Alzheimer's Disease
Conditions
Brief summary
This is a randomized double-blind placebo-controlled study comparing different doses of bryostatin for the treatment of moderately severe to severe Alzheimer's disease. The study is 15 weeks in duration, including a safety and efficacy evaluation 30 days after the last dose of study drug.
Detailed description
This study will enroll 150 moderately severe to severe Alzheimer's disease subjects. Subjects will be randomly assigned 1:1:1 to treatment with two different doses of bryostatin 1 or placebo. The primary analysis will take place after 12 weeks of treatment (7 doses).
Interventions
DRUGBryostatin 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.
OTHERPlacebo
The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
Sponsors
Neurotrope Bioscience, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent from caregiver and subject (if possible) or legally acceptable representative if different from caregiver * Male and female subjects 55-85 years of age inclusive * Cognitive deficit present for at least 2 years that meet the diagnostic criteria for probable Alzheimer's * Mini Mental State Exam (MMSE-2) score of 4-15 * Patients must be able to perform at least one item on the Severe Impairment Battery Scale * Neuroimaging (computerized tomography (CT) or Magnetic Resonance Imaging (MRI)) within the last 24 months consistent with a diagnosis of probable Alzheimer's disease (AD) * Reliable caregiver(s) or informant(s) who attends the subject at least an average of 3 hours or more per day for 3 or more days per week * Adequate vision and motor function to comply with testing * If taking drugs approved for treatment of Alzheimer's disease (e.g. cholinesterase inhibitors, memantine), must be on a stable dose for at least 3 months prior to entry into study and the dose must not change during the study unless a change is required due to an adverse event or a clinically significant change in the patient's status.
Exclusion criteria
* Dementia due to any condition other than AD, including vascular dementia (Rosen-modified Hachinski lschemic score ≥ 5) * Evidence of significant central nervous system (CNS) vascular disease on previous neuroimaging including but not limited to: cortical stroke, multiple infarcts, localized single infarcts in the thalamus, angular gyrus, multiple lacunar infarcts or extensive white matter injury * Clinically significant neurologic disease or condition other than AD, such as cerebral tumor, chronic subdural fluid collections, Huntington's Disease, Parkinson's Disease, normal pressure hydrocephalus, or any other diagnosis that could interfere with assessment of safety and efficacy * Evidence of clinically significant unstable cardiovascular, pulmonary, renal, hepatic, gastrointestinal, neurologic, or metabolic disease within the 6 months prior to enrollment * Poorly controlled diabetes, at the discretion of the Principal Investigator * Creatinine clearance (CL) of \<45ml/min * Use of an active Alzheimer's vaccine within 2 years prior to screening * Use of a monoclonal antibody for treatment of AD within 1 year prior to screening * Any medical or psychiatric condition that is likely to require initiation of additional medication or surgical intervention during the course of the study * Use of an investigational drug within 30 days prior to screening * Prior exposure to bryostatin, or known sensitivity to bryostatin or any ingredient in the study drug * Any other concurrent medical condition, which in the opinion of the PI makes the subject unsuitable for the clinical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | Baseline through 30 days post end of treatment (up to Day 107) | Evaluations of adverse events (AEs), serious adverse events (SAEs), Adverse event of special interest - myalgia |
| Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | Primary analysis at Week 13 (day 91) after 12 weeks of treatment (up to day 107) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Efficacy Endpoints | Week 5, Week 9, Week 13 | * 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. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 46 |
| 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. | 47 |
| 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. | 48 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 4 | 5 |
| Overall Study | noncompliance, investigator termination, | 2 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 12 | 2 |
Baseline characteristics
| Characteristic | Bryostatin 1 20ug | Bryostatin 1 40ug | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 71.2 years STANDARD_DEVIATION 8.4 | 70.2 years STANDARD_DEVIATION 7.53 | 73.5 years STANDARD_DEVIATION 7.68 | 71.7 years STANDARD_DEVIATION 7.94 |
| Mini Mental State Exam version 2 (MMSE-2) baseline score 10-15 | 28 Participants | 27 Participants | 29 Participants | 84 Participants |
| Mini Mental State Exam-version 2 (MMSE-2) baseline scores 4-9 | 18 Participants | 20 Participants | 19 Participants | 57 Participants |
| Race/Ethnicity, Customized African American | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 42 Participants | 46 Participants | 45 Participants | 133 Participants |
| Region of Enrollment United States | 46 participants | 47 participants | 48 participants | 141 participants |
| Sex: Female, Male Female | 26 Participants | 22 Participants | 23 Participants | 71 Participants |
| Sex: Female, Male Male | 20 Participants | 25 Participants | 25 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 1 / 47 | 0 / 48 |
| other Total, other adverse events | 21 / 46 | 46 / 47 | 12 / 48 |
| serious Total, serious adverse events | 2 / 46 | 6 / 47 | 4 / 48 |
Outcome results
Primary
Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bryostatin 1 20ug | 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 7.1 |
| Bryostatin 1 20ug | 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 7.1 |
| Bryostatin 1 20ug | 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 |
| Bryostatin 1 20ug | 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 |
| Bryostatin 1 40ug | Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | 30-Day Followup Completer Analysis Set | 0.9 mean change from baseline in SIB score | Standard Deviation 7.85 |
| Bryostatin 1 40ug | Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | Week 13 Full Analysis Set (FAS) | 0.8 mean change from baseline in SIB score | Standard Deviation 6.58 |
| Bryostatin 1 40ug | Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | 30-Day Followup Full Analysis Set | 0.6 mean change from baseline in SIB score | Standard Deviation 7.51 |
| Bryostatin 1 40ug | Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | Week 13 Completer Analysis Set (CAS) | 0.8 mean change from baseline in SIB score | Standard Deviation 6.58 |
| Placebo | Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | 30-Day Followup Completer Analysis Set | -2.7 mean change from baseline in SIB score | Standard Deviation 11.44 |
| Placebo | Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | Week 13 Completer Analysis Set (CAS) | -0.7 mean change from baseline in SIB score | Standard Deviation 9.02 |
| Placebo | Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | 30-Day Followup Full Analysis Set | -2.7 mean change from baseline in SIB score | Standard Deviation 11.44 |
| Placebo | Efficacy: Change From Baseline in Severe Impairment Battery (SIB) in the Full Analysis Set (FAS) | Week 13 Full Analysis Set (FAS) | -0.4 mean change from baseline in SIB score | Standard Deviation 9.02 |
Comparison: The primary statistical objective for efficacy was to estimate the effect of bryostatin on the mean change in the Severe Impairment Battery (SIB) after 12 weeks of treatment. A linear model was used for both estimation and significance testing. Primary analysis populations were defined as the Full Analysis Set (FAS) and the Completer Analysis Set (CAS)p-value: <0.1t-test, 1 sided
Comparison: Change from baseline in SIB in the Completer Analysis Set (CAS)p-value: <0.1t-test, 1 sided
Primary
Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events
Evaluations of adverse events (AEs), serious adverse events (SAEs), Adverse event of special interest - myalgia
Time frame: Baseline through 30 days post end of treatment (up to Day 107)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bryostatin 1 20ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | Number of Subjects w Treatment Emergent AE (TEAE) | 30 participants |
| Bryostatin 1 20ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Treatment Related TEAE | 17 participants |
| Bryostatin 1 20ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w TEAE leading to treatment discont. | 1 participants |
| Bryostatin 1 20ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Serious TEAE | 1 participants |
| Bryostatin 1 20ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Treatment Related Serious TEAE | 1 participants |
| Bryostatin 1 20ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Treatment Emergent Myalgia | 1 participants |
| Bryostatin 1 20ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Serious Treatment Emergent Myalgia | 0 participants |
| Bryostatin 1 20ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Fatal TEAE | 0 participants |
| Bryostatin 1 40ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w TEAE leading to treatment discont. | 3 participants |
| Bryostatin 1 40ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Serious Treatment Emergent Myalgia | 0 participants |
| Bryostatin 1 40ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Serious TEAE | 6 participants |
| Bryostatin 1 40ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Treatment Related Serious TEAE | 4 participants |
| Bryostatin 1 40ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Treatment Emergent Myalgia | 4 participants |
| Bryostatin 1 40ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | Number of Subjects w Treatment Emergent AE (TEAE) | 39 participants |
| Bryostatin 1 40ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Treatment Related TEAE | 24 participants |
| Bryostatin 1 40ug | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Fatal TEAE | 1 participants |
| Placebo | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w TEAE leading to treatment discont. | 2 participants |
| Placebo | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Treatment Related TEAE | 8 participants |
| Placebo | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | Number of Subjects w Treatment Emergent AE (TEAE) | 28 participants |
| Placebo | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Serious TEAE | 3 participants |
| Placebo | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Serious Treatment Emergent Myalgia | 0 participants |
| Placebo | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects w Treatment Emergent Myalgia | 0 participants |
| Placebo | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Treatment Related Serious TEAE | 0 participants |
| Placebo | Safety: Number of Subjects With Treatment-emergent Adverse Events and Serious Adverse Events | # of Subjects with Fatal TEAE | 0 participants |
Secondary
Secondary Efficacy Endpoints
* 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.
Time frame: Week 5, Week 9, Week 13
Population: The number of participants analyzed over the course of the study diminished as a result of attrition.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 9 Neuropsychiatric Inventory (NPI): FAS | 0.5 mean change from baseline | Standard Deviation 11.97 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 9 MMSE-2: FAS | 0.8 mean change from baseline | Standard Deviation 2.98 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 9 ADCS-ADL-SIV : FAS | -1.4 mean change from baseline | Standard Deviation 4.68 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | SIB Week 9 Full Analysis Set | 1.3 mean change from baseline | Standard Deviation 6.87 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 5 MMSE-2: FAS | 0.4 mean change from baseline | Standard Deviation 2.43 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 13 ADCS-ADL-SIV : FAS | -0.7 mean change from baseline | Standard Deviation 4.59 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | SIB Week 5 Full Analysis Set | 1.5 mean change from baseline | Standard Deviation 7.36 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | SIB Week 5 Completer Analysis Set | 1.7 mean change from baseline | Standard Deviation 6.02 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 5 Neuropsychiatric Inventory (NPI): FAS | -0.5 mean change from baseline | Standard Deviation 11.72 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | SIB Week 9 Completer Analysis Set | 1.2 mean change from baseline | Standard Deviation 6.93 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 13 Neuropsychiatric Inventory (NPI): FAS | 1.0 mean change from baseline | Standard Deviation 12.62 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 13 MMSE-2: FAS | 0.5 mean change from baseline | Standard Deviation 3.09 |
| Bryostatin 1 20ug | Secondary Efficacy Endpoints | Week 5 ADCS-ADL-SIV : FAS | -0.3 mean change from baseline | Standard Deviation 4.16 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 13 ADCS-ADL-SIV : FAS | -1.0 mean change from baseline | Standard Deviation 4.86 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | SIB Week 5 Full Analysis Set | -0.8 mean change from baseline | Standard Deviation 6.55 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | SIB Week 5 Completer Analysis Set | 0.1 mean change from baseline | Standard Deviation 5.93 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | SIB Week 9 Full Analysis Set | -0.2 mean change from baseline | Standard Deviation 6.41 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | SIB Week 9 Completer Analysis Set | -0.1 mean change from baseline | Standard Deviation 6.06 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 5 ADCS-ADL-SIV : FAS | -1.1 mean change from baseline | Standard Deviation 6.31 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 9 ADCS-ADL-SIV : FAS | -1.5 mean change from baseline | Standard Deviation 5.05 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 5 MMSE-2: FAS | -0.1 mean change from baseline | Standard Deviation 2.79 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 9 MMSE-2: FAS | 0.3 mean change from baseline | Standard Deviation 3.01 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 13 MMSE-2: FAS | 0.3 mean change from baseline | Standard Deviation 2.54 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 5 Neuropsychiatric Inventory (NPI): FAS | 1.7 mean change from baseline | Standard Deviation 12.03 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 9 Neuropsychiatric Inventory (NPI): FAS | 2.0 mean change from baseline | Standard Deviation 8.33 |
| Bryostatin 1 40ug | Secondary Efficacy Endpoints | Week 13 Neuropsychiatric Inventory (NPI): FAS | 2.0 mean change from baseline | Standard Deviation 11.94 |
| Placebo | Secondary Efficacy Endpoints | Week 9 MMSE-2: FAS | 0.5 mean change from baseline | Standard Deviation 3.11 |
| Placebo | Secondary Efficacy Endpoints | SIB Week 9 Completer Analysis Set | -0.1 mean change from baseline | Standard Deviation 10 |
| Placebo | Secondary Efficacy Endpoints | Week 9 Neuropsychiatric Inventory (NPI): FAS | -2.5 mean change from baseline | Standard Deviation 11.05 |
| Placebo | Secondary Efficacy Endpoints | Week 13 MMSE-2: FAS | -0.2 mean change from baseline | Standard Deviation 3.49 |
| Placebo | Secondary Efficacy Endpoints | SIB Week 9 Full Analysis Set | -0.0 mean change from baseline | Standard Deviation 9.91 |
| Placebo | Secondary Efficacy Endpoints | SIB Week 5 Full Analysis Set | -1.2 mean change from baseline | Standard Deviation 10.31 |
| Placebo | Secondary Efficacy Endpoints | Week 5 Neuropsychiatric Inventory (NPI): FAS | -2.4 mean change from baseline | Standard Deviation 10.31 |
| Placebo | Secondary Efficacy Endpoints | Week 13 ADCS-ADL-SIV : FAS | -2.2 mean change from baseline | Standard Deviation 5.28 |
| Placebo | Secondary Efficacy Endpoints | Week 9 ADCS-ADL-SIV : FAS | -1.3 mean change from baseline | Standard Deviation 4.07 |
| Placebo | Secondary Efficacy Endpoints | SIB Week 5 Completer Analysis Set | -1.9 mean change from baseline | Standard Deviation 10.33 |
| Placebo | Secondary Efficacy Endpoints | Week 5 MMSE-2: FAS | -0.1 mean change from baseline | Standard Deviation 2.4 |
| Placebo | Secondary Efficacy Endpoints | Week 5 ADCS-ADL-SIV : FAS | -0.7 mean change from baseline | Standard Deviation 5.07 |
| Placebo | Secondary Efficacy Endpoints | Week 13 Neuropsychiatric Inventory (NPI): FAS | 1.0 mean change from baseline | Standard Deviation 10.45 |
Post Hoc
Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline
Change from baseline in SIB score was compared between subjects receiving concurrent treatment with memantine and subjects not being treated with memantine.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bryostatin 1 20ug | 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 |
| Bryostatin 1 20ug | 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 |
| Bryostatin 1 20ug | 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 |
| Bryostatin 1 20ug | 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 |
| Bryostatin 1 40ug | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 13 SIB change from Baseline | -0.1 mean change from baseline in SIB score | Standard Deviation 6.61 |
| Bryostatin 1 40ug | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 9 SIB change from Baseline | -0.6 mean change from baseline in SIB score | Standard Deviation 6.88 |
| Bryostatin 1 40ug | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 5 SIB change from Baseline | -1.6 mean change from baseline in SIB score | Standard Deviation 6.5 |
| Bryostatin 1 40ug | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | 30-day Followup SIB change from Baseline | 0.3 mean change from baseline in SIB score | Standard Deviation 7.71 |
| Placebo | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | 30-day Followup SIB change from Baseline | -3.8 mean change from baseline in SIB score | Standard Deviation 13.1 |
| Placebo | 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 10.03 |
| Placebo | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 9 SIB change from Baseline | -0.4 mean change from baseline in SIB score | Standard Deviation 11.01 |
| Placebo | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 5 SIB change from Baseline | -1.3 mean change from baseline in SIB score | Standard Deviation 10.5 |
| Bryostatin 1 20ug Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 5 SIB change from Baseline | 3.4 mean change from baseline in SIB score | Standard Deviation 5.75 |
| Bryostatin 1 20ug Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | 30-day Followup SIB change from Baseline | 6.7 mean change from baseline in SIB score | Standard Deviation 5.58 |
| Bryostatin 1 20ug Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 9 SIB change from Baseline | 3.5 mean change from baseline in SIB score | Standard Deviation 7.04 |
| Bryostatin 1 20ug Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 13 SIB change from Baseline | 4.5 mean change from baseline in SIB score | Standard Deviation 7.01 |
| Bryostatin 1 40ug Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 13 SIB change from Baseline | 3.9 mean change from baseline in SIB score | Standard Deviation 5.84 |
| Bryostatin 1 40ug Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | 30-day Followup SIB change from Baseline | 4.0 mean change from baseline in SIB score | Standard Deviation 5.66 |
| Bryostatin 1 40ug Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 9 SIB change from Baseline | 2.0 mean change from baseline in SIB score | Standard Deviation 3.16 |
| Bryostatin 1 40ug Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 5 SIB change from Baseline | 3.9 mean change from baseline in SIB score | Standard Deviation 4.98 |
| Placebo Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 9 SIB change from Baseline | 0.8 mean change from baseline in SIB score | Standard Deviation 7.44 |
| Placebo Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 13 SIB change from Baseline | -1.1 mean change from baseline in SIB score | Standard Deviation 6.89 |
| Placebo Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | 30-day Followup SIB change from Baseline | -1.0 mean change from baseline in SIB score | Standard Deviation 8.31 |
| Placebo Without Memantine | Severe Impairment Battery (SIB) Scores by Memantine Use at Baseline | Week 5 SIB change from Baseline | -1.2 mean change from baseline in SIB score | Standard Deviation 10.26 |