Clinical trial NCT02221947: Study to Evaluate the Preliminary Safety, Efficacy, PK and PD of Bryostatin 1 in Patients With Alzheimer's Disease
Official title: A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Preliminary Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Bryostatin 1 in Patients With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Alzheimer's Disease
Keywords: Alzheimer's
bryostatin
PKC epsilon
Lead sponsor: Neurotrope Bioscience, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Blanchette Rockefeller Neurosciences Insitute
First posted: 2014-08-21
Enrollment: 9
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is being done to evaluate the safety, tolerability and potential effectiveness of a new investigational drug, bryostatin 1, in patients with Alzheimer's disease (AD).

Detailed description: This study is a single center, randomized, double-blind, placebo-controlled, parallel groups trial in patients with AD. Each subject enrolled in the trial will be randomized to receive a single IV dose of 0 (placebo) or 25 μg/m2 bryostatin. A total of 15 subjects (5 in the placebo arm and 10 in the treatment arm) will be enrolled in the study. The study consists of screening evaluations and on study evaluations divided into two segments, an inpatient segment and an outpatient segment. The four-day inpatient segment will consist of baseline evaluations and a 1-hour IV infusion of study drug followed by evaluations at multiple evaluations over the first 72 hrs post dose. During the outpatient segment, patients will be followed for AEs and have a final evaluation at 2 weeks post dose and a 4-week telephone safety follow up. Evaluations will include safety, efficacy, pharmacokinetics, and pharmacodynamics as assessed by PKC activity

Eligibility criteria: Inclusion Criteria:

* Male or female, age 50 - 85 yrs. Females are non-childbearing potential
* Patient must have a cognitive deficit present for at least 1 year and meet diagnostic criteria for probable Alzheimer's Disease Dementia by NIA-AA criteria or prodromal Alzheimer's Disease
* Mini Mental State Exam score of 16-26
* Ability to walk, at least with an assistive device
* Vision and hearing sufficient to comply with testing
* Normal cognitive and social functioning prior to onset of dementia, with evidence of progressive symptoms from patient or informant
* Consistent caregiver to accompany patient to visits
* Sufficient basic education to be able to complete the cognitive assessments
* Living outside an institution

Exclusion Criteria:

* Dementia due to any condition other than AD, including vascular dementia
* Significant neuroimaging abnormalities, previously known or discovered on screening MRI scan,
* Evidence of clinically significant unstable cardiovascular, renal, hepatic, gastrointestinal, neurological, or metabolic disease within the past 6 months
* Use of any drug within 14 days prior to randomization unless the dose of the drug and the condition being treated have been stable for at least 30 days and are expected to remain stable during the study
* Use of tobacco products or nicotine-containing products within 3 months before Day 1
* Use of high dose vitamin E, or valproic acid
* Any medical or psychiatric condition that may require medication or surgical treatment during the study
* Life expectancy less than 6 months
* Use of an investigational drug within 2 months prior to the screening visit
* Clinically significant neurological disease other than AD
* Major depression, alcohol or drug dependence or suicidality
* Psychotic episodes requiring hospitalization or antipsychotic therapy for more than 2 weeks within the past 10 years, not linked to AD
* Agitation sufficient to preclude participation in this trial
* Epilepsy or anti-epileptic drug therapy
* Abnormal laboratory tests that might point to another etiology for dementia;
* Acute or poorly controlled medical illness
* Likelihood, according to clinical judgment, of being transferred to a nursing home within 6 months

Primary outcomes:
measure: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
timeFrame: Within 2 weeks of study drug dosing
measure: Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
timeFrame: 48 hours post start of study drug infusion
Secondary outcomes:
measure: Preliminary Efficacy of a Single Dose of Bryostatin in the Treatment of Patients With AD
timeFrame: Specified timepoints within 2 weeks post study drug infusion
Other outcomes:
measure: Pharmacokinetic Parameters of Bryostatin.
timeFrame: Bryostatin plasma concentration pre-dose and at 15 min, 30 min, 1 hr, 1.5 hr, 2hr, 3hr and 6rs post dose.
Locations:
city: Glendale
country: United States
facility: California Clinical Trials Medical Center
state: California
Study officials:
affiliation: California Clinical Trials Medical Group
name: Hakop Gevorkyan, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References: