Trial Outcomes & Findings for A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease (NCT NCT02431468)

NCT ID: NCT02431468

Last Updated: 2018-07-06

Results Overview

Evaluations of adverse events (AEs), serious adverse events (SAEs), Adverse event of special interest - myalgia

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

147 participants

Primary outcome timeframe

Baseline through 30 days post end of treatment (up to Day 107)

Results posted on

2018-07-06

Participant Flow

Planned: 250 subjects to be screened for a total of 140 subjects randomized 1:1:1 to one of three treatment arms: 20μg, 40μg or placebo Actual: 264 subjects were screened. 147 individual subjects were randomized and of those, 141 were dosed with trial drug.

Participant milestones

Participant milestones
Measure	Bryostatin 1 20ug Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
Overall Study STARTED	46	47	48
Overall Study COMPLETED	38	29	39
Overall Study NOT COMPLETED	8	18	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Bryostatin 1 20ug Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
Overall Study Adverse Event	2	4	5
Overall Study Withdrawal by Subject	4	12	2
Overall Study noncompliance, investigator termination,	2	2	2

Baseline Characteristics

A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bryostatin 1 20ug n=46 Participants Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug n=47 Participants Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo n=48 Participants Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.	Total n=141 Participants Total of all reporting groups
Age, Continuous	71.2 years STANDARD_DEVIATION 8.40 • n=39 Participants	70.2 years STANDARD_DEVIATION 7.53 • n=41 Participants	73.5 years STANDARD_DEVIATION 7.68 • n=35 Participants	71.7 years STANDARD_DEVIATION 7.94 • n=31 Participants
Sex: Female, Male Female	26 Participants n=39 Participants	22 Participants n=41 Participants	23 Participants n=35 Participants	71 Participants n=31 Participants
Sex: Female, Male Male	20 Participants n=39 Participants	25 Participants n=41 Participants	25 Participants n=35 Participants	70 Participants n=31 Participants
Race/Ethnicity, Customized White	42 Participants n=39 Participants	46 Participants n=41 Participants	45 Participants n=35 Participants	133 Participants n=31 Participants
Race/Ethnicity, Customized African American	3 Participants n=39 Participants	1 Participants n=41 Participants	3 Participants n=35 Participants	7 Participants n=31 Participants
Race/Ethnicity, Customized Asian	1 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants	1 Participants n=31 Participants
Region of Enrollment United States	46 participants n=39 Participants	47 participants n=41 Participants	48 participants n=35 Participants	141 participants n=31 Participants
Mini Mental State Exam-version 2 (MMSE-2) baseline scores 4-9	18 Participants n=39 Participants	20 Participants n=41 Participants	19 Participants n=35 Participants	57 Participants n=31 Participants
Mini Mental State Exam version 2 (MMSE-2) baseline score 10-15	28 Participants n=39 Participants	27 Participants n=41 Participants	29 Participants n=35 Participants	84 Participants n=31 Participants

PRIMARY outcome

Timeframe: Baseline through 30 days post end of treatment (up to Day 107)

Population: Safety Analysis Set

Evaluations of adverse events (AEs), serious adverse events (SAEs), Adverse event of special interest - myalgia

Outcome measures

Outcome measures
Measure	Bryostatin 1 20ug n=46 Participants Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug n=47 Participants Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo n=48 Participants Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 20ug Without Memantine Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	Bryostatin 1 40ug Without Memantine Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	Placebo Without Memantine Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks.
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events # of Subjects with Fatal TEAE	0 participants	1 participants	0 participants	—	—	—
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events Number of Subjects w Treatment Emergent AE (TEAE)	30 participants	39 participants	28 participants	—	—	—
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events # of Subjects w Treatment Related TEAE	17 participants	24 participants	8 participants	—	—	—
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events # of Subjects w TEAE leading to treatment discont.	1 participants	3 participants	2 participants	—	—	—
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events # of Subjects with Serious TEAE	1 participants	6 participants	3 participants	—	—	—
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events # of Subjects with Treatment Related Serious TEAE	1 participants	4 participants	0 participants	—	—	—
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events # of Subjects w Treatment Emergent Myalgia	1 participants	4 participants	0 participants	—	—	—
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events # of Subjects w Serious Treatment Emergent Myalgia	0 participants	0 participants	0 participants	—	—	—

PRIMARY outcome

Timeframe: Primary analysis at Week 13 (day 91) after 12 weeks of treatment (up to day 107)

Population: The Full Analysis Set (FAS), consistent with a modified intention-to-treat principle (mITT), was defined as all randomized subjects who received at least one dose of randomized trial medication and who had at least one post-baseline assessment.

The primary statistical objective for efficacy was to estimate the effect of bryostatin on the mean change in the total SIB score after 12 weeks of treatment, assessed at Week 13 (day 91). Efficacy analyses were conducted according to randomized groups. The SIB is used to assess cognition in subjects with moderate and severe AD. It is divided into nine subscales that include attention, language, orientation, memory, praxis, visuospatial ability, construction, social skills, orienting head to name. Non-verbal responses are allowed, thus decreasing the need for language output. Forty questions are included with a point score range of 0-100. Lower scores indicate greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Bryostatin 1 20ug n=44 Participants Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug n=45 Participants Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo n=46 Participants Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 20ug Without Memantine Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	Bryostatin 1 40ug Without Memantine Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	Placebo Without Memantine Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks.
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) Week 13 Full Analysis Set (FAS)	1.6 mean change from baseline in SIB score Standard Deviation 7.10	0.8 mean change from baseline in SIB score Standard Deviation 6.58	-0.4 mean change from baseline in SIB score Standard Deviation 9.02	—	—	—
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) Week 13 Completer Analysis Set (CAS)	1.6 mean change from baseline in SIB score Standard Deviation 7.10	0.8 mean change from baseline in SIB score Standard Deviation 6.58	-0.7 mean change from baseline in SIB score Standard Deviation 9.02	—	—	—
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) 30-Day Followup Full Analysis Set	2.3 mean change from baseline in SIB score Standard Deviation 8.17	0.6 mean change from baseline in SIB score Standard Deviation 7.51	-2.7 mean change from baseline in SIB score Standard Deviation 11.44	—	—	—
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) 30-Day Followup Completer Analysis Set	2.3 mean change from baseline in SIB score Standard Deviation 8.17	0.9 mean change from baseline in SIB score Standard Deviation 7.85	-2.7 mean change from baseline in SIB score Standard Deviation 11.44	—	—	—

SECONDARY outcome

Timeframe: Week 5, Week 9, Week 13

Population: The number of participants analyzed over the course of the study diminished as a result of attrition.

* Change from baseline in the Severe Impairment Battery (SIB) at Weeks 5 and 9. Assesses cognition. Score range 0-100. Lower scores indicate greater cognitive impairment. * Change from baseline in Alzheimer Disease Cooperative Study Activities of Daily Living Inventory-Severe Impairment Version (ADCS-ADL-SEV) at Weeks 5, 9,13. A 19-item test of the performance of activities of daily living. Total score range 0-54; lower scores indicate greater functional impairment. * Change from baseline in MMSE-2 at Weeks 5, 9 and 13. Tests selected aspects of cognition on a scale of 0-30. Lower scores indicate greater cognitive impairment. * Change from baseline in Neuropsychiatric Inventory (NPI) at Weeks 5, 9,13. Caregiver interview assesses 12 behavioral disturbances. Scores range from 0-144; higher scores indicate greater behavioral disturbances. * Clinical Global Impression of Improvement (CGI-I) at Weeks 5, 9, 13. A 7-point scale range from (1) very much improved to (7) very much worse.

Outcome measures

Outcome measures
Measure	Bryostatin 1 20ug n=46 Participants Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug n=47 Participants Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo n=48 Participants Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 20ug Without Memantine Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	Bryostatin 1 40ug Without Memantine Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	Placebo Without Memantine Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks.
Secondary Efficacy Endpoints Week 9 ADCS-ADL-SIV : FAS	-1.4 mean change from baseline Standard Deviation 4.68	-1.5 mean change from baseline Standard Deviation 5.05	-1.3 mean change from baseline Standard Deviation 4.07	—	—	—
Secondary Efficacy Endpoints Week 13 ADCS-ADL-SIV : FAS	-0.7 mean change from baseline Standard Deviation 4.59	-1.0 mean change from baseline Standard Deviation 4.86	-2.2 mean change from baseline Standard Deviation 5.28	—	—	—
Secondary Efficacy Endpoints Week 9 MMSE-2: FAS	0.8 mean change from baseline Standard Deviation 2.98	0.3 mean change from baseline Standard Deviation 3.01	0.5 mean change from baseline Standard Deviation 3.11	—	—	—
Secondary Efficacy Endpoints Week 13 MMSE-2: FAS	0.5 mean change from baseline Standard Deviation 3.09	0.3 mean change from baseline Standard Deviation 2.54	-0.2 mean change from baseline Standard Deviation 3.49	—	—	—
Secondary Efficacy Endpoints SIB Week 5 Full Analysis Set	1.5 mean change from baseline Standard Deviation 7.36	-0.8 mean change from baseline Standard Deviation 6.55	-1.2 mean change from baseline Standard Deviation 10.31	—	—	—
Secondary Efficacy Endpoints SIB Week 5 Completer Analysis Set	1.7 mean change from baseline Standard Deviation 6.02	0.1 mean change from baseline Standard Deviation 5.93	-1.9 mean change from baseline Standard Deviation 10.33	—	—	—
Secondary Efficacy Endpoints SIB Week 9 Full Analysis Set	1.3 mean change from baseline Standard Deviation 6.87	-0.2 mean change from baseline Standard Deviation 6.41	-0.0 mean change from baseline Standard Deviation 9.91	—	—	—
Secondary Efficacy Endpoints SIB Week 9 Completer Analysis Set	1.2 mean change from baseline Standard Deviation 6.93	-0.1 mean change from baseline Standard Deviation 6.06	-0.1 mean change from baseline Standard Deviation 10.0	—	—	—
Secondary Efficacy Endpoints Week 5 ADCS-ADL-SIV : FAS	-0.3 mean change from baseline Standard Deviation 4.16	-1.1 mean change from baseline Standard Deviation 6.31	-0.7 mean change from baseline Standard Deviation 5.07	—	—	—
Secondary Efficacy Endpoints Week 5 MMSE-2: FAS	0.4 mean change from baseline Standard Deviation 2.43	-0.1 mean change from baseline Standard Deviation 2.79	-0.1 mean change from baseline Standard Deviation 2.40	—	—	—
Secondary Efficacy Endpoints Week 5 Neuropsychiatric Inventory (NPI): FAS	-0.5 mean change from baseline Standard Deviation 11.72	1.7 mean change from baseline Standard Deviation 12.03	-2.4 mean change from baseline Standard Deviation 10.31	—	—	—
Secondary Efficacy Endpoints Week 9 Neuropsychiatric Inventory (NPI): FAS	0.5 mean change from baseline Standard Deviation 11.97	2.0 mean change from baseline Standard Deviation 8.33	-2.5 mean change from baseline Standard Deviation 11.05	—	—	—
Secondary Efficacy Endpoints Week 13 Neuropsychiatric Inventory (NPI): FAS	1.0 mean change from baseline Standard Deviation 12.62	2.0 mean change from baseline Standard Deviation 11.94	1.0 mean change from baseline Standard Deviation 10.45	—	—	—

POST_HOC outcome

Timeframe: Assessments at weeks 5, 9, 13, and 30 days after end of treatment (up to day 107).

Population: Participants in the 3 treatment groups were further sorted by use of memantine. The number of participants in each category at each timepoint is noted. Attrition occurred through the course of the study.

Change from baseline in SIB score was compared between subjects receiving concurrent treatment with memantine and subjects not being treated with memantine.

Outcome measures

Outcome measures
Measure	Bryostatin 1 20ug n=26 Participants Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug n=37 Participants Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo n=31 Participants Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 20ug Without Memantine n=18 Participants Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	Bryostatin 1 40ug Without Memantine n=8 Participants Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks.	Placebo Without Memantine n=15 Participants Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks.
Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline Week 5 SIB change from Baseline	0.1 mean change from baseline in SIB score Standard Deviation 8.11	-1.6 mean change from baseline in SIB score Standard Deviation 6.50	-1.3 mean change from baseline in SIB score Standard Deviation 10.50	3.4 mean change from baseline in SIB score Standard Deviation 5.75	3.9 mean change from baseline in SIB score Standard Deviation 4.98	-1.2 mean change from baseline in SIB score Standard Deviation 10.26
Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline Week 9 SIB change from Baseline	-0.1 mean change from baseline in SIB score Standard Deviation 6.52	-0.6 mean change from baseline in SIB score Standard Deviation 6.88	-0.4 mean change from baseline in SIB score Standard Deviation 11.01	3.5 mean change from baseline in SIB score Standard Deviation 7.04	2.0 mean change from baseline in SIB score Standard Deviation 3.16	0.8 mean change from baseline in SIB score Standard Deviation 7.44
Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline Week 13 SIB change from Baseline	-0.5 mean change from baseline in SIB score Standard Deviation 6.51	-0.1 mean change from baseline in SIB score Standard Deviation 6.61	-0.5 mean change from baseline in SIB score Standard Deviation 10.03	4.5 mean change from baseline in SIB score Standard Deviation 7.01	3.9 mean change from baseline in SIB score Standard Deviation 5.84	-1.1 mean change from baseline in SIB score Standard Deviation 6.89
Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline 30-day Followup SIB change from Baseline	-1.1 mean change from baseline in SIB score Standard Deviation 8.39	0.3 mean change from baseline in SIB score Standard Deviation 7.71	-3.8 mean change from baseline in SIB score Standard Deviation 13.10	6.7 mean change from baseline in SIB score Standard Deviation 5.58	4.0 mean change from baseline in SIB score Standard Deviation 5.66	-1.0 mean change from baseline in SIB score Standard Deviation 8.31

Adverse Events

Bryostatin 1 20ug

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Bryostatin 1 40ug

Serious events: 6 serious events

Other events: 46 other events

Deaths: 1 deaths

Placebo

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Bryostatin 1 20ug n=46 participants at risk Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug n=47 participants at risk Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo n=48 participants at risk Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/47 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/48 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/47 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/48 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Nervous system disorders Confusion postoperative	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/47 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/48 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/47 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/48 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Cardiac disorders Atrial fibrillation	2.2% 1/46 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/47 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
General disorders Infusion Site Pain	2.2% 1/46 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/47 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Nervous system disorders Dementia Alzheimer's Type	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/47 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/47 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Infections and infestations Infusion site cellulitis	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	4.3% 2/47 • Number of events 2 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Nervous system disorders Seizure	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/47 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Nervous system disorders Syncope	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/47 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.

Other adverse events

Other adverse events
Measure	Bryostatin 1 20ug n=46 participants at risk Bryostatin 20 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 24 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Bryostatin 1 40ug n=47 participants at risk Bryostatin 40 micrograms administered IV over 45 minutes every other week after 2 initial loading doses of 48 micrograms administered weekly. A total of 7 doses administered over 12 weeks. Bryostatin 1: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.	Placebo n=48 participants at risk Placebo administered IV over 45 minutes every other week after 2 initial doses administered weekly. A total of 7 doses administered over 12 weeks. Placebo: The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
Musculoskeletal and connective tissue disorders Myalgia	2.2% 1/46 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	8.5% 4/47 • Number of events 6 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Gastrointestinal disorders Diarrhea	10.9% 5/46 • Number of events 6 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	10.6% 5/47 • Number of events 5 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/48 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
General disorders Infusion site extravasation	6.5% 3/46 • Number of events 3 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	6.4% 3/47 • Number of events 4 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
General disorders Fatigue	2.2% 1/46 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	10.6% 5/47 • Number of events 5 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
General disorders Infusion site pain	6.5% 3/46 • Number of events 3 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/47 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/48 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Infections and infestations Urinary tract infection	4.3% 2/46 • Number of events 2 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	6.4% 3/47 • Number of events 3 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	8.3% 4/48 • Number of events 4 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Infections and infestations Infusion site cellulitis	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	8.5% 4/47 • Number of events 4 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Injury, poisoning and procedural complications Fall	2.2% 1/46 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	8.5% 4/47 • Number of events 5 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	2.1% 1/48 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Injury, poisoning and procedural complications Contusion	2.2% 1/46 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	6.4% 3/47 • Number of events 3 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Investigations Weight decreased	0.00% 0/46 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	10.6% 5/47 • Number of events 5 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	0.00% 0/48 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Metabolism and nutrition disorders Decreased appetite	2.2% 1/46 • Number of events 1 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	12.8% 6/47 • Number of events 6 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	4.2% 2/48 • Number of events 2 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.
Nervous system disorders Headache	6.5% 3/46 • Number of events 4 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	8.5% 4/47 • Number of events 4 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.	6.2% 3/48 • Number of events 3 • Adverse event data was collected beginning at the time of informed consent until the 30-day post treatment visit. For subjects enrolled under protocol versions 1 (17 Apr 2015) and 2 (20 Jan 2016), this collection occurred from Day -21 through Day 198 for subjects completing the study. For subjects enrolled under protocol version 3 (15 Jul 2016) this collection occurred from Day -28 through Day 105. In addition to the standard defined adverse events, an adverse event of special interest was defined in this study; myalgia.

Additional Information

David Crockford, Vice President, Regulatory Affairs

Neurotrope BioScience, Inc.

Phone: (973)242-0005

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60