Alzheimer's Disease, Behavioral Variant Frontotemporal Dementia
Conditions
Keywords
Dementia, Alzheimer Disease, bvFTD, Frontotemporal Dementia, Neurodegenerative Diseases, Brain Diseases, Cognitive Disorders
Brief summary
The purpose of this study is to provide subjects who have completed participation in a Phase 2 or Phase 3 trial of LMTM continued access to therapy and to evaluate the long-term safety of LMTM.
Interventions
DRUGLMTM
The initial LMTM dose was 200 mg/day (one 100-mg tablet twice daily), except in subjects with bvFTD who were taking a reduced dose (i.e., 100 mg/day) upon entering this extension study. The dose could be increased (after at least 13 weeks of treatment) or decreased (at any time at or after 2 weeks of treatment) by the Investigator in 100-mg increments or decrements. The maximum allowable dose was 300 mg/day (or in those countries where limited by a Competent Authority or Ethics Committee, 200 mg/day).
Sponsors
TauRx Therapeutics Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Subjects with all cause dementia and probable Alzheimer's disease at enrollment and who completed participation in one of the following three TauRx studies (inclusive of the 4-week post-treatment follow-up visit): TRx-237-005, TRx-237-008, or TRx-237-015. * Subjects with a diagnosis of probable bvFTD at enrollment and who completed participation in TauRx study TRx-237-007 through Visit 9 (Week 52). * Females, if of child-bearing potential, must practice true abstinence or continue to use adequate contraception and agree to maintain this throughout the study * Subject, and/or, in the case of reduced decision-making capacity, legally acceptable representative(s) consistent with national law and ethics approval is/are able to read, understand, and provide written informed consent * Has an identified adult caregiver who is willing to provide written informed consent for his/her own participation; is able to read, understand, and speak the designated language at the study site; either lives with the subject or sees the subject for ≥1 hour/day ≥3 days/week; agrees to accompany the subject to each study visit; and is able to verify daily compliance with study drug * Able to comply with the study procedures
Exclusion criteria
* History of swallowing difficulties * Pregnant or breastfeeding * Clinically significant laboratory, pulse co-oximetry, electrocardiogram, or imaging abnormality (in originating study) or emergent intercurrent illness that, in the judgment of the principal investigator, could result in the risk of participation outweighing the potential benefit * Current participation in, or intent to enroll in, another clinical trial of a drug, biologic, device, or medical food * In Germany, subjects mandated to reside in a continuous care or assisted living facility or those whose willingness to participate in the clinical trial may be unduly influenced
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious or Non-serious Adverse Events | Up to 34 months | Study-emergent adverse events (including the onset of new adverse events or worsening of pre-existing adverse events) were recorded from the time of first dose in this study to the end of study participation. All laboratory test, vital sign, or electrocardiogram parameter abnormalities deemed clinically significant by the Investigator were to be reported as adverse events. |
Countries
Australia, Belgium, Canada, Croatia, Finland, France, Germany, Malaysia, Netherlands, Romania, Russia, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
Subjects who completed a Phase 2 or 3 study of LMTM were eligible to enroll, pending their ability to meet the inclusion/exclusion criteria. A total of 913 subjects enrolled; however, data for 16 subjects in Spain were later excluded (GCP issues) and 1 UK subject was never dosed. Thus, 896 subjects are included in all analyses except disposition.
Participants by arm
| Arm | Count |
|---|---|
| LMTM 100-300 mg/Day The initial LMTM dose was 200 mg/day (one 100-mg tablet twice daily), except in subjects with bvFTD who were taking a reduced dose (i.e., 100 mg/day) upon entering this extension study. The dose could be increased (after at least 13 weeks of treatment) or decreased (at any time at or after 2 weeks of treatment) by the Investigator in 100-mg increments or decrements. The maximum allowable dose was 300 mg/day (or in those countries where limited by a Competent Authority or Ethics Committee, 200 mg/day). | 896 |
| Total | 896 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 144 |
| Overall Study | Blue staining | 6 |
| Overall Study | Death | 9 |
| Overall Study | Intolerance/dosing issues/interruption | 5 |
| Overall Study | Lack of Efficacy | 98 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Missing (Site closure) | 16 |
| Overall Study | Non-compliance with study drug | 11 |
| Overall Study | Physician Decision | 14 |
| Overall Study | Study terminated by Sponsor | 346 |
| Overall Study | Withdrawal by Caregiver | 85 |
| Overall Study | Withdrawal by Legal Representative | 31 |
| Overall Study | Withdrawal by Subject | 77 |
| Overall Study | Worsening dementia/caregiver withdrawal | 6 |
Baseline characteristics
| Characteristic | LMTM 100-300 mg/Day |
|---|---|
| Age, Continuous | 69.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 864 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants |
| Race (NIH/OMB) Asian | 72 Participants |
| Race (NIH/OMB) Black or African American | 18 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Race (NIH/OMB) White | 783 Participants |
| Region of Enrollment Australia | 41 participants |
| Region of Enrollment Belgium | 12 participants |
| Region of Enrollment Canada | 51 participants |
| Region of Enrollment Croatia | 11 participants |
| Region of Enrollment Finland | 18 participants |
| Region of Enrollment France | 11 participants |
| Region of Enrollment Germany | 12 participants |
| Region of Enrollment Malaysia | 8 participants |
| Region of Enrollment Netherlands | 2 participants |
| Region of Enrollment Romania | 1 participants |
| Region of Enrollment Russia | 35 participants |
| Region of Enrollment Singapore | 22 participants |
| Region of Enrollment South Korea | 13 participants |
| Region of Enrollment Spain | 23 participants |
| Region of Enrollment Taiwan | 16 participants |
| Region of Enrollment United Kingdom | 161 participants |
| Region of Enrollment United States | 459 participants |
| Sex: Female, Male Female | 478 Participants |
| Sex: Female, Male Male | 418 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 896 |
| other Total, other adverse events | 717 / 896 |
| serious Total, serious adverse events | 146 / 896 |
Outcome results
Primary
Number of Participants With Serious or Non-serious Adverse Events
Study-emergent adverse events (including the onset of new adverse events or worsening of pre-existing adverse events) were recorded from the time of first dose in this study to the end of study participation. All laboratory test, vital sign, or electrocardiogram parameter abnormalities deemed clinically significant by the Investigator were to be reported as adverse events.
Time frame: Up to 34 months
Population: The safety population was composed of participants dosed with 100-300 mg LMTM who were used for analysis. Safety was assessed over time by means of adverse event and concomitant medication recording; clinical laboratory tests; vital sign measurements and weight; 12-lead electrocardiograms; and targeted physical and neurological examinations.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| LMTM 100-300 mg/Day | Number of Participants With Serious or Non-serious Adverse Events | 734 Participants |