Pomaglumetad Effects on Glutamate Biomarkers

Biomarker Assessment of Pomaglumetad on Glutamate Targets: Proof of Clinical Mechanism of Action (POCM)

The study will evaluate the effects of the mGluR2/3 partial agonist LY2140023 (Pomaglumetad Methionil, "POMA") at selected doses on ketamine-stimulated glutamate release in prefrontal cortex as measured by pharmacoBOLD fMRI (also termed resting BOLD fMRI).

Study Overview

• Status: Completed
• Conditions: Healthy Controls
• Intervention / Treatment: Drug: POMA; Drug: placebo

Detailed Description

This study evaluates the effects of POMA at selected doses on ketamine-stimulated glutamate increase in the prefrontal cortex hypothesized to simulate the synaptic dysregulation that occurs endogenously in the pathogenesis of schizophrenia. The purpose of this is: 1) to determine whether the low dose (40 mg BID) utilized in recent (failed) clinical trials is sufficient to engage the primary target and 2) whether a higher (160 mg BID) dose, representing the maximum tolerated dose of POMA, engages the target to a greater degree. This study will further validate pharmacoBOLD as biomarker of mGluR2/3 target engagement, permitting its future use in other glutamatergic drug development.

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama, Birmingham
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10016
      • New York University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Medically healthy
• Capable of understanding the study procedures and able to provide informed consent
• Men and women must agree to use a reliable method of birth control during the study. Women who are post-menopausal or otherwise not of childbearing potential are also eligible

Exclusion Criteria:

• Current or past Axis I psychiatric history
• Positive urine toxicology
• History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated in prior research ketamine studies will be eligible. Subjects can have infusions not more frequently than biweekly, and not more than 1/month on average, therefore subjects entering the study will need to wait one month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.
• History of first-degree relative with schizophrenia
• History of violence
• Presence or positive history of significant medical illness
• Presence or positive history neurological illness or any other disease/procedure/accident/intervention association with significant injury to or malfunction of the central nervous system (CNS) or history of significant head injury
• Pregnancy or breast feeding
• Metal implants, pacemaker, other metal or paramagnetic objects contained within the body
• Medicinal patch, unless removed prior to MRI scan
• Currently taking any psychotropic medication, including antidepressant medications, benzodiazepines, antipsychotic medications, mood stabilizers, anti-epileptic medications and stimulants.
• Claustrophobia
• Suicidal ideation with intent or plan in the 6 months prior to screening
• Weight > 86.95 kg (191.2 lbs)
• Subthreshold pharmacoBOLD response during screening ketamine infusion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: POMA 40 mg BID; 40 mg BID for 10 days	Drug: POMA; Pomaglumetad ("POMA") is a mGluR 2/3 partial agonist; Other Names: Pomaglumetad
Experimental: POMA 160 mg BID; 160 mg BID for 10 days	Drug: POMA; Pomaglumetad ("POMA") is a mGluR 2/3 partial agonist; Other Names: Pomaglumetad
Placebo Comparator: Placebo; Placebo BID for 10 days	Drug: placebo; matching placebo tablets; Other Names: placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PharmacoBOLD change	pharmacoBOLD change, as summarized by the Amplitude measure	Day 1 to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brief Psychiatric Rating Scale (BPRS)	Clinical rating scale assessing common psychiatric symptoms	Day 1 to Day 10
Clinician Administered Dissociative States Scale (CADSS)	Rates dissociative symptoms	Day 1 to Day 10

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Jeffrey A Lieberman, MD, New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): April 28, 2018
• Study Completion (Actual): May 25, 2018

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 27, 2016
• First Posted (Estimate): September 29, 2016

Study Record Updates

• Last Update Posted (Actual): September 12, 2018
• Last Update Submitted That Met QC Criteria: September 10, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 7285 (CTEP); 271201200007I-4-27100003-2 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Submit to NDCT