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

May 26, 2015 updated by: Andrew Krystal

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age 21 through 65 years of age
  • Body mass index 19 through 30 lbs/in2
  • Reliable and willing to be available for the duration of the study
  • Willing and able to give written informed consent to participate
  • Able to understand and comply with instructions
  • If female of childbearing potential, must agree to use dual methods of contraception and be willing and able to continue contraception for 6 weeks after the last dose of study drug. Females using oral contraception must have started using it at least 2 months prior to the Baseline Visit
  • If male of childbearing potential, must have undergone surgical sterilization (such as a vasectomy) or agree to use a condom used with a spermicide during participation in the study and for 1 month afterward

Exclusion Criteria:

  • Any clinically significant abnormality of any of the hematology, clinical, chemistry, or urine drug tests
  • Magnetic resonance imaging contraindications at 3 Tesla (e.g., ferromagnetic implants or shrapnel or other incompatibilities)
  • Any clinically significant abnormality of the 12-lead ECG; QTc (corrected QT) interval recorded on screening or predose greater than 450 msec
  • Any clinically significant history of neurologic disease, cancer, or cardiac, respiratory, metabolic, hepatic, renal, gastrointestinal (except appendectomy), dermatological, venereal, hematological disorder or disease
  • Any clinically significant history of Axis I psychiatric disorder, or history of attempted suicide
  • History of seeking advice from a physician or counselor for abuse or misuse of alcohol, non-medical drugs, medicinal drugs or other substance abuse, for example, solvents
  • Any current or previous recreational use of Class A drugs such as opiates, cocaine, ecstasy, LSD (Lysergic acid diethylamide), and amphetamines (Class B)
  • Positive drugs-of-abuse test result at initial exam or at any time during the study
  • An alcoholic intake greater than 7 units per week or unwillingness to stop alcohol consumption for the duration of the study {1 unit = 8 g ethanol (250 mL of beer, 1 glass wine [100 mL], 1 measure spirits [30 mL])}
  • Use of prescribed medication within 30 days of the first study day, or nonprescription medication including herbal remedies except standard dose vitamin supplements and acetaminophen (up to 4 g/day) within 15 days of the first study drug administration, or any medication that would need to be continued during the study
  • Use of any investigational medication within 3 months prior to the start of this study or scheduled to receive an investigational drug other than LY2456302 during the course of this study
  • Any smoking of cigarettes or use of any nicotine containing products within the last month or at any time during the study
  • History of blood donation in the last 3 months
  • History of severe allergies or multiple adverse drug reactions
  • Known hypersensitivity to LY2456302
  • Any history of a clinically significant gastrointestinal condition
  • Any other condition that in the opinion of the investigator would preclude participation in the study
  • Pregnant or lactating
  • History of peptic ulcer disease or gastritis or positive urea breath test

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LY2456302
LY2456302 dosed orally at 10 mg daily for 2 weeks in healthy volunteers
Drug: LY2456302
Mood and Anxiety Disorders

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Primary: Kappa opioid receptor occupancy determined with LY2879788 PET imaging; Mu opioid receptor occupancy determined with [11C]-Carfentanil PET imaging
Time Frame: Both on Day 1
Baseline readings prior to drug dosing
Both on Day 1
Primary: Kappa opioid receptor occupancy determined with LY2879788 PET imaging; Mu opioid receptor occupancy determined with [11C]-Carfentanil PET imaging
Time Frame: Day 16: Trough LY2879788 PET Kappa Occupancy Study (22.5 hours after dosing)
KOR occupancy using LY2879788 imaging at time of peak blood level of LY2456302 achieved with 2 weeks of daily dosing of 10 mg. LY2456302.
Day 16: Trough LY2879788 PET Kappa Occupancy Study (22.5 hours after dosing)
Peak PET Mu Occupancy
Time Frame: Day 15
Mu occupancy using [11C]-Carfentanil PET imaging at time of peal blood level of LY2456302 achieved with 2 weeks of daily dosing of 10 mg LY2456302
Day 15

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Reward Circuit Engagement Outcome
Time Frame: Day 0
Task related fMRI ventral striatal activation occurring with reward and loss anticipation during the Monetary Incentive Delay Task
Day 0
Reward Circuit Engagement Outcome
Time Frame: Day 14 (time of peak drug level)
Task related fMRI ventral striatal activation occurring with reward and loss anticipation during the Monetary Incentive Delay Task
Day 14 (time of peak drug level)
Clinical Anhedonia Outcome Utilizing the Snaith-Hamilton Pleasure Scale (SHAPS)
Time Frame: Screening (Day -7 to Day -1)
The SHAPS is a well validated 14 item questionnaire used to assess anhedonia (the inability to experience pleasure from activities usually found to be enjoyable). Scores on the SHAPS can range from 14 to 56 with higher scores corresponding to higher levels of anhedonia. The SHAPS is the only anhedonia measure to has been found to significantly improve with the administration of a treatment.
Screening (Day -7 to Day -1)
Clinical Anhedonia Outcome Utilizing the Snaith-Hamilton Pleasure Scale (SHAPS)
Time Frame: Day 1
The SHAPS is a well validated 14 item questionnaire used to assess anhedonia (the inability to experience pleasure from activities usually found to be enjoyable). Scores on the SHAPS can range from 14 to 56 with higher scores corresponding to higher levels of anhedonia. The SHAPS is the only anhedonia measure to has been found to significantly improve with the administration of a treatment.
Day 1
Anhedonia Outcome Utilizing the Snaith-Hamilton Pleasure Scale (SHAPS)
Time Frame: Day 15
The SHAPS is a well validated 14 item questionnaire used to assess anhedonia (the inability to experience pleasure from activities usually found to be enjoyable). Scores on the SHAPS can range from 14 to 56 with higher scores corresponding to higher levels of anhedonia. The SHAPS is the only anhedonia measure to has been found to significantly improve with the administration of a treatment.
Day 15
Behavioral Anhedonia Outcome as measured by the Probabilistic Reward Task (PRT)
Time Frame: Day 1
This outcome measure was designed to objectively assess participants' propensity to modulate behavior as a function of reinforcement history. This task has been validated in multiple independent samples
Day 1
Behavioral Anhedonia Outcome as measured by the Probabilistic Reward Task (PRT)
Time Frame: Day 15
Results will be assessed at this time point as compared to Day 1
Day 15

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Andrew Krystal

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Yale University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andrew D Krystal, MD, MS, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 15, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 15, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 18, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 28, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 26, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pro00052483
  • HHSN271201200006I (Other Identifier: NIMH/NIH)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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