Using PET Scans to Study Brain Receptor Occupancy of BIIB014 in Healthy Male Volunteers

An Open-Label, Positron Emission Tomography Study to Assess Adenosine A2A Brain Receptor Occupancy of BIIB014 at Multiple Dose Levels in Healthy Male Volunteers

To establish the extent to which BIIB014, following 8 to 12 consecutive days of dosing at selected dose levels, occupies the brain's A2A receptors. Receptor occupancy will be assessed by PET scanning using a radiolabelled tracer.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BIIB014; Other: [11C]SCH442416

Detailed Description

Subjects will be enrolled sequentially into cohorts of 2 to 4 subjects. PET scan results will determine the actual number of cohorts enrolled and the BIIB014 dose given to each subject. Since all enrolled subjects will be receiving BIIB014, this study is being listed as a 1-arm, Single Group study (actual study design is dose escalation).

Participating subjects will be required to reside in the clinical unit for 10 to 14 consecutive days. Participants will receive 1 oral dose of BIIB014 daily for 8 to 12 consecutive days. During the study, subjects will undergo 2 PET scans and 1 MRI. Frequent blood sample for pharmacokinetic assessments will also be performed.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• BMI between 18.0 and 29.0 kg/m2
• Willing to abstain from caffeine-containing products from 1 week prior to dosing until discharge from unit.
• Willing and able to practice effective contraception until 2 months following last dose of study drug.

Exclusion Criteria:

• History of severe allergic reactions or clinically significant allergies.
• History of malignancy, excluding adequately treated basal cell carcinoma.
• History of any clinically significant disease.
• History of claustrophobia or any condition incompatible with MRI/PET scanning.
• History of any exposure to ionizing radiation, with the exception of dental x-rays, within the 12 months prior to dosing.
• Serious infection within the 4 weeks prior to dosing.
• HbA1c > 6%, positive for Hepatitis C or Hepatitis B, presence of HIV or known exposure to HIV, positive G6PD assay, or any other clinically significant abnormal laboratory parameters at Screening.
• Abnormal supine or standing blood pressure or orthostatic hypotension.
• Any prior treatment with antipsychotic medications, dopamine antagonists, or dopaminergic agonists.
• Treatment with any other investigational drug within 3 months prior to dosing.
• Treatment with any prescription medications within 4 weeks prior to dosing.
• History of drug or alcohol abuse within 1 year prior to dosing.
• Current smoker or any tobacco use within 3 months prior to dosing.
• Heavy caffeine consumption within 4 weeks prior to dosing.

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

Other: 1; Various protocol-specified doses of BIIB014 will be used (doses to be determined by PET scan results)

Drug: BIIB014; oral administration of BIIB014, given once daily for 8 to 12 consecutive days, at various doses as specified in protocol; Other: [11C]SCH442416; 11C]SCH442416 is a radiolabelled tracer molecule that specifically binds to adenosine A2A sites and will be used to evaluate receptor occupancy. The target activity will be 370 MBq. [11C]SCH442416 will be administered IV as a bolus injection over 30 seconds following the start of each PET scan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PET scanning with [11C]SCH442416 of the putamen, caudate, nucleus accumbens, thalamus, and cerebellum.	pre-dose and 24h following last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentrations of BIIB014 and its N-acetyl metabolite will be measured in blood plasma	up to 24h following last dose

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Biogen Idec, Cambridge, MA USA

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: September 17, 2007
• First Submitted That Met QC Criteria: September 17, 2007
• First Posted (Estimate): September 18, 2007

Study Record Updates

• Last Update Posted (Estimate): July 30, 2008
• Last Update Submitted That Met QC Criteria: July 29, 2008
• Last Verified: July 1, 2008

More Information

Terms related to this study

• Keywords: Healthy male volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Purinergic Antagonists; Purinergic Agents; Purinergic P1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; 3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-(1,2,3)triazolo(4,5-d)pyrimidine-5-amine; SCH 442416
• Other Study ID Numbers: 204HV101; EUDRACT 2007-001575-10