A Study to Evaluate the Effect of Bexarotene on Beta-Amyloid and Apolipoprotein E Metabolism in Healthy Subjects

NCT ID: NCT02061878

Last Updated: 2015-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2014-11-30

Brief Summary

The primary objective of this proof of mechanism pilot clinical trial is to determine if the RXR agonist bexarotene acts in humans to alter the CSF levels of apoE and alter the clearance of Amyloid-Beta

Detailed Description

This is a double blinded, investigational drug study designed to measure the effect of bexarotene on the clearance of Aβ total and production of apoE in the human brain of young, healthy individuals with the APOE3/3 genotype. From the date of initial subject recruitment to the issuance of a final study report and closeout activities, the expected total study duration is 6 to 10 months.

Each participant will be screened for eligibility and randomized to receive either oral bexarotene or placebo control ("Test Article").The study has the potential to demonstrate the pharmacodynamic properties of a novel treatment approach to Alzheimer's disease. The primary biomarker measurements obtained from this study are believed to be highly dynamic and able to provide a rapid read-out of the biologic activity of the candidate therapeutic under study. In addition, exploratory analysis will involve a proteomics-based screen to identify proteins within both blood and CSF that are induced by the Test Article, thereby potentially identifying new biomarkers that can be used in future clinical trials to demonstrate bexarotene action and target engagement.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: TRIPLE

Study Groups

Bexarotene

The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days

Group Type: EXPERIMENTAL

Bexarotene

Intervention Type: DRUG

Marketed product Targretin® soft gelatin capsule (75mg/capsule) is over-encapsulated in a size AA-el Swedish orange capsule. The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days.

Placebo

The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days.

Interventions

Bexarotene

Marketed product Targretin® soft gelatin capsule (75mg/capsule) is over-encapsulated in a size AA-el Swedish orange capsule. The subjects will be administered three (3) capsules of Targretin™ (75 mg/capsule) on a twice daily basis (450 mg/day) for five days.

Intervention Type: DRUG

Placebo

The subjects will be administered three (3) capsules of Avicel PH on a twice daily basis (450 mg/day) for five days.

Intervention Type: DRUG

Other Intervention Names

Targretin®; Avicel PH

Eligibility Criteria

Inclusion Criteria

• Young healthy adults (age 21-50)
• APOE3/3 genotype

Exclusion Criteria

• Contraindications for blood or CSF sampling
• Bleeding disorder or taking anticoagulants/antiplatelets
• Chronic active infection
• Blood donation within the past month
• Active drug/alcohol dependence or abuse history with in the last 12 months
• Thyroid dysfunction
• High triglycerides (>3.5 mmol/L)
• High cholesterol (>4.0 mmoL/L)
• Leukopenia, including low neutrophil count (<3 x 10^9/L)
• Neurological or psychiatric disorders
• Homeless or prisoner
• Pregnancy
• Incapable of self-informed consent
• Blood borne disease (HIV, Hepatitis)
• Actively smoking and incapable of using nicotine patches
• Known drug allergy to pain medication or local anesthetic
• Subjects that have participated in another study in the last 30 days
• Abnormalities in lumbar spine previously known within 12 months
• APOE2 or APOE4 allele
• Abnormal EKG

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ReXceptor, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Craig T Curtis, MD

Role: PRINCIPAL_INVESTIGATOR

Compass Research

Locations

Compass Research

Orlando, Florida, United States

Countries

United States

References

Ghosal K, Haag M, Verghese PB, West T, Veenstra T, Braunstein JB, Bateman RJ, Holtzman DM, Landreth GE. A randomized controlled study to evaluate the effect of bexarotene on amyloid-beta and apolipoprotein E metabolism in healthy subjects. Alzheimers Dement (N Y). 2016 Jun 17;2(2):110-120. doi: 10.1016/j.trci.2016.06.001. eCollection 2016 Jun.

Reference Type: DERIVED

PMID: 29067298 (View on PubMed)

Other Identifiers

REXCEPTOR-101

Identifier Type: -

Identifier Source: org_study_id