Clinical trial NCT00679627: A Study of Galantamine Used to Treat Patients With Mild to Moderate Alzheimer's Disease
Official title: A Randomized, Double-Blind, Placebo-controlled Trial of Long-term (2-year) Treatment of Galantamine in Mild to Moderately-Severe Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Galantamine
Dementia, Alzheimer type
Memory loss
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2008-05-19
Enrollment: 2051
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the effectiveness and safety of 2 years of treatment with galantamine as compared with placebo of patients who have mild to moderately severe Alzheimer's disease (AD).

Detailed description: This is a long-term (2-year), randomized (patients will be assigned to treatment by chance), double blind (neither the physician nor the patient will know which treatment is assigned) study of galantamine versus placebo in subjects with mild to moderately-severe AD. Approximately 2,000 patients will participate in this study. The study length for each patient is approximately 25.5 months. The study consists of 3 phases: a pretreatment phase, a treatment phase, and a posttreatment phase. The pretreatment phase includes a 2-week screening period (to obtain a patient's and his or her caregiver's informed consent and to confirm eligibility for the study) and a baseline visit at which subjects will be randomly assigned, in a 1 to 1 ratio, to receive either galantamine or placebo once a day in the morning. Study drug will first be dispensed at the baseline visit. The treatment phase is composed of a titration period (the study drug will be introduced gradually) and a maintenance period and includes 9 visits (3 of which are conducted by telephone). The titration period is 12 weeks long, and visits occur about every 28 days. In the first 4 weeks of the titration period, subjects will receive either 8 mg galantamine or matching placebo, and this dose will be increased to 16 mg galantamine or placebo in the second 4 weeks. The dose will then be increased to 24 mg galantamine or placebo for the final 4 weeks of the titration period if the investigator believes the subject will benefit from and will safely tolerate 24 mg/day. If not, the subject may continue to receive 16 mg galantamine or placebo through the end of the titration period. After the titration period, subjects will enter the maintenance period and continue to take study drug at the dosage they received at the end of the titration period. This dosage may be continued through the end of the study or may be changed once (either up from 16 to 24 mg or down from 24 to 16 mg), depending upon the benefit and the safety of such a change for the individual patient as judged by the investigator. No dosage will exceed 24 mg/day. The posttreatment phase includes an End-of-Study Visit that occurs at the end of the maintenance period. A follow-up telephone contact (interview) is conducted 1 month after the End-of-Study Visit. The effectiveness of galantamine will be evaluated using the following tools: the Mini-Mental State Examination (MMSE); the Disability Assessment in Dementia (DAD); and the Assessment of Patient Accommodation Status and Caregiver Burden (APAS CarB). Safety evaluations for the study include the monitoring of vital status and institutionalization status, adverse events, vital signs, weight, physical and neurologic examinations. A Data Safety Monitoring Board, external to the company, has been commissioned for this study to monitor the progress of the study and to ensure that the safety of patients is not compromised. The effectiveness hypothesis of this study is that galantamine, 16 to 24 mg per day, is superior to placebo in reducing cognitive decline from baseline (start of study drug) as measured by the MMSE over the course of 2 years. The safety hypothesis is that the mortality rate in the galantamine 16 to 24 mg per day treatment group will be the same as that in the placebo group over the course of 2 years.

Eligibility criteria: Inclusion Criteria:

* Outpatients
* diagnosed with mild to moderately-severe, probable or possible AD, established in accordance with the criteria defined by the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease Related Disorders Association or the Diagnostic and Statistical Manual, Fourth Edition
* living with or have regular and frequent visits from a responsible caregiver.

Exclusion Criteria:

* Neurodegenerative disorders other than AD, such as Parkinson's Disease, Frontotemporal Dementia or Huntington's disease
* Any of specified conditions which may contribute to dementia
* any of specified coexisting diseases, including significant cardiovascular disease.

Primary outcomes:
measure: Change From Baseline in the Mini-Mental State Examination (MMSE) Score
timeFrame: Baseline, Month 24
measure: The Number of Deaths Reported in Participants
timeFrame: Up to 2 years
Secondary outcomes:
measure: Change From Baseline in the Mini-Mental State Examination (MMSE) Score
timeFrame: Baseline, Month 6
measure: Change From Baseline in Disability Assessment in Dementia (DAD) Scores
timeFrame: Baseline, Month 24
measure: Change From Baseline in Patient Accommodation Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)
timeFrame: Baseline, Months 12 and 24
measure: Change From Baseline in Caregiver Time Spent With the Patient Measured Using the Assessment of Subject Accommodation Status and Caregiver Burden (APAS-CarB)
timeFrame: Baseline, Months 12 and 24
measure: Change From Baseline in Institutional Status
timeFrame: Baseline, Month 24
measure: Change From Baseline in the Mini-Mental State Examination (MMSE) Subscales (Orientation, Registration, Attention and Calculation, Recall, and Language)
timeFrame: Baseline, Month 24
measure: Change From Baseline in the Disability Assessment in Dementia (DAD) Subscales (Initiation, Planning and Organization, Effective Performance, Basic, Instrumental, and Leisure)
timeFrame: Baseline, Month 24
Other outcomes:
Locations:
city: Hradec Kralove
country: Czech Republic
city: Mìlník 1
country: Czech Republic
city: Olomouc
country: Czech Republic
city: Ostrava 3
country: Czech Republic
city: Ostrava
country: Czech Republic
city: Praha 2
country: Czech Republic
city: Praha 8
country: Czech Republic
city: Tallinn N/A
country: Estonia
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Viljandi N/A
country: Estonia
city: Vorumaa
country: Estonia
city: Limoges
country: France
city: Bad Aibling
country: Germany
city: Bad Homburg
country: Germany
city: Bad Honnef
country: Germany
city: Bamberg
country: Germany
city: Berlin
country: Germany
city: Bielefeld
country: Germany
city: Bochum
country: Germany
city: Butzbach
country: Germany
city: Franfurt
country: Germany
city: Fürth
country: Germany
city: Gelsenkirchen
country: Germany
city: Göttingen
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Hattingen
country: Germany
city: Karlstadt
country: Germany
city: Leverkusen
country: Germany
city: Lüneburg
country: Germany
city: Mittweida
country: Germany
city: Mönchengladbach
country: Germany
city: Nürnberg
country: Germany
city: Oldenburg
country: Germany
city: Ulm
country: Germany
city: Unterhaching
country: Germany
city: Westerstede
country: Germany
city: Wiesbaden
country: Germany
city: Athens
country: Greece
city: Heraklion Crete
country: Greece
city: Thessalonikis
country: Greece
city: Riga
country: Latvia
city: Kaunas
country: Lithuania
city: Siauliai
country: Lithuania
city: Vilnius
country: Lithuania
city: Arad
country: Romania
city: Bucharest Sector 5
country: Romania
city: Bucharest
country: Romania
city: Cluj-Napoca
country: Romania
city: Constanta
country: Romania
city: Craiova
country: Romania
city: Iasi
country: Romania
city: Tg Mures
country: Romania
city: Ekaterinburg
country: Russian Federation
city: Kazan N/A
country: Russian Federation
city: Kazan
country: Russian Federation
city: Kirov
country: Russian Federation
city: Krasnodar N/A
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Lipetsk
country: Russian Federation
city: Moscow Russia
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizny Novgorod
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Rostov-On-Don
country: Russian Federation
city: Samara
country: Russian Federation
city: Saratov
country: Russian Federation
city: Smolensk Region N/A
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St-Petersburg
country: Russian Federation
city: St.Petersburg
country: Russian Federation
city: Tomsk Na
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Bratislava
country: Slovakia
city: Dubnica Nad Vahom
country: Slovakia
city: Kosice
country: Slovakia
city: Plesivec
country: Slovakia
city: Senkvice
country: Slovakia
city: Spisska Nova Ves
country: Slovakia
city: Vranov Nad Toplou
country: Slovakia
city: Kamnik
country: Slovenia
city: Lesce
country: Slovenia
city: Ljubljana
country: Slovenia
city: Maribor
country: Slovenia
city: Chernivtsy
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkov
country: Ukraine
city: Kherson
country: Ukraine
city: Kiev
country: Ukraine
city: Kyiv
country: Ukraine
city: Lviv
country: Ukraine
city: Lvov
country: Ukraine
city: Odessa
country: Ukraine
city: Poltava
country: Ukraine
city: Simferopol
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Vinnitsa
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Hager K, Baseman AS, Nye JS, Brashear HR, Han J, Sano M, Davis B, Richards HM. Effect of concomitant use of memantine on mortality and efficacy outcomes of galantamine-treated patients with Alzheimer's disease: post-hoc analysis of a randomized placebo-controlled study. Alzheimers Res Ther. 2016 Nov 15;8(1):47. doi: 10.1186/s13195-016-0214-x.
citation: Hager K, Baseman AS, Nye JS, Brashear HR, Han J, Sano M, Davis B, Richards HM. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease. Neuropsychiatr Dis Treat. 2014 Feb 21;10:391-401. doi: 10.2147/NDT.S57909. eCollection 2014.