Trial Outcomes & Findings for Study to Evaluate the Preliminary Safety, Efficacy, PK and PD of Bryostatin 1 in Patients With Alzheimer's Disease (NCT NCT02221947)
NCT ID: NCT02221947
Last Updated: 2017-11-06
Results Overview
Evaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
9 participants
Primary outcome timeframe
Within 2 weeks of study drug dosing
Results posted on
2017-11-06
Participant Flow
Participant milestones
| Measure |
Bryostatin 1
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
|
Placebo
single dose of placebo, intravenous infusion over 1 hour
Placebo: Placebo, single dose via intravenous infusion over 1 hour.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
3
|
|
Overall Study
COMPLETED
|
6
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate the Preliminary Safety, Efficacy, PK and PD of Bryostatin 1 in Patients With Alzheimer's Disease
Baseline characteristics by cohort
| Measure |
Bryostatin 1
n=6 Participants
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
|
Placebo
n=3 Participants
single dose of placebo, intravenous infusion over 1 hour
Placebo: Placebo, single dose via intravenous infusion over 1 hour.
|
Total
n=9 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Age, Continuous
|
72.5 years
STANDARD_DEVIATION 8.04 • n=5 Participants
|
70.7 years
STANDARD_DEVIATION 7.23 • n=7 Participants
|
71.9 years
STANDARD_DEVIATION 7.37 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
3 participants
n=7 Participants
|
9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Within 2 weeks of study drug dosingEvaluate the safety and tolerability of bryostatin 1 (hereinafter referred to as bryostatin) in patients with Alzheimer's Disease (AD) following a single intravenous (IV) dose.
Outcome measures
| Measure |
Bryostatin 1
n=6 Participants
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
|
Placebo
n=3 Participants
single dose of placebo, intravenous infusion over 1 hour
Placebo: Placebo, single dose via intravenous infusion over 1 hour.
|
|---|---|---|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Dizziness
|
0 event
|
1 event
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Headache
|
1 event
|
1 event
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Rash Papular
|
0 event
|
1 event
|
PRIMARY outcome
Timeframe: 48 hours post start of study drug infusionHopkins Verbal Learning Test - Revised (HVLT-R) delayed recall; change from baseline. HVLT consists of a 12-item word list drawn from 3 semantic categories, presented in 3 learning trials. Score range = 0-12. The lower the number, the more impaired. Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Total Score Range: 0-20. Each portion of the drawing is scored 1 point for correctness and completeness and 1 point for being placed properly in relation to the rest of the drawing. Drawing and placement scores are summed for the item total. To obtain subtest total score, the drawing and placement scores are summed for each item. The lower the number, the more impaired.
Outcome measures
| Measure |
Bryostatin 1
n=6 Participants
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
|
Placebo
n=3 Participants
single dose of placebo, intravenous infusion over 1 hour
Placebo: Placebo, single dose via intravenous infusion over 1 hour.
|
|---|---|---|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
HVLT-R at 48hrs (change from baseline)
|
1.3 units on a scale, change from baseline
Standard Deviation 2.16
|
3.7 units on a scale, change from baseline
Standard Deviation 1.15
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
RBANS figure recall at 48hrs (CBL)
|
4.5 units on a scale, change from baseline
Standard Deviation 4.14
|
6.7 units on a scale, change from baseline
Standard Deviation 3.06
|
SECONDARY outcome
Timeframe: Specified timepoints within 2 weeks post study drug infusionHVLT-R (Hopkins Verbal Learning Test-Revised™) delayed recall (change from baseline). A 12-item word list: 3 learning trials. Score range = 0-12. The lower the number, the more impaired. Repeatable Battery of Assessments for Neuropsychological Status (RBANS) figure recall; change from baseline. Score Range: 0-20. The lower the number, the more impaired. Digit Symbol Coding (observed), Score range: 0-125. The lower the number, the more impaired. Clinical Dementia Rating- Sum of Boxes (CDR-SB, observed). Sum of 6 investigated domains (Memory, Orientation, Judgment and Problem Solving, Community Affairs, Home and Hobbies, Personal Care). Each subtest range is 0-3; Sum of all 6 subtest scores gives total CDR-SB score (range= 0-18).The higher the number, the more impaired. Mini Mental State Exam, version 2 (MMSE-2), change from baseline. The MMSE-2 measures aspects of cognitionon a scale of 0-30. Lower scores indicate greater cognitive impairment.
Outcome measures
| Measure |
Bryostatin 1
n=6 Participants
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
|
Placebo
n=3 Participants
single dose of placebo, intravenous infusion over 1 hour
Placebo: Placebo, single dose via intravenous infusion over 1 hour.
|
|---|---|---|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
RBANS 2 Wks Figure Recall (CBL)
|
4.2 units on a scale
Standard Deviation 5.60
|
7.3 units on a scale
Standard Deviation 3.06
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
Digit Symbol Coding 2 wks post start of infusion
|
38.3 units on a scale
Standard Deviation 7.61
|
52.7 units on a scale
Standard Deviation 6.66
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
MMSE-2 3hrs post start of inf (change)
|
1.8 units on a scale
Standard Deviation 1.72
|
-1.0 units on a scale
Standard Deviation 2.65
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
HVLT-R 24hr Delayed Recall (change from baseline)
|
0.5 units on a scale
Standard Deviation 3.27
|
1.3 units on a scale
Standard Deviation 2.52
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
HVLT-R 2 Wks Delayed Recall (change from baseline)
|
0.3 units on a scale
Standard Deviation 1.63
|
2.3 units on a scale
Standard Deviation 2.52
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
RBANS 24hr Figure Recall (change from baseline)
|
4.7 units on a scale
Standard Deviation 4.76
|
6.0 units on a scale
Standard Deviation 2.65
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
HVLT-R delayed recall of stimuli at 48hr (CBL)
|
-1.2 units on a scale
Standard Deviation 1.17
|
2.7 units on a scale
Standard Deviation 2.08
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
Digit Symbol Coding baseline (observed)
|
32.2 units on a scale
Standard Deviation 9.13
|
42.3 units on a scale
Standard Deviation 12.50
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
Digit Symbol Coding 24hrs post start of infusion
|
36.0 units on a scale
Standard Deviation 10.75
|
49.0 units on a scale
Standard Deviation 4.58
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
Digit Symbol Coding 48hrs post start of infusion
|
37.3 units on a scale
Standard Deviation 11.64
|
53.7 units on a scale
Standard Deviation 4.73
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
CDR, CDR-SB baseline (observed)
|
1.3 units on a scale
Standard Deviation 0.98
|
0.7 units on a scale
Standard Deviation 0.29
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
CDR, CDR-SB 2wks (observed)
|
1.5 units on a scale
Standard Deviation 1.00
|
0.7 units on a scale
Standard Deviation 0.29
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
Digit Symbol Coding 3hrs post start of inf (observ
|
32.7 units on a scale
Standard Deviation 6.86
|
45.3 units on a scale
Standard Deviation 11.50
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
MMSE-2 at 72hrs (change from Baseline)
|
2.6 units on a scale
Standard Deviation 1.52
|
3.3 units on a scale
Standard Deviation 2.52
|
|
Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
MMSE-2 at 2wks (change from Baseline)
|
3.3 units on a scale
Standard Deviation 1.86
|
4.7 units on a scale
Standard Deviation 1.15
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Bryostatin plasma concentration pre-dose and at 15 min, 30 min, 1 hr, 1.5 hr, 2hr, 3hr and 6rs post dose.Population: Subjects who received a single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour (PK population)
Preliminary evaluation of pharmacokinetics and pharmacodynamics (Cmax, Tmax, AUClast).
Outcome measures
| Measure |
Bryostatin 1
n=6 Participants
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
|
Placebo
single dose of placebo, intravenous infusion over 1 hour
Placebo: Placebo, single dose via intravenous infusion over 1 hour.
|
|---|---|---|
|
Pharmacokinetic Parameters of Bryostatin.
predose Bryostatin Plasma Concentration (ng/mL)
|
0.0 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.0
|
—
|
|
Pharmacokinetic Parameters of Bryostatin.
Concentration 15 min post (ng/mL)
|
0.880 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.133
|
—
|
|
Pharmacokinetic Parameters of Bryostatin.
Concentration 30 min post (ng/mL)
|
0.941 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.168
|
—
|
|
Pharmacokinetic Parameters of Bryostatin.
Concentration 1 hr post (ng/mL)
|
1.04 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.309
|
—
|
|
Pharmacokinetic Parameters of Bryostatin.
Concentration 1.5 hrs post (ng/mL)
|
0.181 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.148
|
—
|
|
Pharmacokinetic Parameters of Bryostatin.
Concentration 2 hrs post (ng/mL)
|
0.0702 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.109
|
—
|
|
Pharmacokinetic Parameters of Bryostatin.
Concentration 3 hrs post (ng/mL)
|
0.0 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.0
|
—
|
|
Pharmacokinetic Parameters of Bryostatin.
Concentration 6 hrs post (ng/mL)
|
0.0 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.0
|
—
|
|
Pharmacokinetic Parameters of Bryostatin.
Cmax (ng/mL)
|
1.09 bryostatin plasma concentration (ng/mL)
Standard Deviation 0.246
|
—
|
Adverse Events
Bryostatin 1
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Bryostatin 1
n=6 participants at risk
single dose of 25 μg/m2 bryostatin, intravenous infusion over 1 hour
Bryostatin 1: 25 μg/m2 bryostatin 1, single dose via intravenous infusion over 1 hour.
|
Placebo
n=3 participants at risk
single dose of placebo, intravenous infusion over 1 hour
Placebo: Placebo, single dose via intravenous infusion over 1 hour.
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
0.00%
0/6 • Adverse event collection began 28 days prior to dosing and continued until 4 weeks after dosing. Ongoing AEs were followed until resolved or stabilized.
|
33.3%
1/3 • Number of events 1 • Adverse event collection began 28 days prior to dosing and continued until 4 weeks after dosing. Ongoing AEs were followed until resolved or stabilized.
|
|
General disorders
Headache
|
16.7%
1/6 • Number of events 1 • Adverse event collection began 28 days prior to dosing and continued until 4 weeks after dosing. Ongoing AEs were followed until resolved or stabilized.
|
33.3%
1/3 • Number of events 1 • Adverse event collection began 28 days prior to dosing and continued until 4 weeks after dosing. Ongoing AEs were followed until resolved or stabilized.
|
|
Skin and subcutaneous tissue disorders
Rash Papular
|
0.00%
0/6 • Adverse event collection began 28 days prior to dosing and continued until 4 weeks after dosing. Ongoing AEs were followed until resolved or stabilized.
|
33.3%
1/3 • Number of events 1 • Adverse event collection began 28 days prior to dosing and continued until 4 weeks after dosing. Ongoing AEs were followed until resolved or stabilized.
|
Additional Information
Vice President, Regulatory Affairs
Neurotrope BioScience, Inc
Phone: 973-826-5109
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee PI cannot disclose trial results without permission from sponsor.
- Publication restrictions are in place
Restriction type: OTHER