Trial Outcomes & Findings for Bexarotene Amyloid Treatment for Alzheimer's Disease (NCT NCT01782742)
NCT ID: NCT01782742
Last Updated: 2016-02-12
Results Overview
The primary study endpoint for all subjects is the change from baseline to Week 4 in amyloid burden as measured by standard uptake units regional (SUVr) on amyloid brain imaging obtained through 18F-AV-45 PET
COMPLETED
PHASE2
20 participants
Baseline to Week 4
2016-02-12
Participant Flow
Recruitment was conducted in the United States at one site. The first participant was enrolled in April 2013.
49 participants were screened, 29 were screen failures, 20 participants were randomized to treatment. 1 was withdrawn after Week 4 treatment. Inclusion and exclusion criteria was the strict basis for eligibility.
Participant milestones
| Measure |
Bexarotene Treatment Arm
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Double-blind Treatment Phase
STARTED
|
16
|
4
|
|
Double-blind Treatment Phase
COMPLETED
|
15
|
4
|
|
Double-blind Treatment Phase
NOT COMPLETED
|
1
|
0
|
|
Open Label Phase
STARTED
|
19
|
0
|
|
Open Label Phase
COMPLETED
|
19
|
0
|
|
Open Label Phase
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Bexarotene Treatment Arm
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Double-blind Treatment Phase
Adverse Event
|
1
|
0
|
Baseline Characteristics
Bexarotene Amyloid Treatment for Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Bexarotene Treatment Arm
n=16 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Age at Screening
|
74.9 years
STANDARD_DEVIATION 6.6 • n=5 Participants
|
78.1 years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
75.5 years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race - Caucasian
|
15 participants
n=5 Participants
|
4 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race - African American
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Years of Education
|
14.7 years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
12.3 years
STANDARD_DEVIATION 3.3 • n=7 Participants
|
14.2 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
|
Years of Cognitive Symptoms
|
4.6 years
STANDARD_DEVIATION 1.9 • n=5 Participants
|
2.8 years
STANDARD_DEVIATION 0.96 • n=7 Participants
|
4.3 years
STANDARD_DEVIATION 1.9 • n=5 Participants
|
|
MMSE total score
|
13.7 units on a scale
n=5 Participants
|
17.0 units on a scale
n=7 Participants
|
14.4 units on a scale
n=5 Participants
|
|
ADAS-Cog score
|
49.9 units on a scale
n=5 Participants
|
40.3 units on a scale
n=7 Participants
|
48.0 units on a scale
n=5 Participants
|
|
CDR score
|
1.4 units on a scale
n=5 Participants
|
1.1 units on a scale
n=7 Participants
|
1.4 units on a scale
n=5 Participants
|
|
NPI score
|
8.7 units on a scale
n=5 Participants
|
7.0 units on a scale
n=7 Participants
|
8.4 units on a scale
n=5 Participants
|
|
NPI Distress Score
|
6.5 units on a scale
n=5 Participants
|
4.3 units on a scale
n=7 Participants
|
6.1 units on a scale
n=5 Participants
|
|
ADCS-ADL score
|
53.7 units on a scale
n=5 Participants
|
64.5 units on a scale
n=7 Participants
|
55.9 units on a scale
n=5 Participants
|
|
ApoE4 Status
Non-carriers
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
ApoE4 Status
Heterozygotes
|
6 participants
n=5 Participants
|
1 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
ApoE4 Status
Homozygotes
|
6 participants
n=5 Participants
|
0 participants
n=7 Participants
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 4The primary study endpoint for all subjects is the change from baseline to Week 4 in amyloid burden as measured by standard uptake units regional (SUVr) on amyloid brain imaging obtained through 18F-AV-45 PET
Outcome measures
| Measure |
Bexarotene
n=16 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Drug-Placebo Difference in Change From Baseline to Week 4 in the Composite Amyloid Burden of the Brain
|
-0.03 SUVr
Interval -0.06 to 0.01
|
0.02 SUVr
Interval -0.05 to 0.1
|
PRIMARY outcome
Timeframe: Baseline to Week 4Population: Change om composite and regional Beta Amyloid burden according to ApoE genotype on ALL SUBJECTS
This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (E-4 carriers compared to E-4 non-carriers)
Outcome measures
| Measure |
Bexarotene
n=16 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Primary Outcome by Genotype (ALL SUBJECTS)
Frontal Medial Orbital
|
-0.043 SUVr
Interval -0.081 to -0.006
|
-0.021 SUVr
Interval -0.096 to 0.054
|
|
Primary Outcome by Genotype (ALL SUBJECTS)
Anterior Cingulate
|
-0.040 SUVr
Interval -0.08 to 0.0
|
0.018 SUVr
Interval -0.061 to 0.098
|
|
Primary Outcome by Genotype (ALL SUBJECTS)
Parietal
|
-0.003 SUVr
Interval -0.034 to 0.027
|
0.044 SUVr
Interval -0.018 to 0.105
|
|
Primary Outcome by Genotype (ALL SUBJECTS)
Posterior Cingulate
|
-0.017 SUVr
Interval -0.065 to 0.031
|
0.044 SUVr
Interval -0.052 to 0.141
|
|
Primary Outcome by Genotype (ALL SUBJECTS)
Precuneus
|
-0.027 SUVr
Interval -0.069 to 0.014
|
0.040 SUVr
Interval -0.043 to 0.122
|
|
Primary Outcome by Genotype (ALL SUBJECTS)
Temporal
|
-0.038 SUVr
Interval -0.075 to 0.0
|
0.016 SUVr
Interval -0.059 to 0.09
|
PRIMARY outcome
Timeframe: Baseline to Week 4Population: Change in composite and regional Beta Amyloid Burden on non-ApoE4 carriers
Measures changes from baseline on treatment compared to placebo at week 4 on composite and regional Beta Amyloid burden according to ApoE genotype (NON ApoE4 CARRIERS)
Outcome measures
| Measure |
Bexarotene
n=4 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=3 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Composite
|
-0.097 SUVr
Interval -0.155 to -0.04
|
0.047 SUVr
Interval -0.019 to 0.114
|
|
Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Frontal Medial Orbital
|
-0.076 SUVr
Interval -0.146 to -0.007
|
0.005 SUVr
Interval -0.075 to 0.085
|
|
Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Anterior Cingulate
|
-0.096 SUVr
Interval -0.166 to -0.026
|
0.048 SUVr
Interval -0.034 to 0.129
|
|
Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Parietal
|
-0.068 SUVr
Interval -0.107 to -0.029
|
0.065 SUVr
Interval 0.02 to 0.11
|
|
Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Posterior Cingulate
|
-0.113 SUVr
Interval -0.18 to -0.046
|
0.074 SUVr
Interval -0.004 to 0.151
|
|
Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Precuneus
|
-0.127 SUVr
Interval -0.188 to -0.066
|
0.062 SUVr
Interval -0.008 to 0.132
|
|
Primary Outcome by Genotype (NON ApoE4 CARRIERS)
Temporal
|
-0.104 SUVr
Interval -0.162 to -0.045
|
0.031 SUVr
Interval -0.037 to 0.098
|
PRIMARY outcome
Timeframe: Baseline to Week 4Population: Change in composite and regional Beta Amyloid burden on ApoE4 carriers
This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (E-4 carriers)
Outcome measures
| Measure |
Bexarotene
n=12 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=1 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Primary Outcome by Genotype (ApoE4 CARRIERS)
Temporal
|
-0.015 SUVr
Interval -0.055 to 0.024
|
-0.030 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (ApoE4 CARRIERS)
Composite
|
-0.005 SUVr
Interval -0.041 to 0.031
|
-0.048 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (ApoE4 CARRIERS)
Frontal Medial Orbital
|
-0.033 SUVr
Interval -0.074 to 0.009
|
-0.099 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (ApoE4 CARRIERS)
Anterior Cingulate
|
-0.022 SUVr
Interval -0.062 to 0.019
|
-0.069 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (ApoE4 CARRIERS)
Parietal
|
0.018 SUVr
Interval -0.013 to 0.05
|
-0.019 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (ApoE4 CARRIERS)
Posterior Cingulate
|
0.015 SUVr
Interval -0.035 to 0.065
|
-0.044 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (ApoE4 CARRIERS)
Precuneus
|
0.006 SUVr
Interval -0.031 to 0.043
|
-0.027 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
PRIMARY outcome
Timeframe: Baseline to Week 4Population: Change in composite and regional Beta Amyloid burden on Heterozygote ApoE4 carriers
This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (HETEROZYGOTE ApoE4 CARRIERS)
Outcome measures
| Measure |
Bexarotene
n=6 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=1 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
Composite
|
-0.015 SUVr
Interval -0.037 to 0.008
|
-0.048 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
Frontal Medial Orbital
|
-0.061 SUVr
Interval -0.09 to -0.033
|
-0.099 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
Anterior Cingulate
|
-0.048 SUVr
Interval -0.08 to -0.016
|
-0.069 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
Parietal
|
0.034 SUVr
Interval 0.009 to 0.058
|
-0.019 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
Posterior Cingulate
|
-0.007 SUVr
Interval -0.035 to 0.022
|
-0.044 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
Precuneus
|
0.005 SUVr
Interval -0.021 to 0.032
|
-0.027 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
|
Primary Outcome by Genotype (HETEROZYGOTE ApoE4 CARRIERS)
Temporal
|
-0.010 SUVr
Interval -0.041 to 0.02
|
-0.030 SUVr
With 1 placebo patient, variability within the group cannot measured effectively
|
PRIMARY outcome
Timeframe: Baseline to Week 4Population: Change in composite and regional Beta Amyloid burden on Homozygote ApoE4 carriers. There are no homozygote ApoE4 carriers on the placebo arm, therefore no data can be presented on this arm.
This measures the change from baseline on treatment compared to placebo at week 4 on composite and regional beta amyloid burden according to ApoE genotype (HOMOZYGOTE ApoE4 CARRIERS) There are no homozygote ApoE4 carriers on the placebo arm, therefore no data can be presented on this arm.
Outcome measures
| Measure |
Bexarotene
n=6 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
Composite
|
0.005 SUVr
Interval -0.066 to 0.075
|
—
|
|
Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
Frontal Medial Orbital
|
-0.004 SUVr
Interval -0.077 to 0.069
|
—
|
|
Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
Anterior Cingulate
|
0.005 SUVr
Interval -0.067 to 0.077
|
—
|
|
Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
Parietal
|
0.003 SUVr
Interval -0.054 to 0.06
|
—
|
|
Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
Posterior Cingulate
|
0.037 SUVr
Interval -0.059 to 0.133
|
—
|
|
Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
Precuneus
|
0.006 SUVr
Interval -0.065 to 0.077
|
—
|
|
Primary Outcome by Genotype (HOMOZYGOTE ApoE4 CARRIERS)
Temporal
|
-0.020 SUVr
Interval -0.096 to 0.055
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 4The MMSE evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. A lower score indicates more cognitive impairment. The lowest score that any particular person can get is 0 and the highest score is 30.
Outcome measures
| Measure |
Bexarotene
n=16 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Change in MMSE Score in ALL Subjects From Baseline to Week 4
|
0.750 points
Interval -0.783 to 2.283
|
1.750 points
Interval -1.316 to 4.816
|
SECONDARY outcome
Timeframe: Baseline to Week 4The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 85 (worse). A positive change indicates cognitive worsening.
Outcome measures
| Measure |
Bexarotene
n=16 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Change in ADAS-Cog Score in ALL Subjects From Baseline to Week 4
|
0.375 points
Interval -2.153 to 2.903
|
-0.250 points
Interval -5.307 to 4.807
|
SECONDARY outcome
Timeframe: Baseline to Week 4The CDR is a clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe (CDR score of 0, 0.5, 1, 2, or 3, respectively). Higher score means more severe dementia rating. The score is based on interviews with the participant and study partner, using a structured interview that assesses six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.
Outcome measures
| Measure |
Bexarotene
n=16 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Change in the Global Clinical Dementia Rating Score in ALL Subjects From Baseline to Week 4
|
0.000 units on a scale
Interval 0.0 to 0.0
|
0.000 units on a scale
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline to Week 4The NPI is a well validated, reliable, multi-item instrument to assess psychopathology in AD based on interview with the study partner. The NPI evaluates both the frequency and severity of 10 neuropsychiatric disturbances. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1=mild, 2=moderate, 3=severe). The overall score and the score for each subscale are the product of severity and frequency. Overall score range from 0 meaning no disturbance to 144 meaning severe disturbance
Outcome measures
| Measure |
Bexarotene
n=16 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Change in NPI Scores in ALL Subjects From Baseline to Week 4
|
-2.625 points
Interval -6.783 to 1.533
|
-2.250 points
Interval -10.57 to 6.067
|
SECONDARY outcome
Timeframe: Baseline to Week 4The ADCS-ADL is an activities-of-daily-living inventory developed by the ADCS to assess functional performance in participants with AD (Galasko et al., 1997). Using a structured interview format, study partners are queried as to whether participants attempted each item in the inventory during the prior 4 weeks and their level of performance. Overall score range from 0 meaning fully independent to 78 meaning fully dependent on assistance for activities of daily living
Outcome measures
| Measure |
Bexarotene
n=16 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Change in the Activities of Daily Living (ADCS-ADL) Score in ALL Subjects From Baseline to Week 4
|
-1.938 points
Interval -4.861 to 0.986
|
-6.500 points
Interval -12.35 to -0.653
|
SECONDARY outcome
Timeframe: Baseline to Week 4Population: Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels comprised in secondary biomarker outcomes in ALL SUBJECTS. There were only a total of 17 subjects who were able to provide adequate blood sample for this serum biomarker analysis. Attempts for blood sample procurement for the other 3 subjects were unsuccessful.
Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels comprised in secondary biomarker outcomes
Outcome measures
| Measure |
Bexarotene
n=13 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS)
Beta Amyloid 40
|
7.186 pmol/L
Interval -3.673 to 18.045
|
-5.330 pmol/L
Interval -24.91 to 14.246
|
|
Secondary Outcome Measuring Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (ALL SUBJECTS)
Beta Amyloid 42
|
0.585 pmol/L
Interval -0.044 to 1.213
|
-0.900 pmol/L
Interval -2.033 to 0.233
|
SECONDARY outcome
Timeframe: Baseline to Week 4Population: Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels in non ApoE4 carriers. Of the 7 total subjects who were non-ApoE carriers, only 6 subjects were able to provide adequate blood sample for this serum biomarker analysis. Attempts for blood sample procurement for the other 1 subject were unsuccessful.
Change from baseline to week 4 in beta amyloid1-40 and beta amyloid1-42 serum levels comprised in secondary biomarker outcomes (non ApoE4 carriers)
Outcome measures
| Measure |
Bexarotene
n=3 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=3 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers)
Beta Amyloid 40
|
-3.503 pmol/L
Interval -22.84 to 15.836
|
-8.550 pmol/L
Interval -27.89 to 10.789
|
|
Serum Biomarker Outcome Level Changes From Baseline to Week 4 in Beta amyloid1-40 and Beta amyloid1-42 (Non ApoE4 Carriers)
Beta Amyloid 42
|
0.293 pmol/L
Interval -0.873 to 1.46
|
-1.127 pmol/L
Interval -2.293 to 0.04
|
SECONDARY outcome
Timeframe: Baseline to Week 4Population: There were only a total of 17 subjects who were able to provide adequate blood sample for this serum biomarker analysis. Attempts for blood sample procurement for the other 3 subjects were unsuccessful.
This measures the change in the ratio of Beta Amyloid 42 to Beta Amyloid 40 from baseline to week 4 in all subjects
Outcome measures
| Measure |
Bexarotene
n=13 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects
|
0.001 ratio
Interval -0.007 to 0.008
|
-0.005 ratio
Interval -0.019 to 0.009
|
SECONDARY outcome
Timeframe: Baseline to Week 4Population: Of the 7 total subjects who were non-ApoE carriers, only 6 subjects were able to provide adequate blood sample for this serum biomarker analysis. Attempts for blood sample procurement for the other 1 subject were unsuccessful.
This measures the change in the ratio of Beta Amyloid 42 to Beta Amyloid 40 from baseline to week 4 in non ApoE4 Carriers
Outcome measures
| Measure |
Bexarotene
n=3 Participants
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=3 Participants
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in Non ApoE4 Carriers
|
0.005 ratio
Interval -0.016 to 0.026
|
-0.005 ratio
Interval -0.026 to 0.017
|
Adverse Events
Bexarotene Treatment Arm
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Bexarotene Treatment Arm
n=16 participants at risk
75 mg of Bexarotene BID for week 1, then increasing to 150 mg BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Bexarotene: Subjects will be randomized 4:1 to receive 4 weeks of double blind treatment of either Bexarotene or Placebo
|
Placebo
n=4 participants at risk
1 placebo capsule BID for week 1, then increasing to 2 placebo capsules BID for weeks 2 to 4.
Weeks 5 to 8 is Open-label phase (150 mg BID for 4 weeks)
Placebo
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dry cough
|
6.2%
1/16 • Number of events 1 • Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
|
0.00%
0/4 • Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
|
|
Skin and subcutaneous tissue disorders
Blister on toe
|
6.2%
1/16 • Number of events 1 • Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
|
0.00%
0/4 • Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
|
|
Hepatobiliary disorders
Elevated triglyceride levels
|
81.2%
13/16 • Number of events 13 • Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
|
0.00%
0/4 • Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
|
|
Gastrointestinal disorders
Elevated cholesterol level
|
37.5%
6/16 • Number of events 6 • Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
|
0.00%
0/4 • Adverse events data were collected from the time the participants signed the informed consent forms to the Post-Treatment Follow Up Visit approximating to 4 months of time when adverse events were captured
|
Additional Information
Jeffrey Cummings, MD, ScD
Cleveland Clinic Lou Ruvo Center for Brain Health
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place