Study of the Inhibition of [11C]R-rolipram Binding to Brain Phosphodiesterase - 4 (PDE-4) by HT-0712

A PET Study: Single-dose, Open-label Study of the Inhibition of [11C]R-rolipram Binding to Brain Phosphodiesterase - 4 (PDE-4) by HT-0712

This Positron Emission Tomography (PET) imaging study is designed to explore the relationship between HT-0712 dose level and inhibition of brain phosphodiesterase-4 activity, in order to optimize the dosage regimens utilized in subsequent trials.

Study Overview

• Status: Terminated
• Conditions: Healthy Elderly Volunteers
• Intervention / Treatment: Drug: HT-0712

Detailed Description

The objective of this project is to demonstrate the inhibition of human brain PDE4 by HT-0712, by measuring the inhibition of [11C]R-rolipram binding, a radiotracer which also binds to and inhibits PDE4. Plasma samples will be drawn to determine if there is a relationship between plasma pharmacokinetics of HT-0712 and its pharmacodynamic effect, as determined through the inhibition of [11C]R-rolipram binding in the brain.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Upton, New York, United States, 11973
      • Brookhaven National Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Healthy, elderly, non-smoking men and post-menopausal women
• Ability to give informed consent

Main Exclusion Criteria:

• Current or history of uncontrolled hypertension, major depression, Parkinson's disease, stroke and diabetes.
• Physical or behavioral conditions that may alter brain function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HT-0712	Drug: HT-0712; A range of single oral dose levels will be explored, utilizing 5mg and 25mg strength capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PET measurement of HT-0712 inhibition of [11C]R-rolipram binding	To demonstrate Central Nervous System (CNS) exposure and dose-related inhibition of [11C]R-rolipram binding in brain regions of interest by HT-0712 when compared to baseline [11C]R-rolipram binding in the same individual.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain uptake of [11C]R-rolipram, as determined by PET imaging, associated with both maximal plasma concentration of HT-0712 (Tmax) and overall plasma level exposure (AUC) following administration of different dose levels of HT-0712.	Time-activity curves and plasma AUC will be assessed for [11C]R-rolipram at baseline and at 4-hours post oral administration of HT-0712.	1 day

Collaborators and Investigators

• Sponsor: Dart NeuroScience, LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: September 24, 2010
• First Submitted That Met QC Criteria: October 5, 2010
• First Posted (Estimate): October 6, 2010

Study Record Updates

• Last Update Posted (Estimate): June 1, 2011
• Last Update Submitted That Met QC Criteria: May 27, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Other Study ID Numbers: HT-0712-006; BNL IRB #444 (Other Identifier: Brookhaven National Laboratory)