Clinical Trials List
Protocol NumberRVT-101-3001
NCT Number(ClinicalTrials.gov Identfier)NCT02585934
2016-03-07 - 2017-12-31
Phase III
Terminated4
ICD-10F03.90
Unspecified dementia without behavioral disturbance
ICD-10G30
Alzheimer's disease
ICD-9331.0
Alzheimer's disease
A Phase 3, double-blind, randomized study of RVT-101 versus placebo when added to existing stable donepezil treatment in subjects with mild to moderate Alzheimer’s disease
-
Trial Applicant
WORLDWIDE CLINICAL TRIALS (TAIWAN) CO., LTD.
-
Sponsor
Axovant Sciences Ltd.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Kang-Hsu Lin Division of Neurology
- Jui-Cheng Chen Division of Neurology
- Chon-Haw Tsai Division of Neurology
- Yuh-Cherng Guo Division of Neurology
- Hui-Chun Huang Division of Neurology
- Ming-Kuei Lu Division of Neurology
- Kuan-Fei Chen Division of Neurology
- Yi-Ting Hsu Division of Neurology
- Wei-Shih Huang Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
CRO
Co-Principal Investigator
- KuoLun Huang Division of Neurology
- 郭弘明 Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- TA-FU CHEN Division of Neurology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Alzheimer’s disease
Objectives
This Phase 3 study seeks to confirm a demonstrated treatment effect of intepirdine (RVT-101) on both cognition and activities of daily living when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer's disease after 24 weeks of double-blind treatment. This study will also provide further information on the safety and tolerability of the 35-mg dose of intepirdine (RVT-101) when used in combination with donepezil compared to donepezil alone. This study is being conducted under the agreement of a Special Protocol Assessment by FDA. Subjects completing this study will be eligible to enroll in a 12 month open-label study of RVT-101 (RVT-101-3002) in which concomitant medications for the treatment of Alzheimer's disease including memantine will be allowed.
Primary
• To assess the effects of RVT-101 versus placebo as adjuncts to
stable donepezil therapy on cognitive function as measured by the
Alzheimer’s Disease Assessment Scale – Cognitive Subscale 11
items (ADAS-Cog-11) after 24 weeks of treatment
• To assess the effects of RVT-101 versus placebo as adjuncts to
stable donepezil therapy on activities of daily living as measured
by the Alzheimer’s Disease Cooperative Study - Activities of
Daily Living (ADCS-ADL) scale after 24 weeks of treatment
Test Drug
RVT-101
Active Ingredient
5-HT6 antagonist
Dosage Form
tablet
Dosage
35
Endpoints
Primary Outcome Measures :
1. Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24 [ Time Frame: Baseline, 24 weeks ]
The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment.
2. Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24 [ Time Frame: Baseline, 24 weeks ]
The ADCS-ADL scale measures functional impairment in terms of activities of daily living. The score ranges from 0 to 78. The lower the score, the greater the impairment; higher scores indicate better (more desirable) function
Secondary Outcome Measures :
1. Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24 [ Time Frame: 24 weeks ]
The CIBIC+ assessment measures the global functioning of the subject. The CIBIC+ is scored as a seven-point categorical rating, ranging from a score of 1 (indicating "very much improved"), to a score of 4 (indicating "no change"), or to a score of 7 (indicating "very much worse.") Lower CIBIC+ scores indicate better (more desirable) function
2. The Dependence Scale (DS) Score Change From Baseline to Week 24 [ Time Frame: Baseline, 24 weeks ]
The DS measures the amount of assistance patients with dementia require in performing daily activities. The scale consists of 13 items, representing a range of severity from mild to severe levels of dependency. The score range is from 0 to 15 with higher scores indicating greater dependency.
3. Neuropsychiatric Inventory (NPI) Score Change From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ]
The NPI is a behavior rating scale composed of a 12-item structured interview of the caregiver that is scored from 0 to 144 (the higher the score, the greater the psychiatric disturbance). It assesses 12 behavioral disturbances occurring in dementia patients: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor activity, night-time behavior disturbances, and eating disturbances. Both the frequency and the severity of each behavior are determined.
4. ADAS-Cog-13 Score Change From Baseline to Week 24 [ Time Frame: Baseline, 24 weeks ]
13-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 additional items: delayed word recall and total digit cancellation. Scores for the ADAS-Cog-13 range from 0 to 85 with higher scores indicating greater dysfunction.
5. Measurement of Concentrations of RVT-101 (Intepirdine) in Plasma [ Time Frame: Week 6, Week 12, Week 18, Week 24 ]
Measurement collected at timepoints Week 6, Week 12, Week 18, and Week 24
1. Alzheimer's Disease Assessment Scale - Cognitive Subscale 11 Items (ADAS-Cog-11) Score Change From Baseline to Week 24 [ Time Frame: Baseline, 24 weeks ]
The 11-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. The ADAS-Cog-11 total score range is from 0 to 70, with a higher score indicating more severe cognitive impairment.
2. Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Score Change From Baseline to Week 24 [ Time Frame: Baseline, 24 weeks ]
The ADCS-ADL scale measures functional impairment in terms of activities of daily living. The score ranges from 0 to 78. The lower the score, the greater the impairment; higher scores indicate better (more desirable) function
Secondary Outcome Measures :
1. Clinical Global Impression of Change - Plus Caregiver Interview (CIBIC+) Score at Week 24 [ Time Frame: 24 weeks ]
The CIBIC+ assessment measures the global functioning of the subject. The CIBIC+ is scored as a seven-point categorical rating, ranging from a score of 1 (indicating "very much improved"), to a score of 4 (indicating "no change"), or to a score of 7 (indicating "very much worse.") Lower CIBIC+ scores indicate better (more desirable) function
2. The Dependence Scale (DS) Score Change From Baseline to Week 24 [ Time Frame: Baseline, 24 weeks ]
The DS measures the amount of assistance patients with dementia require in performing daily activities. The scale consists of 13 items, representing a range of severity from mild to severe levels of dependency. The score range is from 0 to 15 with higher scores indicating greater dependency.
3. Neuropsychiatric Inventory (NPI) Score Change From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ]
The NPI is a behavior rating scale composed of a 12-item structured interview of the caregiver that is scored from 0 to 144 (the higher the score, the greater the psychiatric disturbance). It assesses 12 behavioral disturbances occurring in dementia patients: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor activity, night-time behavior disturbances, and eating disturbances. Both the frequency and the severity of each behavior are determined.
4. ADAS-Cog-13 Score Change From Baseline to Week 24 [ Time Frame: Baseline, 24 weeks ]
13-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 additional items: delayed word recall and total digit cancellation. Scores for the ADAS-Cog-13 range from 0 to 85 with higher scores indicating greater dysfunction.
5. Measurement of Concentrations of RVT-101 (Intepirdine) in Plasma [ Time Frame: Week 6, Week 12, Week 18, Week 24 ]
Measurement collected at timepoints Week 6, Week 12, Week 18, and Week 24
Inclution Criteria
Inclusion Criteria
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Male or female subject with a clinical diagnosis of AD in accordance the recommendations
from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic
guidelines for AD (McKhann et al, 2011).
2. Subject has a documented history of at least 4 months of ongoing donepezil therapy for AD,
with stable dosing of 5 or 10 mg/day for at least the last 2 months and with no intent to
change for the duration of the study.
3. Subject has an MMSE score 12 to 24 inclusive at Screening and a Baseline MMSE score
10 to 26 inclusive. The difference between the Screening and Baseline MMSE score is less
than or equal to 3 points. If a greater than 3-point difference between the Screening and
Baseline MMSE score is in the opinion of the investigator due to recent changes in AD
medication, Screening may be extended for an additional 3 weeks after discussion with the
Medical Monitor, during which time MMSE stability, defined as less than or equal to
3-point change over 3 weeks, must be observed.
4. Subject has a Hachinski Ischaemia score less than or equal to 4 at Screening.
5. Magnetic resonance imaging (MRI) or computed tomography (CT) scan performed within
12 months before screening with findings consistent with the diagnosis of dementia due to
AD without any other clinically significant pathologies. If an MRI (preferred) or CT scan is
unavailable or was performed longer than 12 months prior to Screening, one must be
performed during the Screening Period (prior to Run-In).
6. Age greater than or equal to 50 years to less than or equal to 85 years at the time of
Screening.
7. If female, subject must be:
a. Of non-childbearing potential (i.e., any female who is post-menopausal [greater than
1 year without menstrual period in the absence of hormone replacement therapy]) or
surgically sterile; or,
b. If pre-menopausal or menopausal for 1 year or less, must have a negative pregnancy test
and must not be lactating at the Screening and Baseline Visits. Female subjects of
childbearing potential and who are sexually active are required to practice adequate
methods of birth control. Female subjects for whom menopausal status is in doubt in the
opinion of the investigator will be required to use an adequate form of birth control.
Acceptable, adequate form of birth control is defined as consistent use of combined
effective methods of contraception including at least 1 barrier method.
Male subjects who are sexually active will also be required to use an adequate form of birth
control as described above.
8. Subject has the ability to comply with procedures for cognitive and other testing in the
opinion of the investigator.
9. Subject must be able to ingest pills (in tablet form) whole.
10. Subject lives with (or has substantial periods of contact with) a regular caregiver who is
willing to attend visits, oversee the subject’s compliance with protocol-specified procedures
and study medication, and report on subject’s status, and who has substantial contact with
the subject. If the caregiver does not cohabitate with the subject, he/she ideally should have
a minimum of 10 hours total and at least 3 days contact with the subject per week. Prior to
randomization, study representatives will review eligibility of non-cohabitating caregivers.
Every effort should be made to have the same caregiver throughout the study.
11. Subject has provided full written informed consent prior to the performance of any
protocol-specified procedure; or if unable to provide informed consent due to cognitive
status, subject has provided assent and a legally acceptable representative has provided full
written informed consent on behalf of the subject.
12. Caregiver has provided full written informed consent on his/her own behalf prior to the
performance of any protocol-specified procedure.
13. General health status is acceptable for participation in a 24-week study.
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Male or female subject with a clinical diagnosis of AD in accordance the recommendations
from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic
guidelines for AD (McKhann et al, 2011).
2. Subject has a documented history of at least 4 months of ongoing donepezil therapy for AD,
with stable dosing of 5 or 10 mg/day for at least the last 2 months and with no intent to
change for the duration of the study.
3. Subject has an MMSE score 12 to 24 inclusive at Screening and a Baseline MMSE score
10 to 26 inclusive. The difference between the Screening and Baseline MMSE score is less
than or equal to 3 points. If a greater than 3-point difference between the Screening and
Baseline MMSE score is in the opinion of the investigator due to recent changes in AD
medication, Screening may be extended for an additional 3 weeks after discussion with the
Medical Monitor, during which time MMSE stability, defined as less than or equal to
3-point change over 3 weeks, must be observed.
4. Subject has a Hachinski Ischaemia score less than or equal to 4 at Screening.
5. Magnetic resonance imaging (MRI) or computed tomography (CT) scan performed within
12 months before screening with findings consistent with the diagnosis of dementia due to
AD without any other clinically significant pathologies. If an MRI (preferred) or CT scan is
unavailable or was performed longer than 12 months prior to Screening, one must be
performed during the Screening Period (prior to Run-In).
6. Age greater than or equal to 50 years to less than or equal to 85 years at the time of
Screening.
7. If female, subject must be:
a. Of non-childbearing potential (i.e., any female who is post-menopausal [greater than
1 year without menstrual period in the absence of hormone replacement therapy]) or
surgically sterile; or,
b. If pre-menopausal or menopausal for 1 year or less, must have a negative pregnancy test
and must not be lactating at the Screening and Baseline Visits. Female subjects of
childbearing potential and who are sexually active are required to practice adequate
methods of birth control. Female subjects for whom menopausal status is in doubt in the
opinion of the investigator will be required to use an adequate form of birth control.
Acceptable, adequate form of birth control is defined as consistent use of combined
effective methods of contraception including at least 1 barrier method.
Male subjects who are sexually active will also be required to use an adequate form of birth
control as described above.
8. Subject has the ability to comply with procedures for cognitive and other testing in the
opinion of the investigator.
9. Subject must be able to ingest pills (in tablet form) whole.
10. Subject lives with (or has substantial periods of contact with) a regular caregiver who is
willing to attend visits, oversee the subject’s compliance with protocol-specified procedures
and study medication, and report on subject’s status, and who has substantial contact with
the subject. If the caregiver does not cohabitate with the subject, he/she ideally should have
a minimum of 10 hours total and at least 3 days contact with the subject per week. Prior to
randomization, study representatives will review eligibility of non-cohabitating caregivers.
Every effort should be made to have the same caregiver throughout the study.
11. Subject has provided full written informed consent prior to the performance of any
protocol-specified procedure; or if unable to provide informed consent due to cognitive
status, subject has provided assent and a legally acceptable representative has provided full
written informed consent on behalf of the subject.
12. Caregiver has provided full written informed consent on his/her own behalf prior to the
performance of any protocol-specified procedure.
13. General health status is acceptable for participation in a 24-week study.
Exclusion Criteria
Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Other Causes for Dementia
1. Diagnosis of possible, probable, or definite vascular dementia in accordance with National
Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche
l’Enseignement en Neurosciences criteria.
2. History and/or evidence (including CT or MRI scan performed within the past 12 months or
at Screening) of any other CNS disorder that could be interpreted as a cause of dementia (in
the opinion of the investigator), e.g., cerebrovascular disease (transient ischemic attack,
stroke, hemorrhage); structural or developmental abnormality; epilepsy; infectious,
degenerative, or inflammatory/demyelinating CNS conditions; or Parkinson’s disease.
3. Evidence of the following disorders where this is thought to be the cause of, or to contribute
to the severity of, the subject’s dementia: current vitamin B12 deficiency, hypothyroidism,
neurosyphilis, or Wernicke’s encephalopathy.
4. Focal findings on the neurological exam (excluding changes attributable to peripheral
injury) that are inconsistent with a primary diagnosis of AD.
5. History of existing negative amyloid positron emission tomography scan or similar brain
amyloid imaging, or Screen Failure from research trial due to negative amyloid imaging
within 5 years. Note: amyloid scan is not required for participation in this study.
6. Atypical clinical features or clinical course of dementia that would lead the investigator to
conclude symptoms are more likely due to an alternate dementia diagnosis including, but not
limited to, frontotemporal dementia, Lewy body dementia, or others.
Confounding Medical Conditions
7. History of significant psychiatric illness such as schizophrenia or bipolar affective disorder
or any other significant psychiatric illness that in the opinion of the investigator would
interfere with participation in the study; history of major depressive disorder in the past year,
or current major depressive episode.
8. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the
C-SSRS within the past year, at Screening or at Baseline; (2) suicidal behaviors within the
past year; (3) clinical assessment of significant suicidal risk during subject interview.
9. Current psychosis that in the opinion of the investigator would interfere with the subject’s
ability to participate in this study.
10. History of epilepsy or unexplained seizure in the past 5 years, unexplained recent loss of
consciousness, or history of significant head trauma with loss of consciousness.
11. History of malignancy during the 5 years before Screening. History of basal cell carcinoma
and melanoma in situ are permitted. History of other cancers currently in a non-active state
may be acceptable after review with the Medical Monitor.
12. Any clinically relevant concomitant disease including progressive liver or kidney
dysfunction, history of myocardial infarction or unstable angina within 6 months of
Screening, history of more than 1 myocardial infarction within 5 years of Screening, history
of clinically significant stroke, or any other medical or psychiatric condition, which, in the
opinion of the investigator, makes the subject unsuitable for inclusion in the study.
13. History of alcohol use disorder or other substance abuse disorder (excluding tobacco use),
according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria
in the past 10 years.
14. History of Down syndrome or mental retardation.
Concomitant Medications
15. Participation in another investigational drug or device study in AD during the 60 days prior
to the Screening Visit (Visit 1), or within 5 half-lives of use of the investigational drug prior
to the Screening Visit, whichever is longer. In addition, subjects who were previously
screened for another study in AD but failed the entry criteria for that study may be screened
with no time delay prior to the Screening Visit, provided that, in the opinion of the
investigator, and after review with the Medical Monitor, there is a realistic possibility that
the subject would be eligible. However, Screen Failures due to negative amyloid imaging
within 5 years will not be eligible for enrollment (see exclusion criterion 5).
16. Treatment with any concomitant medications as detailed in Table 1. Memantine and other
treatments for dementia including AChEIs other than donepezil must have been
discontinued 30 days prior to entry into the Single-Blind Run-In Period. Other prohibited
medications as outlined in Table 1, unless otherwise specified, need to have been
discontinued for 5 half-lives prior to screening and assessed as no longer clinically necessary
for the subject. Subjects taking memantine or other agents to treat cognitive impairment
associated with AD at the time of Screening will be considered Screen Failures. However,
subjects with recent discontinuation prior to Screening of memantine or other agents to treat
cognitive impairment who will have been discontinued for 30 days prior to the Single-Blind
Run-In Period may continue. Subjects who screen fail may be rescreened once (see
Section 6.5).
Unacceptable Test/Laboratory Values
17. Postural hypotension (fall in systolic blood pressure of greater than 30 mmHg or fall in
diastolic blood pressure of greater than 20 mmHg on standing compared to sitting) at the
time of screening. Subjects who present at the time of screening with postural hypotension
yet have no known history of postural hypotension, nor underlying medical condition related
to hypotension, may be rescreened.
18. Persistent or recurrent liver enzyme elevations, alanine transaminase (ALT) and/or aspartate
aminotransferase (AST) greater than or equal to 2.0 times upper limit of normal (ULN).
19. Total bilirubin over 1.5 x ULN except due to documented Gilbert’s disease.
20. Calculated creatinine clearance less than 40 mL/min (Cockroft-Gault formula):
Adult males: [(140 – age in years) × (weight in kg)] ÷ 72 × serum creatinine*
Adult females: 0.85 × [((140 – age in years) × (weight in kg)) ÷ 72 × serum creatinine*]
* in mg/dL
21. Positive hepatitis B surface antigen or hepatitis C antibody test.
22. Confirmed corrected QT interval (QTc) value greater than or equal to 450 msec for males or
greater than or equal to 470 msec for females. Subjects with a QRS value greater than
120 msec and QTc value less than 500 msec may be eligible following discussion with the
Medical Monitor.
Other
23. Previous exposure to RVT-101 or SB742457.
24. Subject is unable to take study medication as prescribed throughout the study (with
assistance is acceptable), has a significant history of non-compliance with prescribed
medication, or is at risk of non-compliance with study medication or procedures.
25. Subject or caregiver is an immediate family member or employee of the participating
investigator, any of the participating site staff, or of the sponsor study staff.
26. Subject was prescribed cognitive tasks for cognitive rehabilitation performed under medical
supervision in the 3 months prior to Screening and/or during the study.
27. Subject has participated in a program of neurostimulation in the past 3 months or plans to
participate in a program of neurostimulation during the course of the study
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
Other Causes for Dementia
1. Diagnosis of possible, probable, or definite vascular dementia in accordance with National
Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche
l’Enseignement en Neurosciences criteria.
2. History and/or evidence (including CT or MRI scan performed within the past 12 months or
at Screening) of any other CNS disorder that could be interpreted as a cause of dementia (in
the opinion of the investigator), e.g., cerebrovascular disease (transient ischemic attack,
stroke, hemorrhage); structural or developmental abnormality; epilepsy; infectious,
degenerative, or inflammatory/demyelinating CNS conditions; or Parkinson’s disease.
3. Evidence of the following disorders where this is thought to be the cause of, or to contribute
to the severity of, the subject’s dementia: current vitamin B12 deficiency, hypothyroidism,
neurosyphilis, or Wernicke’s encephalopathy.
4. Focal findings on the neurological exam (excluding changes attributable to peripheral
injury) that are inconsistent with a primary diagnosis of AD.
5. History of existing negative amyloid positron emission tomography scan or similar brain
amyloid imaging, or Screen Failure from research trial due to negative amyloid imaging
within 5 years. Note: amyloid scan is not required for participation in this study.
6. Atypical clinical features or clinical course of dementia that would lead the investigator to
conclude symptoms are more likely due to an alternate dementia diagnosis including, but not
limited to, frontotemporal dementia, Lewy body dementia, or others.
Confounding Medical Conditions
7. History of significant psychiatric illness such as schizophrenia or bipolar affective disorder
or any other significant psychiatric illness that in the opinion of the investigator would
interfere with participation in the study; history of major depressive disorder in the past year,
or current major depressive episode.
8. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the
C-SSRS within the past year, at Screening or at Baseline; (2) suicidal behaviors within the
past year; (3) clinical assessment of significant suicidal risk during subject interview.
9. Current psychosis that in the opinion of the investigator would interfere with the subject’s
ability to participate in this study.
10. History of epilepsy or unexplained seizure in the past 5 years, unexplained recent loss of
consciousness, or history of significant head trauma with loss of consciousness.
11. History of malignancy during the 5 years before Screening. History of basal cell carcinoma
and melanoma in situ are permitted. History of other cancers currently in a non-active state
may be acceptable after review with the Medical Monitor.
12. Any clinically relevant concomitant disease including progressive liver or kidney
dysfunction, history of myocardial infarction or unstable angina within 6 months of
Screening, history of more than 1 myocardial infarction within 5 years of Screening, history
of clinically significant stroke, or any other medical or psychiatric condition, which, in the
opinion of the investigator, makes the subject unsuitable for inclusion in the study.
13. History of alcohol use disorder or other substance abuse disorder (excluding tobacco use),
according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria
in the past 10 years.
14. History of Down syndrome or mental retardation.
Concomitant Medications
15. Participation in another investigational drug or device study in AD during the 60 days prior
to the Screening Visit (Visit 1), or within 5 half-lives of use of the investigational drug prior
to the Screening Visit, whichever is longer. In addition, subjects who were previously
screened for another study in AD but failed the entry criteria for that study may be screened
with no time delay prior to the Screening Visit, provided that, in the opinion of the
investigator, and after review with the Medical Monitor, there is a realistic possibility that
the subject would be eligible. However, Screen Failures due to negative amyloid imaging
within 5 years will not be eligible for enrollment (see exclusion criterion 5).
16. Treatment with any concomitant medications as detailed in Table 1. Memantine and other
treatments for dementia including AChEIs other than donepezil must have been
discontinued 30 days prior to entry into the Single-Blind Run-In Period. Other prohibited
medications as outlined in Table 1, unless otherwise specified, need to have been
discontinued for 5 half-lives prior to screening and assessed as no longer clinically necessary
for the subject. Subjects taking memantine or other agents to treat cognitive impairment
associated with AD at the time of Screening will be considered Screen Failures. However,
subjects with recent discontinuation prior to Screening of memantine or other agents to treat
cognitive impairment who will have been discontinued for 30 days prior to the Single-Blind
Run-In Period may continue. Subjects who screen fail may be rescreened once (see
Section 6.5).
Unacceptable Test/Laboratory Values
17. Postural hypotension (fall in systolic blood pressure of greater than 30 mmHg or fall in
diastolic blood pressure of greater than 20 mmHg on standing compared to sitting) at the
time of screening. Subjects who present at the time of screening with postural hypotension
yet have no known history of postural hypotension, nor underlying medical condition related
to hypotension, may be rescreened.
18. Persistent or recurrent liver enzyme elevations, alanine transaminase (ALT) and/or aspartate
aminotransferase (AST) greater than or equal to 2.0 times upper limit of normal (ULN).
19. Total bilirubin over 1.5 x ULN except due to documented Gilbert’s disease.
20. Calculated creatinine clearance less than 40 mL/min (Cockroft-Gault formula):
Adult males: [(140 – age in years) × (weight in kg)] ÷ 72 × serum creatinine*
Adult females: 0.85 × [((140 – age in years) × (weight in kg)) ÷ 72 × serum creatinine*]
* in mg/dL
21. Positive hepatitis B surface antigen or hepatitis C antibody test.
22. Confirmed corrected QT interval (QTc) value greater than or equal to 450 msec for males or
greater than or equal to 470 msec for females. Subjects with a QRS value greater than
120 msec and QTc value less than 500 msec may be eligible following discussion with the
Medical Monitor.
Other
23. Previous exposure to RVT-101 or SB742457.
24. Subject is unable to take study medication as prescribed throughout the study (with
assistance is acceptable), has a significant history of non-compliance with prescribed
medication, or is at risk of non-compliance with study medication or procedures.
25. Subject or caregiver is an immediate family member or employee of the participating
investigator, any of the participating site staff, or of the sponsor study staff.
26. Subject was prescribed cognitive tasks for cognitive rehabilitation performed under medical
supervision in the 3 months prior to Screening and/or during the study.
27. Subject has participated in a program of neurostimulation in the past 3 months or plans to
participate in a program of neurostimulation during the course of the study
The Estimated Number of Participants
-
Taiwan
40 participants
-
Global
1150 participants
