FASTMAS (Fast-Fail Trials in Mood and Anxiety Spectrum Disorders) Kappa Opioid Receptor Phase 1 Study — KOR1  

Anxiety Disorders Clinical Trial

Official title: A Phase 1 Study of Kappa and Mu Opioid Receptor Occupancy Associated With Repeated Dosing of LY24516302

Status Withdrawn

Clinical Trial Summary

The available treatments for patients with mood and anxiety spectrum disorders have significant limitations. This study will contribute significantly to public health by taking steps to address these limitations by aiding in the interpretation of a study that: 1) tests a promising new treatment for mood and anxiety spectrum disorders; 2) evaluates a potential target in the brain which could serve as the basis for development of additional new candidate compounds for the treatment of patients with mood and anxiety spectrum disorders; 3) establishes more expeditious methods for evaluating potential new therapies for patients with mood and anxiety spectrum disorders; and 4) specifically establishes methods for the development of new therapies targeting anhedonia, an important RDoC (Research Domain Criteria) endpoint.

Clinical Trial Description

This study is an open-label study of two weeks of daily dosing of LY2456302 carried out in 10 healthy volunteers. Subjects will have an initial screening visit where they will have the opportunity to sign informed consent. Those who choose to do so will undergo a series of screening tests to determine whether they meet inclusion/exclusion criteria for this study. Those who qualify will return in 1-7 days for a baseline set of assessments which will include: having MRI imaging carried out on the first day (structural MRI, fMRI during the Monetary Incentive Delay Task, and Resting State Connectivity fMRI), and on the second day having an arterial line placed; undergoing a [11C]-Carfentanil (a synthetic, highly specific mu opioid receptor (mu-OR) agonist) PET mu opioid receptor occupancy study; undergoing a LY2879788 ( radioactive biochemical substance (in particular, a ligand) that is used for diagnosis or for research-oriented study of the receptor systems of the body) PET Kappa Occupancy Study with a single blood sample taken prior to the scan, a sample during the scan, and samples taken at 15, 30, 45, 60, 75, 90, and 120 minutes after the scan to determine whole blood radioactivity, plasma radioactivity, and un-metabolized tracer fraction over time which are needed to determine the input function to the kinetic model for analysis of parameter estimation needed to compute receptor occupancy from the PET scan data; completing a SHAPS; and undergoing a PRT. Note that arterial line placement and serial blood samples are only needed for the LY2879788 scans because, unlike for [11C]-Carfentanil, there is no accepted reference region in the brains of humans for this ligand which necessitates the development of a kinetic model for scan parameter estimation. The next day subjects will begin taking LY2456302 10 mg daily at 11 am and return to the research unit 6 days later for a safety assessment visit. Subjects will then return to the research unit 7 days later during which they will undergo interval history and safety assessments, take their medication at 11 am, and then have MRI imaging at 1:30 pm. A blood sample to determine LY2456302 level will be obtained immediately before and after the MRI imaging session so that we can determine the relationship between ventral striatal activation during the task and serum level of LY2456302. They will then return to the research unit the following day where they will take their last dose of study medication at 11 am and at 1:30 pm will undergo a [11C]-Carfentanil PET mu opioid receptor occupancy study. A blood sample to determine LY2456302 level will be obtained immediately before and after the PET imaging session so that we can determine the relationship between receptor occupancy and serum level of study drug. The following day subjects will have an arterial line placed and undergo LY2879788 PET Kappa Occupancy Study at 9:30 am with a single blood sample taken prior to the scan and samples taken at 15, 30, 45, 60, 75, 90, and 120 minutes after the scan to determine whole blood radioactivity, plasma radioactivity, and un-metabolized tracer fraction over time which are needed to determine the input function to the kinetic model for analysis of parameter estimation needed to compute receptor occupancy from the PET scan data. A blood sample to determine LY2456302 level will also be obtained immediately before and after the PET imaging session so that we can compute the relationship between serum level and receptor occupancy. Subjects will then return 6 days later for a safety assessment after which their participation in the study will end. ;

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Related Conditions & MeSH terms

• Anxiety Disorders

• NCT number: NCT02218775
• Study type: Interventional
• Source: Duke University
• Status: Withdrawn
• Phase: Phase 1
• Start date: October 2014
• Completion date: April 2015