Safety and Efficacy of Galantamine in Patients With Dementia With Lewy Bodies

Lewy Body Disease Clinical Trial

Official title: An Open Label 24-Week, Flexible Dose Trial to Assess the Safety and Efficacy of Galantamine in Patients With Dementia With Lewy Bodies

Status Completed

Clinical Trial Summary

TRIAL SUMMARY:

This is an open-label, 24-week, investigator initiated study to evaluate the safety and efficacy of galantamine (16 8 to 24 mg/day; flexible dosing) in the treatment of Dementia with Lewy bodies. The primary efficacy variables will be the NPI -12, the COGDRAS tests of attention and visuospatial orientation, and the ADCS-CGIC. The secondary efficacy variables will be the MMSE, ADCS-ADL-Inventory, ADAS-Cog, PSQI, and the use of concomitant rescue antipsychotic medication. PET scanning will be obtained on 10 patients at one site. An interim analysis will also be performed. Safety outcome measures will be adverse event reports, vital signs, physical examinations, ECG, laboratory parameters and the UPDRS (motor subscale).

Clinical Trial Description

TRIAL DESIGN

1. Rationale

In a previously published study of DLB treated with rivastigmine, efficacy was seen to be maximized at 20 weeks in multiple parameters compared to placebo. The efficacy was seen in the NPI - 4 as well as the NPI -10, MMSE and a Computerized Cognitive Assessment Systems Score5. There was no change in UPDRS score. The efficacy of rivastigmine for patients with DLB responding greater than 30 percent in behavioral measures was equal to or better than most studies of antipsychotic medications used for behavioral abnormalities in DLB and AD patients.

Since the titration for galantamine involves less time than the titration for rivastigmine, an interim analysis may show efficacy at 12 weeks. However, for complete efficacy and safety evaluations, a 24-week treatment for galantamine is preferable. Since the cholinergic deficits in DLB patients is more profound than that for AD patients, the dose range of 16 8 to 24 mg/day for DLB patients should be sufficient to show efficacy. Since galantamine has previously been shown to be efficacious in the domains of behavior, cognition, ADL's and global assessment in AD patients, we expect efficacy to be shown similarly and perhaps to a greater extent in DLB patients.

TREATMENT OF SUBJECTS

There will be seven visits in this 24-week treatment trial with galantamine for DLB. For all visits a time window of +/- 3 days relative to baseline visit V2 is applicable.

Screen: Visit 1 (-4 week – 0)

At visit 1 (V1) subjects will be evaluated for their suitability for enrollment. It is acceptable for this visit to be conducted on more than one day, although it should not be done over longer than a week. Prior to the conduct of any trial related procedures a complete explanation (both verbally and written) of the nature and purpose of the trial will be given by the Investigator (or designee). The subject will be requested to sign and date the IRB/IEC approved Informed Consent. Subject’s eligibility for the trial will be determined on the basis of the inclusion/exclusion criteria, and from the results of the following pre-treatment assessments:

• Medical history

• Complete neurological examination

• Complete physical examination

• CT Scan/MRI

• Vital signs (blood pressure/heart rate)

• Weight

• Height

• ECG

• Complete chemistry panel, hematology, B12, folate, RPR, thyroid panels including TSH (if not done within the last 3 months)

• Urine pregnancy test (if applicable)

• Concomitant medications

• Mini Mental State Exam (MMSE)

• NPI-12

• PSQI

• Modified Hachinski Ischemic Scale (MHIS)

Baseline: Visit 2 (Week 0)

At the beginning of this visit the Investigator should review all test results from Visit 1, this will include the completion of eligibility criteria. If patient is eligible to continue in the trial, the following assessments will be carried out:

• Brief physical examination

• Vital signs (blood pressure/heart rate)

• Weight

• Concomitant medications

• MMSE

• NPI-12

• ADAS-Cog

• ADCS-CGIC

• FDG-PET*

• PSQI

• ADCS-ADL inventory

• Fluctuation scales

• UPDRS

• COGDRAS

• Dispense medication (See table)

• AE’s

Titration: Visits 3 (Week 4), Visit 4 (Week 8)

During the titration visits (Visit 3 and Visit 4) the following assessments will be done:

• Brief physical examination

• Vital signs (blood pressure/heart rate) • Weight

• Concomitant medications

• NPI-12

• PSQI

• Fluctuation scales

• Dispense medication (See table)

• AE’s

• Drug accountability

Maintenance: Visit 5 (Week 12), Visit 6 (Week 20)

Subjects who have completed the titration phase will continue the 12 week maintenance phase. On clinic visit days subjects will have the following assessments:

• Brief physical examination

• Vital signs (blood pressure/heart rate)

• Weight

• Concomitant medications

• MMSE (Visit 5 only)

• NPI-12

• ADAS-Cog (Visit 5 only)

• PSQI

• ADCS-ADL inventory (Visit 5 only)

• Fluctuation scales

• UPDRS (Visit 5 only)

• COGDRAS (Visit 5 only)

• Dispense medication (See table)

• AE’s

• Drug Accountability

• Efficacy measures (Visit 5 only)

Final Visit: Visit 7 (Week 24)

The subject will be scheduled for a clinic visit to perform the final assessments. The following assessments will be carried out:

• Complete neurological examination

• Complete physical examination

• Vital signs (blood pressure/heart rate)

• Weight

• ECG

• Complete chemistry panel and hematology

• Urine pregnancy test (if applicable)

• Concomitant medications

• Mini Mental State Exam (MMSE)

• NPI-12

• ADAS-Cog

• ADCS-CGIC

• FDG-PET*

• PSQI

• ADCS-ADL inventory

• Fluctuation scales

• UPDRS

• COGDRAS

• Drug accountability ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lewy Body Disease

• NCT number: NCT00230997
• Study type: Interventional
• Source: Neurological Research Center
• Status: Completed
• Phase: Phase 3
• Start date: December 2002
• Completion date: August 2004