A Study of [11C]JNJ-42491293, a Possible PET Ligand for the mGlu2 Receptor, in Healthy Adult Volunteers

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT01359852
First received: May 12, 2011
Last updated: July 21, 2011
Last verified: July 2011
  Purpose

The purpose of this study is to evaluate [11C] JNJ-42491293 as a PET ligand in healthy adult volunteers.


Condition Intervention Phase
Healthy
Drug: [11C] JNJ-42491293
Drug: [11C] JNJ-42491293 + JNJ-40411813
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: An Open-Label Study to Investigate the Dosimetry of the Positron Emission Tomography Ligand for the Metabotropic Glutamate Receptor-2 (mGlu2R), [11C]JNJ-42491293, and Displacement by the mGlu2R Positive Allosteric Modulator JNJ-40411813 in Healthy Male Subjects

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Metabolism (uptake, distribution, and clearance) of [11C] JNJ-42491293 in brain (Part B) [ Time Frame: Up to approximately 8 days ] [ Designated as safety issue: No ]
  • Adverse events (All Parts) [ Time Frame: Up to approximately 8 days (Part A); Up approximately 8 days (Part B); Up to 16 days (Part C); Up to approximately 9 days (Part D) ] [ Designated as safety issue: No ]
  • Biodistribution of [11C] JNJ-42491293 (Part A) [ Time Frame: Up to approximately 8 days ] [ Designated as safety issue: No ]
  • Radiation dosimetry of [11C] JNJ-42491293 (Part A) [ Time Frame: Up to approximately 8 days ] [ Designated as safety issue: No ]
  • Peripheral metabolism of [11C] JNJ-42491293 (Part B) [ Time Frame: Up to approximately 8 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Distribution of [11C] JNJ-42491293 in the brain by pre-treatment with single oral doses of JNJ-40411813 (Part C and Part D) [ Time Frame: Up to approximately 16 days (Part C); Up to approximately 9 days (Part D) ] [ Designated as safety issue: No ]
  • Clearance rate of JNJ-40411813 from the brain (Part D) [ Time Frame: Up to approximately 9 days ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: December 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001

[11C] JNJ-42491293 + JNJ-40411813 Part C:[11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v.bolus injection. Volunteers will be pre-treated with JNJ-40411813 between 1.5 to 3 hours prior to the second and prior to the third PET scan,[11C] JNJ-42491293 + JNJ-40411813 Part D:[11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v. bolus injection.

Volunteers will be treated with a single dose of up to 500 mg JNJ-40411813 prior to the second scan and will have a third scan at least 2 hours later to evaluate the rate of clearance of JNJ-40411813 from the brain,[11C] JNJ-42491293 Part A: [11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v. bolus injection and have a 120 minute PET scan.,[11C] JNJ-42491293 Part B:[11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v. bolus injection have a 90 minute PET scan and have arterial and venous blood sampling.

Drug: [11C] JNJ-42491293
Part B:[11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v. bolus injection, have a 90 minute PET scan and have arterial and venous blood sampling.
Drug: [11C] JNJ-42491293 + JNJ-40411813
Part C:[11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v.bolus injection. Volunteers will be pre-treated with JNJ-40411813 between 1.5 to 3 hours prior to the second and prior to the third PET scan
Drug: [11C] JNJ-42491293 + JNJ-40411813

Part D:[11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v. bolus injection.

Volunteers will be treated with a single dose of up to 500 mg JNJ-40411813 prior to the second scan and will have a third scan at least 2 hours later to evaluate the rate of clearance of JNJ-40411813 from the brain

Drug: [11C] JNJ-42491293
Part A: [11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v. bolus injection and have a 120 minute PET scan.

Detailed Description:

This is an open-label (volunteers will know the identity of assigned treatment) study in healthy adult volunteers and will consist of 4 consecutive parts, A, B, C, and D. Advancement to parts B, C, and D will occur only if the objectives of the preceding parts are met. Healthy adult volunteers will be recruited for each part of the study. This will be the first study in which 42491293 will be given to healthy adult volunteers. Part A will investigate the measurement of radiation (referred to as radiation dosimetry) of 42491293. Part B will measure the regional brain kinetics (activity) and binding properties of 42491293. Part C will assess the dose dependent blocking of 42491293 by 40411813 in brain tissues following single oral doses of 40411813. Part D will assess the 'duration of occupancy' of the metabotropic glutamate receptor-2 (mGluR2) positive allosteric modulator (PAM) site in the brain by 40411813 compared to peripheral clearance. In this study, 42491293 will be radio-labeled and evaluated as a potential positron emission tomography (PET) ligand for use in imaging studies of the brain to detect binding of 40411813, a compound being developed for treating patients with psychiatric conditions such as schizophrenia and anxiety disorders. In Parts A,B,C, and D, [11C] JNJ-42491293 (300 to 370 MBq) will be dosed as an i.v. bolus injection. During Part C and D, JNJ-40411813 (up to 500mg) will be administered orally (by mouth) 1.5 to 3 hours prior to scheduled PET scans.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Body mass index (BMI) between 18 and 30 kg/m2, inclusive (BMI = weight/height2)
  • Nonsmokers (at least 3 months before screening)
  • Healthy on the basis of results from physical examination, vital signs, and 12-lead ECG, clinical laboratory tests performed at screening as determined by the Investigator (study physician)
  • Willing to adhere to the prohibitions and restrictions specified in this protocol
  • Healthy volunteers must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

  • History of or current medical illness that the Investigator considers to be clinically significant
  • History of or current psychiatric or neurological illness including claustrophobia (an abnormal fear of being in narrow or enclosed spaces)
  • Exposed to > 1 mSv of ionizing radiation participating as a volunteer in research studies in the year before the start of this study
  • Any clinically significant Magnetic Resonance Imaging (MRI) abnormalities at screening, as determined by a neuroradiologist, which are relevant for the study (not applicable for part A)
  • Metal implants (pacemakers, joint replacements, etc.) or metal splinters or heavy tattoos, which are relevant for MRI (not applicable for Part A).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01359852

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided

Responsible Party: VICE-PRESIDENT, Johnson & Johnson Pharmaceutical Research and Development, L.L.C.
ClinicalTrials.gov Identifier: NCT01359852     History of Changes
Other Study ID Numbers: CR017848, 42491293EDI1001, 2010-022063-36
Study First Received: May 12, 2011
Last Updated: July 21, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
JNJ-42491293
JNJ-40411813
Metabotropic glutamate subtype 2 receptor (mGlu2R)
Positive allosteric modulator (PAM)
positron emission tomography (PET)

ClinicalTrials.gov processed this record on July 22, 2014