Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, Alzheimer's
Brief summary
The primary objective is to evaluate the efficacy of T-817MA as measured by ADAS-cog and ADCS-CGIC. The secondary objectives are: * To evaluate the safety and tolerability of T-817MA measured by clinical safety laboratories, physical examinations, ECGs and solicitation of adverse events. * To evaluate the efficacy of T-817MA as measured by ADCS-ADL, FAQ, Neuropsychiatric Inventory (NPI) and Mini-mental State Examination (MMSE).
Interventions
DRUGT-817MA-H
224 mg or 448 mg T-817 MA once daily
DRUGT-817MA-L
224 mg T-817 MA once daily
DRUGPlacebo
Placebo
Sponsors
Alzheimer's Disease Cooperative Study (ADCS)
FUJIFILM Toyama Chemical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Male or female (post-menopausal or surgically sterile) * Patients with Mild to moderate Alzheimer's disease who are receiving donepezil (Aricept®) or rivastigmine transdermal system (Exelon® Patch), . Memantine (Namenda®) is allowed only when prescribed in combination with donepezil or rivastigmine transdermal system. * Age 55 to 85 inclusive * Patients must be living in the community * Patients must have an eligible informant or study partner (caregiver) * Patients and eligible informant or study partner (caregiver) must be able to read and understand English. * Informed consent obtained from both the patient and the caregiver
Exclusion criteria
* Patients with clinically significant cardiac, hepatic or renal impairment * Patient have a dementia not of the Alzheimer's type etc (According to the protocol) * Patients who are taking any drug other than donepezil or rivastigmine transdermal system for Alzheimer's disease, including olal rivastigmine (Exelon®), galantamine (Razadyne®)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ADAS-cog Change From Baseline to Week 52 | Baseline and 52 weeks | The ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) is a structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions are also obtained. The test is scored in terms of errors, with higher scores reflecting poorer performance and greater impairment. Scores can range from 0 (best) to 70 (worse). |
| CGIC | 52 weeks | The ADCS-CGIC (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change) is a validated categorical measure of change in the patient's clinical condition between baseline and follow-up visits. It measures whether the effects of active treatment are substantial enough to be detected by a skilled and experienced clinician on the basis of a clinical interview and examination. It relies on both direct examination of the patient and an interview of the study partner. A skilled and experienced clinician who is blinded to treatment assignment rates the patient on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening). It is suggested that the instrument has distinct clinical utility in assessing change in AD clinical trials. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ADCS-ADL Change From Baseline to Week 52 | Baseline and 52 weeks | The ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) is a validated tool for assessing instrumental and basic activities of daily living based on a 23-item structured interview of the study partner. The scale has a range of 0 to 78, with lower scores indicating greater impairment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| T-817MA-H 224 mg T-817MA once daily for first 4 weeks and 448 mg T-817MA once daily for the following weeks.
T-817MA-H: 224 mg or 448 mg T-817 MA once daily | 154 |
| T-817MA-L 224 mg T-817MA once daily
T-817MA-L: 224 mg T-817 MA once daily | 159 |
| Placebo Placebo once daily
Placebo: Placebo | 156 |
| Total | 469 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 23 | 23 | 7 |
| Overall Study | Death | 2 | 2 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Relocation etc. | 2 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 9 | 17 | 4 |
Baseline characteristics
| Characteristic | T-817MA-L | Placebo | Total | T-817MA-H |
|---|---|---|---|---|
| Age, Continuous | 71.9 years STANDARD_DEVIATION 8.2 | 71.8 years STANDARD_DEVIATION 7.5 | 71.9 years STANDARD_DEVIATION 7.8 | 71.8 years STANDARD_DEVIATION 7.8 |
| ApoE4 genotype Heterozygotes | 74 Participants | 71 Participants | 200 Participants | 55 Participants |
| ApoE4 genotype Homozygotes | 21 Participants | 27 Participants | 80 Participants | 32 Participants |
| ApoE4 genotype Non-carriers | 57 Participants | 50 Participants | 161 Participants | 54 Participants |
| ApoE4 genotype Unknown | 7 Participants | 8 Participants | 28 Participants | 13 Participants |
| MMSE | 18.2 units on a scale STANDARD_DEVIATION 3.8 | 18.2 units on a scale STANDARD_DEVIATION 3.8 | 18.3 units on a scale STANDARD_DEVIATION 3.8 | 18.4 units on a scale STANDARD_DEVIATION 3.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 11 Participants | 26 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) White | 146 Participants | 142 Participants | 428 Participants | 140 Participants |
| Sex: Female, Male Female | 81 Participants | 89 Participants | 252 Participants | 82 Participants |
| Sex: Female, Male Male | 78 Participants | 67 Participants | 217 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 158 | 2 / 166 | 0 / 158 |
| other Total, other adverse events | 132 / 158 | 133 / 166 | 119 / 158 |
| serious Total, serious adverse events | 26 / 158 | 25 / 166 | 20 / 158 |
Outcome results
Primary
ADAS-cog Change From Baseline to Week 52
The ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) is a structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions are also obtained. The test is scored in terms of errors, with higher scores reflecting poorer performance and greater impairment. Scores can range from 0 (best) to 70 (worse).
Time frame: Baseline and 52 weeks
Population: The overall number of participants display the numbers of patients who were included in the mITT population and had baseline and at least one post-baseline ADAS-cog evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| T-817MA-H | ADAS-cog Change From Baseline to Week 52 | 7.08 units on a scale | Standard Error 0.756 |
| T-817MA-L | ADAS-cog Change From Baseline to Week 52 | 7.45 units on a scale | Standard Error 0.756 |
| Placebo | ADAS-cog Change From Baseline to Week 52 | 7.91 units on a scale | Standard Error 0.727 |
p-value: 0.3919Mixed Models Analysis
Primary
CGIC
The ADCS-CGIC (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change) is a validated categorical measure of change in the patient's clinical condition between baseline and follow-up visits. It measures whether the effects of active treatment are substantial enough to be detected by a skilled and experienced clinician on the basis of a clinical interview and examination. It relies on both direct examination of the patient and an interview of the study partner. A skilled and experienced clinician who is blinded to treatment assignment rates the patient on a 7-point Likert scale, ranging from 1 (marked improvement) to 7 (marked worsening). It is suggested that the instrument has distinct clinical utility in assessing change in AD clinical trials.
Time frame: 52 weeks
Population: The overall number of participants display the numbers of patients who were included in the mITT population and had at least one post-baseline CGIC evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| T-817MA-H | CGIC | 5.25 units on a scale | Standard Error 0.1 |
| T-817MA-L | CGIC | 5.24 units on a scale | Standard Error 0.1 |
| Placebo | CGIC | 5.22 units on a scale | Standard Error 0.1 |
p-value: 0.7588Mixed Models Analysis
Secondary
ADCS-ADL Change From Baseline to Week 52
The ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) is a validated tool for assessing instrumental and basic activities of daily living based on a 23-item structured interview of the study partner. The scale has a range of 0 to 78, with lower scores indicating greater impairment.
Time frame: Baseline and 52 weeks
Population: The overall number of participants display the numbers of patients who were included in the mITT population and had baseline and at least one post-baseline ADCS-ADL evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| T-817MA-H | ADCS-ADL Change From Baseline to Week 52 | -10.01 units on a scale | Standard Error 0.991 |
| T-817MA-L | ADCS-ADL Change From Baseline to Week 52 | -11.07 units on a scale | Standard Error 0.992 |
| Placebo | ADCS-ADL Change From Baseline to Week 52 | -11.29 units on a scale | Standard Error 0.957 |
p-value: 0.3212Mixed Models Analysis