Trial Outcomes & Findings for Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies (NCT NCT03888222)
NCT ID: NCT03888222
Last Updated: 2026-07-10
Results Overview
We will determine safety and tolerability using the occurrence of adverse events (AEs) of interest, including myelosuppression, urinary, pancreatic and hepatic disorders, QTc prolongation as per Bosutinib IB.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
12 weeks
Results posted on
2026-07-10
Participant Flow
Participant milestones
| Measure |
Placebo
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
13
|
|
Overall Study
COMPLETED
|
13
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Impact of Bosutinib on Safety, Tolerability, Biomarkers and Clinical Outcomes in Dementia With Lewy Bodies
Baseline characteristics by cohort
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=9 Participants
|
1 Participants
n=27 Participants
|
2 Participants
n=267 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=9 Participants
|
12 Participants
n=27 Participants
|
24 Participants
n=267 Participants
|
|
Age, Continuous
|
74.45 years
STANDARD_DEVIATION 8.22 • n=9 Participants
|
71.43 years
STANDARD_DEVIATION 7.94 • n=27 Participants
|
73 years
STANDARD_DEVIATION 8.06 • n=267 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=9 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=267 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=9 Participants
|
12 Participants
n=27 Participants
|
25 Participants
n=267 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=9 Participants
|
1 Participants
n=27 Participants
|
1 Participants
n=267 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=9 Participants
|
12 Participants
n=27 Participants
|
24 Participants
n=267 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=267 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=9 Participants
|
13 participants
n=27 Participants
|
26 participants
n=267 Participants
|
PRIMARY outcome
Timeframe: 12 weeksWe will determine safety and tolerability using the occurrence of adverse events (AEs) of interest, including myelosuppression, urinary, pancreatic and hepatic disorders, QTc prolongation as per Bosutinib IB.
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Falls
|
3 events
|
3 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Pain
|
1 events
|
3 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Flu
|
1 events
|
0 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Liver Transaminases
|
0 events
|
1 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Post-lumbar puncture headache
|
0 events
|
1 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Dizziness
|
1 events
|
1 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Urinary incontinence
|
0 events
|
1 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Urinary tract infection
|
0 events
|
1 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Upper respiratory infection
|
1 events
|
0 events
|
|
Safety and Tolerability Go/NoGo (25% Discontinuations) Will be Determined Based on Any Emergent Adverse Events.
Lesion
|
1 events
|
0 events
|
SECONDARY outcome
Timeframe: Change between baseline (BSL) and Week-12Phospho-ABL(PanTyr) and phospho-SRC(Y416) are critical drivers in the pathogenesis of various neurodegenerative diseases. We will examine the changes in CSF and Plasma phospho-ABL(PanTyr) and phospho-SRC(Y416) absorbance (ABS) levels at baseline and 3 months. The magnitude of the absorbance is proportional to the quantity of tyrosine-phosphorylated protein.
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
Baseline CSF phospho-ABL(PanTyr)
|
0.09 AU
Standard Deviation 0.01
|
0.10 AU
Standard Deviation 0.01
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
12 weeks CSF phospho-ABL(PanTyr)
|
0.11 AU
Standard Deviation 0.01
|
0.11 AU
Standard Deviation 0.01
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
Change from Baseline CSFphospho-ABL(PanTyr)
|
0.02 AU
Standard Deviation 0.01
|
0.01 AU
Standard Deviation 0.01
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
Baseline CSF phospho-SRC(Y416)
|
0.06 AU
Standard Deviation 0
|
0.06 AU
Standard Deviation 0
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
12 weeks CSF phospho-SRC(Y416)
|
0.08 AU
Standard Deviation 0.04
|
0.08 AU
Standard Deviation 0.03
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
Change from Baseline CSF phospho-SRC(Y416)
|
0.02 AU
Standard Deviation 0.04
|
0.02 AU
Standard Deviation 0.02
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
Baseline Plasma phospho-ABL(PanTyr)
|
0.08 AU
Standard Deviation 0.00
|
0.075 AU
Standard Deviation 0.010
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
12 weeks Plasma phospho-ABL(PanTyr)
|
0.09 AU
Standard Deviation 0.02
|
0.102 AU
Standard Deviation 0.034
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
Change from Baseline Plasma phospho-ABL(PanTyr)
|
0.01 AU
Standard Deviation 0.02
|
0.026 AU
Standard Deviation 0.033
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
Baseline Plasma phospho-SRC(Y416)
|
0.066 AU
Standard Deviation 0.01
|
0.065 AU
Standard Deviation 0.011
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
12 weeks Plasma phospho-SRC(Y416)
|
0.074 AU
Standard Deviation 0.02
|
0.088 AU
Standard Deviation 0.020
|
|
Determine Changes in Absorbance Levels (ABS) in DLB Related CSF and Plasma Tyrosine Kinases
Change from Baseline Plasma phospho-SRC(Y416)
|
0.008 AU
Standard Deviation 0.02
|
0.024 AU
Standard Deviation 0.019
|
SECONDARY outcome
Timeframe: 12 weeksTo determine the Cmax (ng/ml), we will measure Bosutinib in both the CSF and Plasma using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Determine the Maximum Concentration (Cmax) (ng/ml) of Bosutinib in the CSF and Plasma.
Plasma Cmax
|
0 ng/ml
Standard Deviation 0
|
29.93 ng/ml
Standard Deviation 10.27
|
|
Determine the Maximum Concentration (Cmax) (ng/ml) of Bosutinib in the CSF and Plasma.
CSF Cmax
|
0 ng/ml
Standard Deviation 0
|
0.5 ng/ml
Standard Deviation 0.17
|
SECONDARY outcome
Timeframe: 12 weeksTo determine the Cmax (nM), we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Determine the Maximum Concentration (Cmax) (nM) of Bosutinib in the CSF and Plasma.
Plasma Cmax
|
0 nM
Standard Deviation 0
|
56.43 nM
Standard Deviation 19.34
|
|
Determine the Maximum Concentration (Cmax) (nM) of Bosutinib in the CSF and Plasma.
CSF Cmax
|
0 nM
Standard Deviation 0
|
0.94 nM
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: 12 weeksTo determine the Tmax, we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Determine the Maximum Time (Tmax) Bosutinib Peaks in CSF and Plasma.
Plasma Tmax
|
0 hours
Standard Deviation 0
|
4 hours
Standard Deviation 0
|
|
Determine the Maximum Time (Tmax) Bosutinib Peaks in CSF and Plasma.
CSF Tmax
|
0 hours
Standard Deviation 0
|
3 hours
Standard Deviation 0
|
SECONDARY outcome
Timeframe: 12 weeksTo determine the AUC (ng/ml\*hours) , we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Determine the Area Under the Curve (AUC) (ng/ml*Hours) for Bosutinib in CSF and Plasma.
Plasma AUC (0-4hrs)
|
0 ng/ml*hours
Standard Deviation 0
|
73.1 ng/ml*hours
Standard Deviation 6.63
|
|
Determine the Area Under the Curve (AUC) (ng/ml*Hours) for Bosutinib in CSF and Plasma.
CSF AUC (0-4hrs)
|
0 ng/ml*hours
Standard Deviation 0
|
1.15 ng/ml*hours
Standard Deviation 0.15
|
SECONDARY outcome
Timeframe: 12 weeksTo determine the AUC (nM\*hours) , we will measure Bosutinib in both the CSF and Plasma and perform population pharmacokinetics using Liquid chromatography-tandem mass spectrometry (LC-MS/MS)
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Determine the Area Under the Curve (AUC) (nM*Hours) for Bosutinib in CSF and Plasma.
Plasma AUC (0-4hrs)
|
0 nM*hr
Standard Deviation 0
|
137.8 nM*hr
Standard Deviation 12.5
|
|
Determine the Area Under the Curve (AUC) (nM*Hours) for Bosutinib in CSF and Plasma.
CSF AUC (0-4hrs)
|
0 nM*hr
Standard Deviation 0
|
2.16 nM*hr
Standard Deviation 0.21
|
SECONDARY outcome
Timeframe: Change between baseline (BSL) and Week-12We will examine the changes in CSF and Plasma Abeta40, Abeta42, total tau, ptau181 and total and oligomeric alpha-synuclein at baseline, week-12, and the change between baseline and week-12.
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF AB40
|
5157 pg/ml
Standard Deviation 1197.3
|
5089.9 pg/ml
Standard Deviation 1460
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF AB42
|
508.4 pg/ml
Standard Deviation 188.6
|
487 pg/ml
Standard Deviation 166.2
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF tTau
|
502.1 pg/ml
Standard Deviation 173.6
|
560.1 pg/ml
Standard Deviation 300.8
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF pTau(181)
|
78.1 pg/ml
Standard Deviation 36.7
|
67.2 pg/ml
Standard Deviation 38.5
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF total a-syn
|
1347.7 pg/ml
Standard Deviation 527.5
|
1805.2 pg/ml
Standard Deviation 902
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF aggregated a-syn
|
46.6 pg/ml
Standard Deviation 23.7
|
48.4 pg/ml
Standard Deviation 17.3
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline plasma total a-syn
|
8593.1 pg/ml
Standard Deviation 4606.3
|
13861.9 pg/ml
Standard Deviation 14946.9
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline plasma aggregated a-syn
|
31.3 pg/ml
Standard Deviation 16.1
|
32.4 pg/ml
Standard Deviation 10.9
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF AB40
|
5419.9 pg/ml
Standard Deviation 1319.3
|
539.2 pg/ml
Standard Deviation 1524
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF AB42
|
513.8 pg/ml
Standard Deviation 233.1
|
525 pg/ml
Standard Deviation 161.8
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF tTau
|
494.5 pg/ml
Standard Deviation 237.4
|
476.4 pg/ml
Standard Deviation 191
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF pTau(181)
|
67.2 pg/ml
Standard Deviation 36.7
|
66.2 pg/ml
Standard Deviation 39.7
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF total a-syn
|
1758.3 pg/ml
Standard Deviation 1251.9
|
1488.9 pg/ml
Standard Deviation 1050.9
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF aggregated a-syn
|
71.6 pg/ml
Standard Deviation 21.3
|
67.8 pg/ml
Standard Deviation 13.9
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-122 plasma total a-syn
|
10184.3 pg/ml
Standard Deviation 5849.5
|
17206.2 pg/ml
Standard Deviation 12878
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 plasma aggregated a-syn
|
51.8 pg/ml
Standard Deviation 33.2
|
45.9 pg/ml
Standard Deviation 24.6
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF AB40
|
263 pg/ml
Standard Deviation 702.3
|
309.3 pg/ml
Standard Deviation 795
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF AB42
|
5.4 pg/ml
Standard Deviation 106.7
|
37.9 pg/ml
Standard Deviation 66.8
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF tTau
|
-7.5 pg/ml
Standard Deviation 287.9
|
-10.3 pg/ml
Standard Deviation 96.1
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF pTau(181)
|
-10.9 pg/ml
Standard Deviation 30
|
-0.986 pg/ml
Standard Deviation 12
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF Total a-syn
|
55.1 pg/ml
Standard Deviation 542
|
-479.4 pg/ml
Standard Deviation 691.8
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF aggregated a-syn
|
25 pg/ml
Standard Deviation 17.4
|
19.4 pg/ml
Standard Deviation 20.3
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline Plasma total a-syn
|
1591.2 pg/ml
Standard Deviation 5707.7
|
3344.3 pg/ml
Standard Deviation 19774.5
|
|
Changes in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline Plasma aggregated a-syn
|
20.5 pg/ml
Standard Deviation 38.3
|
12.1 pg/ml
Standard Deviation 26.5
|
SECONDARY outcome
Timeframe: 12 weeksWe will examine the ratio changes in CSF and Plasma AB42 to AB40, ptau(181 )to AB42, pTau(181) to tTau, aggregated a-syn to total a-syn at baseline, 12 weeks, and between baseline and week-12.
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF AB42/ AB40
|
0.01 ratio
Standard Deviation 0.027
|
0.10 ratio
Standard Deviation 0.02
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF pTau(181)/ AB42
|
0.18 ratio
Standard Deviation 0.11
|
0.15 ratio
Standard Deviation 0.11
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF pTau(181)/ tTau
|
0.16 ratio
Standard Deviation 0.07
|
0.13 ratio
Standard Deviation 0.05
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF aggregated/ total a-syn
|
0.04 ratio
Standard Deviation 0.02
|
0.03 ratio
Standard Deviation 0.03
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF/plasma total a-synuclein
|
0.21 ratio
Standard Deviation 0.16
|
0.26 ratio
Standard Deviation 0.22
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF/plasma aggregated a-synuclein
|
1.66 ratio
Standard Deviation 0.86
|
1.47 ratio
Standard Deviation 0.54
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline Plasma aggregated/total a-synuclein
|
0.005 ratio
Standard Deviation 0.003
|
0.004 ratio
Standard Deviation 0.003
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline CSF aggregated/Plasma total a-syn
|
0.04 ratio
Standard Deviation 0.02
|
0.03 ratio
Standard Deviation 0.03
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline Plasma aggregated/CSF total a-syn
|
0.03 ratio
Standard Deviation 0.02
|
0.02 ratio
Standard Deviation 0.02
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF AB42/ AB40
|
0.10 ratio
Standard Deviation 0.03
|
0.10 ratio
Standard Deviation 0.02
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF pTau(181)/ AB42
|
0.15 ratio
Standard Deviation 0.08
|
0.14 ratio
Standard Deviation 0.10
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF pTau(181)/ tTau
|
0.15 ratio
Standard Deviation 0.101
|
0.14 ratio
Standard Deviation 0.07
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF aggregated/total a-syn
|
0.05 ratio
Standard Deviation 0.03
|
0.06 ratio
Standard Deviation 0.03
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF/plasma total a-synuclein
|
0.24 ratio
Standard Deviation 0.23
|
0.13 ratio
Standard Deviation 0.12
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF/plasma aggregated a-synuclein
|
1.53 ratio
Standard Deviation 0.68
|
2.71 ratio
Standard Deviation 2.58
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 Plasma aggregated/total a-synuclein
|
0.008 ratio
Standard Deviation 0.008
|
0.004 ratio
Standard Deviation 0.003
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 CSF aggregated/Plasma total a-syn
|
0.01 ratio
Standard Deviation 0.009
|
0.006 ratio
Standard Deviation 0.004
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 Plasma aggregated/CSF total a-syn
|
0.04 ratio
Standard Deviation 0.03
|
0.04 ratio
Standard Deviation 0.03
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF AB42/ AB40
|
0.01 ratio
Standard Deviation 0.02
|
0.002 ratio
Standard Deviation 0.006
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF pTau(181)/ AB42
|
-0.03 ratio
Standard Deviation 0.05
|
-0.01 ratio
Standard Deviation 0.03
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF pTau(181)/ tTau
|
-0.01 ratio
Standard Deviation 0.09
|
0.02 ratio
Standard Deviation 0.08
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF aggregated/ total a-syn
|
0.01 ratio
Standard Deviation 0.03
|
0.03 ratio
Standard Deviation 0.02
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF/plasma total a-synuclein
|
0.03 ratio
Standard Deviation 0.14
|
-0.13 ratio
Standard Deviation 0.24
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF/plasma aggregated a-synuclein
|
-0.25 ratio
Standard Deviation 1.41
|
1.03 ratio
Standard Deviation 2.51
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline Plasma aggregated/total a-synuclein
|
0.003 ratio
Standard Deviation 0.008
|
-0.00009 ratio
Standard Deviation 0.004
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline CSF aggregated/Plasma total a-syn
|
-0.25 ratio
Standard Deviation 1.41
|
-0.0006 ratio
Standard Deviation 0.006
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline Plasma aggregated/CSF total a-syn
|
0.008 ratio
Standard Deviation 0.04
|
0.01 ratio
Standard Deviation 0.03
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline DOPAC CSF/plasma
|
0.25 ratio
Standard Deviation 0.09
|
0.33 ratio
Standard Deviation 0.12
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 DOPAC CSF/plasma
|
0.25 ratio
Standard Deviation 0.18
|
0.37 ratio
Standard Deviation 0.12
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline DOPAC CSF/plasma
|
0.00017 ratio
Standard Deviation 0.14
|
0.04 ratio
Standard Deviation 0.11
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Baseline HVA CSF/plasma
|
1.03 ratio
Standard Deviation 0.48
|
1.35 ratio
Standard Deviation 0.95
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Week-12 HVA CSF/plasma
|
1.0 ratio
Standard Deviation 0.81
|
1.38 ratio
Standard Deviation 0.57
|
|
Change in Ratios in Dementia Lewy Body (DLB) Related CSF and Plasma Biomarkers
Change from Baseline HVA CSF/plasma
|
-0.03 ratio
Standard Deviation 0.73
|
0.03 ratio
Standard Deviation 0.82
|
SECONDARY outcome
Timeframe: 12 weeksWe will measure the levels of DOPAC AND Homovanillic Acid (HVA) using liquid-liquid extraction and Liquid chromatography-tandem mass spectrometry (LC-MS/MS) in CSF and plasma samples at baseline (BSL), 12 weeks, and between baseline and 12 weeks (WK12).
Outcome measures
| Measure |
Placebo
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 Participants
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Measure HVA and DOPAC in CSF and Plasma
Baseline CSF DOPAC
|
0.65 ng/ml
Standard Deviation 0.31
|
0.56 ng/ml
Standard Deviation 0.23
|
|
Measure HVA and DOPAC in CSF and Plasma
Baseline CSF HVA
|
50.7 ng/ml
Standard Deviation 27.66
|
40.34 ng/ml
Standard Deviation 27.58
|
|
Measure HVA and DOPAC in CSF and Plasma
Baseline Plasma DOPAC
|
3.48 ng/ml
Standard Deviation 3.19
|
2.09 ng/ml
Standard Deviation 1.76
|
|
Measure HVA and DOPAC in CSF and Plasma
Baseline Plasma HVA
|
62.93 ng/ml
Standard Deviation 50.08
|
34.57 ng/ml
Standard Deviation 27.69
|
|
Measure HVA and DOPAC in CSF and Plasma
Week-12 CSF DOPAC
|
0.62 ng/ml
Standard Deviation 0.24
|
0.62 ng/ml
Standard Deviation 0.46
|
|
Measure HVA and DOPAC in CSF and Plasma
Week-12 CSF HVA
|
50.27 ng/ml
Standard Deviation 24.69
|
47.9 ng/ml
Standard Deviation 54.04
|
|
Measure HVA and DOPAC in CSF and Plasma
Week-12 Plasma DOPAC
|
5.10 ng/ml
Standard Deviation 5.19
|
3.66 ng/ml
Standard Deviation 6.74
|
|
Measure HVA and DOPAC in CSF and Plasma
Week-12 Plasma HVA
|
81.7 ng/ml
Standard Deviation 60.39
|
41.77 ng/ml
Standard Deviation 48.16
|
|
Measure HVA and DOPAC in CSF and Plasma
Change from Baseline CSF DOPAC
|
-0.03 ng/ml
Standard Deviation 0.19
|
0.06 ng/ml
Standard Deviation 0.30
|
|
Measure HVA and DOPAC in CSF and Plasma
Change from Baseline CSF HVA
|
-0.43 ng/ml
Standard Deviation 15.21
|
7.56 ng/ml
Standard Deviation 32.18
|
|
Measure HVA and DOPAC in CSF and Plasma
Change from Baseline Plasma DOPAC
|
1.62 ng/ml
Standard Deviation 3.19
|
1.74 ng/ml
Standard Deviation 7.05
|
|
Measure HVA and DOPAC in CSF and Plasma
Change from Baseline Plasma HVA
|
18.77 ng/ml
Standard Deviation 34.59
|
9.86 ng/ml
Standard Deviation 44.75
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
100 mg of Bosutinib
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=13 participants at risk
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) capsule orally once daily for 3 months (90 days).
Placebo Oral Tablet: Fifteen (15) patients in group 1 will receive the matching placebo("sugar pill") one (1) tablet orally once daily for 3 months (90 days) .
|
100 mg of Bosutinib
n=13 participants at risk
Thirty (30) participants will be recruited and randomized into 2 groups (arms) (1:1) .Fifteen (15) patients in group 2 will receive the 100 mg of Bosutinib one (1) capsule orally once daily for 3 months (90 days).
Bosutinib Oral Tablet: Fifteen (15) patients in group 1 will receive the 100 mg of Bosutinib one (1) tablet orally once daily for 3 months (90 days) .
|
|---|---|---|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/13 • Adverse event data was collected over the course of 16 weeks for each patient.
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
Renal and urinary disorders
Urinary tract infection
|
0.00%
0/13 • Adverse event data was collected over the course of 16 weeks for each patient.
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
0.00%
0/13 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
Skin and subcutaneous tissue disorders
Lesions
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
0.00%
0/13 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
General disorders
Falls
|
23.1%
3/13 • Number of events 3 • Adverse event data was collected over the course of 16 weeks for each patient.
|
15.4%
2/13 • Number of events 3 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
General disorders
Pain
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
15.4%
2/13 • Number of events 3 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
General disorders
Flu
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
0.00%
0/13 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
Hepatobiliary disorders
Liver transaminases
|
0.00%
0/13 • Adverse event data was collected over the course of 16 weeks for each patient.
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
Nervous system disorders
Post-lumbar puncture headache
|
0.00%
0/13 • Adverse event data was collected over the course of 16 weeks for each patient.
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
|
Nervous system disorders
Dizziness
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
7.7%
1/13 • Number of events 1 • Adverse event data was collected over the course of 16 weeks for each patient.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place