Ignite Creation Date:
2024-05-05 @ 5:13 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00416169
Status:
COMPLETED
Last Update Posted:
2011-06-08
First Post:
2006-12-22
Brief Title:
A Pilot Study to Explore the Safety and Tolerability of Galantamine HBr in the Treatment of Pick ComplexFrontotemporal Dementia
Sponsor:
Johnson Johnson Pharmaceutical Research Development LLC
Organization:
Johnson Johnson Pharmaceutical Research Development LLC
Study Overview
Official Title:
An Open Pilot Study to Evaluate the Safety and Efficacy of Galantamine in the Treatment of Picks DiseaseFrontotemporal Dementia Pick Complex
Status:
COMPLETED
Status Verified Date:
2011-01
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:
The purpose of this study is to explore the safety and tolerability and the efficacy of galantamine treatment in subjects with Pick Complex Frontotemporal Dementia PCFTD The safety and tolerability of galantamine therapy will be assessed over the entire treatment period 26 weeks The 8 week withdrawal period will be used to confirm the safety of galantamine withdrawal in this subject group and it impact on any symptom improvement achieved during the first 18 weeks of galantamine treatment symptom improvement would be expected to stabilize or decline on withdrawal of an effective therapy
The primary efficacy objective is to explore the effect of galantamine on behavior as measured by the Frontal Behavioral Inventory during the randomized withdrawal period In addition for subjects with primary progressive aphasia limited ability for languages the effects of galantamine on language will be explored using the Aphasia Quotient of the Western Aphasia Battery and for all subjects the Clinical Global Impressions will be used to explore global change
The primary efficacy objective is to explore the effect of galantamine on behavior as measured by the Frontal Behavioral Inventory during the randomized withdrawal period In addition for subjects with primary progressive aphasia limited ability for languages the effects of galantamine on language will be explored using the Aphasia Quotient of the Western Aphasia Battery and for all subjects the Clinical Global Impressions will be used to explore global change
Detailed Description:
Pick Complex PC and Frontotemporal Dementia FTD are a group of neurodegenerative dementias initially characterized by frontotemporal lobar atrophy that have overlapping clinical presentations and pathologic findings Although the pathogenesis of Pick ComplexFrontotemporal Dementia remains unknown and the neurotransmitter changes in Pick ComplexFrontotemporal Dementia are not well characterized there is evidence for decreased cholinergic receptor binding in several cortical regions and decreased serotonin binding in the hypothalamus frontal cortex and temporal cortex Galantamine is a reversible cholinesterase inhibitor Recent studies indicate that galantamine is also an allosteric modulator at nicotinic cholinergic receptor sites This nicotinic modulation appears to not only potentiate the response to acetylcholine binding but also to modulate release of several other neurotransmitters including serotonin This pilot study will explore the safety and tolerability and efficacy of galantamine 8 mg and 12 mg twice a day treatment in subjects with Pick ComplexFrontotemporal Dementia The study comprises an 18 week open label galantamine treatment phase followed by an 8 week randomized double blind placebo controlled withdrawal phase The safety and tolerability of galantamine therapy will be explored during both the open label and randomized withdrawal periods The 8 week randomized withdrawal period will be used to confirm the safety of galantamine withdrawal in this subject group and its impact on possible symptom improvement achieved during the open label period as a marker for efficacy
The expectation is that subjects who remain on galantamine for the additional 8 weeks will continue to improve or will remain stable with regard to their behavior language cognition and global function whereas subjects who are assigned to placebo will show a decline in some of these functions This approach will allow an assessment of the effects of galantamine treatment challenge and galantamine withdrawal de-challenge
This study will involve a maximum of 40 subjects with Pick ComplexFrontotemporal Dementia Subjects who meet the inclusion and exclusion criteria will receive galantamine 4 mg twice a day for 4 weeks followed by 8 mg twice a day for 4 weeks At 8 weeks the dose of galantamine will be maintained at 8 mg or increased to 12 mg twice a day based on tolerability At the end of 12 weeks the dose of galantamine will be maintained at 8 or 12 mg twice a day or reduced to 8 mg twice a day based on tolerability The dose will be fixed for the remainder of the open label treatment period Following 18 weeks of galantamine treatment subjects will be randomly assigned 11 to continued treatment with galantamine at the same dose or placebo for an additional 8 weeks Subjects and caregivers will be contacted by phone during the study and encouraged to contact the site at any time if they have concerns If the subjects symptoms appear to be substantially worsening and the investigator determines that the subject has deteriorated he will advise the subject and caregiver about possible early completion of the study early escape Subjects electing early escape will complete final efficacy and safety assessments then discontinue study medication Once they have completed the study they will begin the treatment of their choice in consultation with their physician Subjects will be seen for assessment at Visit 1 screening Visit 2 baseline Visits 3 and 4 12 and 18 weeks after the start of open label galantamine treatment and Visit 5 8 weeks after the start of the double blind withdrawal period or at early escape or upon premature discontinuation The subject and caregiver will return for an unscheduled visit if in the judgment of the investigator the subject requires clinical assessment between visits
Subject selection criteria will ensure inclusion of subjects who have a clinical diagnosis of Pick ComplexFrontotemporal Dementia established by published consensus criteria and supported by neuroradiologic confirmation The subjects selected for the study will have a diagnosis of primary progressive aphasia or frontotemporal dementia
Safety and tolerability will be monitored by assessment of adverse events electrocardiograms physical examinations blood pressure heart rate weight and laboratory tests Efficacy on symptoms will be explored by measuring changes in the Frontal Behavioral Inventory FBI the Aphasia Quotient AQ of the Western Aphasia Battery WAB the Mini Mental State Examination MMSE the Mattis Dementia Rating Scale MDRS the Frontal Assessment Battery FAB the Neuropsychiatric Inventory NPI the Alzheimers Disease Cooperative Study-Activities of Daily Living ADCS-ADL Scale the Clinical Global Impressions CGI Scales of Severity or Change and subscales of the WAB and FBI Changes in the results of neurologic examinations will also be documented
The descriptive analyses will be performed no hypotheses are specified for statistical testing Safety and efficacy assessments will be summarized Safety and Efficacy changes will be calculated from the screeningbaseline of the galantamine treatment period to Week 18 open label galantamine treatment period and Week 26 entire study for subjects randomized to galantamine for the 8 week withdrawal period Comparisons between the placebo and galantamine treatment groups will use the changes in safety and efficacy parameters from Weeks 18 to 26 the double blind placebo controlled randomized withdrawal period Using a flexible dosing regimen subjects will receive galantamine as oral tablets up to 8 or 12 mg twice per day for 18 weeks Subjects will then be randomly assigned 11 in a double blind fashion to galantamine at the same dose or to placebo for an additional 8 weeks of treatment
The expectation is that subjects who remain on galantamine for the additional 8 weeks will continue to improve or will remain stable with regard to their behavior language cognition and global function whereas subjects who are assigned to placebo will show a decline in some of these functions This approach will allow an assessment of the effects of galantamine treatment challenge and galantamine withdrawal de-challenge
This study will involve a maximum of 40 subjects with Pick ComplexFrontotemporal Dementia Subjects who meet the inclusion and exclusion criteria will receive galantamine 4 mg twice a day for 4 weeks followed by 8 mg twice a day for 4 weeks At 8 weeks the dose of galantamine will be maintained at 8 mg or increased to 12 mg twice a day based on tolerability At the end of 12 weeks the dose of galantamine will be maintained at 8 or 12 mg twice a day or reduced to 8 mg twice a day based on tolerability The dose will be fixed for the remainder of the open label treatment period Following 18 weeks of galantamine treatment subjects will be randomly assigned 11 to continued treatment with galantamine at the same dose or placebo for an additional 8 weeks Subjects and caregivers will be contacted by phone during the study and encouraged to contact the site at any time if they have concerns If the subjects symptoms appear to be substantially worsening and the investigator determines that the subject has deteriorated he will advise the subject and caregiver about possible early completion of the study early escape Subjects electing early escape will complete final efficacy and safety assessments then discontinue study medication Once they have completed the study they will begin the treatment of their choice in consultation with their physician Subjects will be seen for assessment at Visit 1 screening Visit 2 baseline Visits 3 and 4 12 and 18 weeks after the start of open label galantamine treatment and Visit 5 8 weeks after the start of the double blind withdrawal period or at early escape or upon premature discontinuation The subject and caregiver will return for an unscheduled visit if in the judgment of the investigator the subject requires clinical assessment between visits
Subject selection criteria will ensure inclusion of subjects who have a clinical diagnosis of Pick ComplexFrontotemporal Dementia established by published consensus criteria and supported by neuroradiologic confirmation The subjects selected for the study will have a diagnosis of primary progressive aphasia or frontotemporal dementia
Safety and tolerability will be monitored by assessment of adverse events electrocardiograms physical examinations blood pressure heart rate weight and laboratory tests Efficacy on symptoms will be explored by measuring changes in the Frontal Behavioral Inventory FBI the Aphasia Quotient AQ of the Western Aphasia Battery WAB the Mini Mental State Examination MMSE the Mattis Dementia Rating Scale MDRS the Frontal Assessment Battery FAB the Neuropsychiatric Inventory NPI the Alzheimers Disease Cooperative Study-Activities of Daily Living ADCS-ADL Scale the Clinical Global Impressions CGI Scales of Severity or Change and subscales of the WAB and FBI Changes in the results of neurologic examinations will also be documented
The descriptive analyses will be performed no hypotheses are specified for statistical testing Safety and efficacy assessments will be summarized Safety and Efficacy changes will be calculated from the screeningbaseline of the galantamine treatment period to Week 18 open label galantamine treatment period and Week 26 entire study for subjects randomized to galantamine for the 8 week withdrawal period Comparisons between the placebo and galantamine treatment groups will use the changes in safety and efficacy parameters from Weeks 18 to 26 the double blind placebo controlled randomized withdrawal period Using a flexible dosing regimen subjects will receive galantamine as oral tablets up to 8 or 12 mg twice per day for 18 weeks Subjects will then be randomly assigned 11 in a double blind fashion to galantamine at the same dose or to placebo for an additional 8 weeks of treatment
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