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Trial record 28 of 460 for:    Recruiting, Not yet recruiting, Available Studies | "Alzheimer Disease"

Safety, Tolerability, PK and PD of Posiphen® in Subjects With Early Alzheimer's Disease (DISCOVER)

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ClinicalTrials.gov Identifier: NCT02925650
Recruitment Status : Recruiting
First Posted : October 6, 2016
Last Update Posted : October 15, 2018
Sponsor:
Collaborator:
Alzheimer's Disease Cooperative Study (ADCS)
Information provided by (Responsible Party):
QR Pharma Inc.

Brief Summary:
This study evaluates the safety and pharmacological effects of 3 different doses of Posiphen® when compared to a placebo, in adult male and female patients with early Alzheimer's disease (AD).

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: Posiphen Drug: Placebo Phase 1 Phase 2

Detailed Description:
Posiphen®, which was discovered by the US National Institute on Aging (NIA) is a small, orally active, experimental drug that specifically inhibits the synthesis of amyloid precursor protein (APP), Tau and α-Synuclein. It is distinct from other Alzheimer's disease drugs currently in development, because it inhibits the formation of several toxic proteins, rather than removing individual toxic protein after they are produced. Posiphen has potential utility as a disease modifying treatment for AD. The present study will confirm the pharmacokinetics (PK) of Posiphen and its metabolites in plasma and cerebral spinal fluid (CSF). It will also measure the effects of a 23-25 day treatment period with Posiphen on the CSF and plasma levels of a number of biomarkers, inflammatory factors and control proteins. It will also expand the safety data in humans by extending the treatment period from 10 days to a treatment period from 23-25 days. In addition, this study will measure concentrations of various soluble biomarkers in CSF and use the SILK™ assay methods to directly measure the effect of Posiphen on the fractional synthesis rate of Aβ40 in CSF, which will help guide the further development of Posiphen and determine the feasibility of SILK™ in a multicenter trial.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamic (PD) Effects of Posiphen® in Subjects With Early Alzheimer's Disease (AD)
Actual Study Start Date : March 2, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Low Dose
The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days.
Drug: Posiphen
oral solid dosage form capsule

Experimental: Medium Dose
The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days.
Drug: Posiphen
oral solid dosage form capsule

Experimental: High Dose
The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days.
Drug: Posiphen
oral solid dosage form capsule

Placebo Comparator: Placebo
The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days.
Drug: Placebo
oral solid dosage form capsule




Primary Outcome Measures :
  1. Safety and Tolerability: Reports of adverse events or study discontinuations [ Time Frame: up to 25 days ]
    Reports of adverse events or study discontinuations related to Posiphen

  2. AUC of Posiphen and its metabolites in plasma and CSF [ Time Frame: up to 25 days ]
    The levels of Posiphen and its metabolites will be determined in plasma and CSF

  3. Fractional synthesis rate of Aβ40 in CSF using the SILK™ technique [ Time Frame: up to 25 days ]
    The fractional synthesis rate (FSR) of Aβ40 will be measured in the CSF using the SILK™ technique


Secondary Outcome Measures :
  1. Concentration of soluble biomarkers of Alzheimer's disease in CSF [ Time Frame: up to 25 days ]
    Alzheimer's disease biomarkers including Beta Amyloid 38 (Aβ38), Aβ42, Soluble Amyloid Precursor Protein alpha (sAPPα), Soluble Amyloid Precursor Protein beta (sAPPβ), T-Tau, and Acetylcholinesterase (AChE), will be measured in the CSF to determine if Posiphen has any affect.

  2. Assessment of cognitive assessments [ Time Frame: up to 25 days ]
    The short-term cognitive effects of Posiphen will be measured using the Alzheimer's Disease Assessment Scale (ADAS-Cog12).

  3. Assessment of mental status effects [ Time Frame: up to 25 days ]
    The short-term mental status effects of Posiphen will be measured using the Mini-Mental State Examination (MMSE).

  4. Assessment of neuropsychiatric effects [ Time Frame: up to 25 days ]
    The short-term neuropsychiatric effects of Posiphen will be measured using the Neuropsychiatric Inventory (NPI).



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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female aged 55 to 85 years (inclusive).
  2. Female participants must be post-menopausal for at least 2 consecutive years or surgically sterile (bilateral tubal ligation, hysterectomy or bilateral oophorectomy) for at least 6 months prior to screening.
  3. Female participants will be given a urine pregnancy test at the screening visit for which they should test negative.
  4. Diagnosis of amnestic MCI or probable mild AD according to the core clinical criteria outlined in the NIA-AA Guidelines.
  5. MMSE score between the range of 21 to 27.
  6. CDR score of 0.5 or 1.0.
  7. A score on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised within the following education-adjusted ranges:

    • Less than or equal to 11 for 16 or more years of education
    • Less than or equal to 9 for 8-15 years of education
    • Less than or equal to 6 for 0-7 years of education
  8. To qualify for entry, subjects will have CSF Aβ42 levels that are consistent with Alzheimer's disease as measured via mass spectrometry by C2N.
  9. General cognition and functional performance sufficiently preserved that the subject can provide written informed consent.
  10. A minimum of 6 years of education or good work history.
  11. Study partner is available who has frequent contact with the subject (e.g. average of 10 hours per week or more), and can accompany the subject to most visits to answer questions about the subject. Study partner (or other individual) should also oversee study drug administration if needed to ensure compliance with dose regimen.
  12. No evidence of current suicidal ideation or previous suicide attempt in the past month as evaluated in the Columbia Suicide Severity Rating Scale.
  13. MRI scan within the 12 months prior to screening without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease. Lacunes that are not believed to contribute to the subject's cognitive impairment are permissible. If there is no MRI available within a 12-month timeframe, then an MRI must be performed as part of the screening procedures for eligibility.
  14. Stability of permitted medications for 4 weeks prior to baseline. NOTE: Cholinesterase inhibitors and or memantine are allowable only if stable for 12 weeks prior to screen. If taking Aricept (donepezil), no more than 10 mg/day is permitted during the course of the study.
  15. Adequate visual and hearing ability (physical ability to perform all the study assessments).
  16. Good general health with no disease expected to interfere with the study. Subjects may have common age-related disorders (i.e., hypertension, type II diabetes, dyslipidemia, and hypothyroidism) as long as these disorders are being controlled by diet or medication.
  17. Must speak English fluently.

Exclusion Criteria:

  1. Has a history of a psychiatric disorder such as schizophrenia, bipolar disorder or major depression according to the criteria of the most current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Mild depression or history of depression that is stable on treatment with a tricyclic antidepressant SSRI or SNRI medication at a stable dose is acceptable.
  2. Other neurodegenerative diseases, including Parkinson's disease and Huntington's disease, or cerebral tumor.
  3. Dementia other than AD, such as Acquired Immunodeficiency Syndrome (AIDS), Creutzfeldt-Jakob disease (CJD), Lewy Bodies dementia (LBD), Cerebrovascular dementia (CVD), Progressive Supranuclear Palsy (PSP), or normal pressure hydrocephalus (NPH).
  4. History of a seizure disorder.
  5. Clinically significant abnormalities in screening laboratory or ECG results.
  6. Has current serious or unstable illness including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions that, in the investigator's opinion, makes them ineligible for participation in this study.
  7. Has four or more microinfarcts as noted in the MRI scan.
  8. Has cancer or has had a malignant tumor within the past 3 years, except patients who underwent potentially curative therapy with no evidence of recurrence. (Patients with stable untreated prostate cancer or skin cancers are not excluded).
  9. According to the criteria of the most current version of the DSM, alcohol abuse, alcohol dependence, or drug abuse in the past 5 years.
  10. Participation in another clinical trial with an investigational agent and have taken at least one dose of study medication, unless unblinded on placebo, within 16 weeks prior to screening. (The end of a previous investigational trial is the date the last dose of an investigational agent was taken).
  11. Resides in a skilled nursing facility.
  12. Subjects with infection or inflammation of the skin or skin disease at or in proximity to the lumbar puncture site.
  13. History of lumbar spine surgery or chronic low back pain (CLBP).
  14. Subjects whom the site PI deems to be otherwise ineligible.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02925650


Locations
United States, California
UCSD Alzheimer's Disease Research Center Recruiting
La Jolla, California, United States, 92037
Contact: Daniel Szpak, RN    858-249-0558    dszpak@ucsd.edu   
United States, Indiana
IU Health Partners, Adult Neurology Clinic Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Stephanie Fritz, RN, BSN    317-274-4363    safritz@iu.edu   
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Jackie Darrow    410-550-8708    jdarrow2@jhmi.edu   
United States, Missouri
Washington University Sleep Medicine Center Recruiting
Brentwood, Missouri, United States, 63144
Contact: Jill Boyd    314-747-3477    massenaj@wustl.edu   
Sponsors and Collaborators
QR Pharma Inc.
Alzheimer's Disease Cooperative Study (ADCS)

Responsible Party: QR Pharma Inc.
ClinicalTrials.gov Identifier: NCT02925650     History of Changes
Other Study ID Numbers: QR15001
ADC-042-DISC ( Other Identifier: Alzheimer's Disease Cooperative Study (ADCS) )
First Posted: October 6, 2016    Key Record Dates
Last Update Posted: October 15, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data from this research will be shared with other researchers pursuant to the 02/26/2003 "NIH Final Statement on Sharing Research Data".

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by QR Pharma Inc.:
Alzheimer's Disease
SILK™
Pharmacodynamics
Safety
Pharmacokinetics

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Physostigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Miotics
Autonomic Agents
Peripheral Nervous System Agents