Study of the Pharmacokinetics and Pharmacodynamics of POSIPHEN® in Subjects With Amnestic Mild Cognitive Impairment

An Open-Label, Two-Stage Study to Evaluate the Pharmacokinetics and Pharmacodynamics of POSIPHEN® in Plasma and CSF After a 10-Day Treatment Period in Subjects With Amnestic Mild Cognitive Impairment

This trial will determine the pharmacokinetics of Posiphen® in both plasma and CSF after a 10-day treatment period with Posiphen® in subjects with amnestic MCI. The effects of this treatment on biomarkers will also be determined in CSF, whole blood, and plasma or serum as primary pharmacodynamic (PD) objectives.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease; Amnestic Mild Cognitive Impairment
• Intervention / Treatment: Drug: Posiphen® tartrate capsules

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • CEDRA Clinical Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or post-menopausal females aged 55 to 80 years, inclusive.
2. Must have Mild Cognitive Impairment (MCI) (amnestic subtype) according to Petersen's criteria (2004).
3. Mini Mental Status Examination (MMSE) score should be ≥24.
4. Must score below a pre-determined cut-off score on the logical memory II delayed paragraph recall sub-test of the Wechsler Memory Scale Revised (WMS-R).
5. Must have a Clinical Dementia Rating of 0.5 with a memory box score of 0.5 or 1.0.
6. Modified Hachinski score of less than or equal to 4.
7. Hamilton Depression rating scale (HAMD17) score of less than or equal to 12 with a score of 0 on items 1, 2, and 3 (depressed mood, feelings of guilt, and suicidal ideation).
8. No evidence of current suicidal ideation or previous suicide attempt in past 2 years as evaluated in the Columbia Suicidality Checklist.
9. MRI scans within 12 months prior to screening, or per screening MRI, without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease.
10. No clinically significant abnormalities in the lumbar spine should be present on a lumbar X-ray that would contraindicate lumbar puncture.
11. Adequate visual and hearing ability (physical ability to perform all the study assessments).
12. Normal B12, folic acid, and thyroid function tests (thyroid stimulating hormone [TSH], free T4, and free T3).
13. Do not require nursing home care.

Exclusion Criteria:

1. Any significant neurologic disease other than amnestic MCI, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
2. Major depression, schizophrenia or another major psychiatric disorder as described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) within the past 2 years.
3. Psychotic features, agitation, or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
4. History of alcohol or substance abuse or dependence within the past 2 years.
5. Subjects with any febrile illness within 1 week prior to the CSF collection.
6. Subjects who have history of migraine headaches and any other type of headaches of at least moderate severity more than twice per month.
7. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol or pose potential risk to the subjects.
8. Use of medications prohibited by the study.
9. Any clinically significant laboratory abnormalities.
10. Subjects with infection or inflammation of the skin or skin disease at or in proximity to the lumbar puncture site.
11. History of lumbar spine surgery or chronic low back pain (CLBP).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Posiphen® tartrate capsules	Drug: Posiphen® tartrate capsules; Capsules administered (240 mg/day) for 10 days Capsules administered (160 mg/day) for 10 days; Other Names: Posiphen® Tartrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics	To determine the pharmacokinetics (PK) of Posiphen® and its metabolites in plasma and CSF after a 10-day treatment period with Posiphen®.	10 days
Pharmacodynamics	To assess the effects of a 10-day treatment period with Posiphen® on the levels of amyloid precursor protein (APP), amyloid β protein 40 (Aβ40), amyloid β protein 42 (Aβ42), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) in plasma and CSF from subjects with amnestic MCI.	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	To assess the effects of a 10-day treatment period with Posiphen® on the levels of amino terminal fragment (N-APP), tau (T-tau), phosphorylated tau (P-tau), nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), interleukin 1B (IL1B), S-100B protein (S-100B) in plasma or serum and CSF, and the activities of AChE and BChE in whole blood or plasma and CSF from subjects with amnestic MCI.	10 days
Safety	To determine the safety and tolerability of a 10-day treatment period with Posiphen®.	10 days

Collaborators and Investigators

• Sponsor: Annovis Bio Inc.
• Investigators: Principal Investigator: Mark T Leibowitz, MD, CEDRA

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ACTUAL): July 1, 2010
• Study Completion (ACTUAL): July 1, 2010

Study Registration Dates

• First Submitted: February 19, 2010
• First Submitted That Met QC Criteria: February 19, 2010
• First Posted (ESTIMATE): February 22, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 22, 2015
• Last Update Submitted That Met QC Criteria: April 20, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Biomarkers; Pharmacodynamics; Alzheimer's; Amnestic Mild Cognitive Impairment
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Cholinesterase Inhibitors; Phenserine
• Other Study ID Numbers: QR 12001