Ignite Creation Date:
2024-05-05 @ 12:03 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00230997
Status:
COMPLETED
Last Update Posted:
2005-12-16
First Post:
2005-09-29
Brief Title:
Safety and Efficacy of Galantamine in Patients With Dementia With Lewy Bodies
Sponsor:
Neurological Research Center
Organization:
Neurological Research Center
Study Overview
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
Status Verified Date:
2005-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 mgday 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
This is an open-label 24-week investigator initiated study to evaluate the safety and efficacy of galantamine 16 8 to 24 mgday 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
Detailed 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 mgday for DLB patients should be sufficient to show efficacy Since galantamine has previously been shown to be efficacious in the domains of behavior cognition ADLs 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 IRBIEC approved Informed Consent Subjects eligibility for the trial will be determined on the basis of the inclusionexclusion criteria and from the results of the following pre-treatment assessments
Medical history
Complete neurological examination
Complete physical examination
CT ScanMRI
Vital signs blood pressureheart 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 pressureheart 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
AEs
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 pressureheart rate Weight
Concomitant medications
NPI-12
PSQI
Fluctuation scales
Dispense medication See table
AEs
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 pressureheart 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
AEs
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 pressureheart 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
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 mgday for DLB patients should be sufficient to show efficacy Since galantamine has previously been shown to be efficacious in the domains of behavior cognition ADLs 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 IRBIEC approved Informed Consent Subjects eligibility for the trial will be determined on the basis of the inclusionexclusion criteria and from the results of the following pre-treatment assessments
Medical history
Complete neurological examination
Complete physical examination
CT ScanMRI
Vital signs blood pressureheart 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 pressureheart 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
AEs
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 pressureheart rate Weight
Concomitant medications
NPI-12
PSQI
Fluctuation scales
Dispense medication See table
AEs
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 pressureheart 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
AEs
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 pressureheart 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None