT311

🇮🇹

Genova, Italy

IL304

🇮🇱

Ramat Gan, Israel

IT312

🇮🇹

Monza, Italy

IT313

🇮🇹

Palermo, Italy

IT307

🇮🇹

Perugia, Italy

IT308

🇮🇹

Roma, Italy

IT304

🇮🇹

Torino, Italy

KR303

🇰🇷

Busan, Korea, Republic of

IT305

🇮🇹

Roma, Italy

IT310

🇮🇹

Torrette, Italy

KR308

🇰🇷

Seongnam-si, Korea, Republic of

KR301

🇰🇷

Incheon, Korea, Republic of

KR304

🇰🇷

Seoul, Korea, Republic of

KR302

🇰🇷

Seoul, Korea, Republic of

KR305

🇰🇷

Seoul, Korea, Republic of

KR306

🇰🇷

Seoul, Korea, Republic of

KR309

🇰🇷

Seoul, Korea, Republic of

KR307

🇰🇷

Seoul, Korea, Republic of

LT304

🇱🇹

Vilnius, Lithuania

PL301

🇵🇱

Bialystok, Poland

PL309

🇵🇱

Krakow, Poland

PL302

🇵🇱

Lodz, Poland

PL303

🇵🇱

Poznan, Poland

TW304

🇨🇳

Taipei, Taiwan

TW305

🇨🇳

Taipei, Taiwan

GB307

🇬🇧

Amersham, United Kingdom

GB301

🇬🇧

Glasgow, United Kingdom

GB303

🇬🇧

London, United Kingdom

GB308

🇬🇧

London, United Kingdom

GB306

🇬🇧

Plymouth, United Kingdom

GB305

🇬🇧

Preston, United Kingdom

GB304

🇬🇧

Southampton, United Kingdom

GB309

🇬🇧

Warrington, United Kingdom

GB302

🇬🇧

Swindon, United Kingdom

US342

🇺🇸

Fayetteville, Arkansas, United States

US337

🇺🇸

New London, Connecticut, United States

US332

🇺🇸

Stamford, Connecticut, United States

US334

🇺🇸

Lake Charles, Louisiana, United States

US321

🇺🇸

Hattiesburg, Mississippi, United States

US339

🇺🇸

Manchester, New Jersey, United States

US319

🇺🇸

Port Royal, South Carolina, United States

US356

🇺🇸

Cordova, Tennessee, United States

AR301

🇦🇷

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

AR315

🇦🇷

Ciudad Autonoma Buenos Aires, Argentina

AR312

🇦🇷

Ciudad Autonoma de Buenos Aires, Argentina

AR307

🇦🇷

Córdoba, Argentina

AR305

🇦🇷

Godoy Cruz, Argentina

AR310

🇦🇷

Mendoza, Argentina

AR302

🇦🇷

Santa Fe, Argentina

AR306

🇦🇷

Santiago del Estero, Argentina

HR301

🇭🇷

Zagreb, Croatia

HR303

🇭🇷

Zagreb, Croatia

EE301

🇪🇪

Tallinn, Estonia

EE302

🇪🇪

Tartu, Estonia

FI302

🇫🇮

Kuopio, Finland

FI303

🇫🇮

Oulu, Finland

FI301

🇫🇮

Turku, Finland

HU304

🇭🇺

Budapest, Hungary

HU301

🇭🇺

Esztergom, Hungary

IE301

🇮🇪

Cork, Ireland

LT302

🇱🇹

Kaunas, Lithuania

LT303

🇱🇹

Kaunas, Lithuania

LT301

🇱🇹

Vilnius, Lithuania

PL304

🇵🇱

Bydgoszcz, Poland

PL308

🇵🇱

Gdynia, Poland

PL310

🇵🇱

Lubin, Poland

PL306

🇵🇱

Lublin, Poland

PL307

🇵🇱

Oswiecim, Poland

PT301

🇵🇹

Amadora, Portugal

PT302

🇵🇹

Coimbra, Portugal

TW301

🇨🇳

Kaohsiung, Taiwan

TW302

🇨🇳

Kaohsiung, Taiwan

TW303

🇨🇳

Taichung, Taiwan

IT309

🇮🇹

Brescia, Italy

IT302

🇮🇹

Naples, Italy

IT301

🇮🇹

Pisa, Italy

US338

🇺🇸

Phoenix, Arizona, United States

US303

🇺🇸

Miami, Florida, United States

US313

🇺🇸

Miami, Florida, United States

US344

🇺🇸

Boston, Massachusetts, United States

US349

🇺🇸

Cleveland, Ohio, United States

US354

🇺🇸

Houston, Texas, United States

BR307

🇧🇷

Curitiba, Brazil

US336

🇺🇸

Winston-Salem, North Carolina, United States

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