An Open Label Phase I/II Study of Dopamine Transporter Receptor Occupancy With OROS and Immediate Release Methylphenidate as Measured With C-11 Altropane in Human Subjects

The specific aim of this study is to document the pharmacokinetics of DAT receptor occupancy of OROS and immediate release (IR) MPH using PET scanning with C-11 altropane as the ligand. We hypothesize that the time to maximal receptor occupancy and the degree of receptor occupancy of immediate release (IR) MPH will be shorter and greater (respectively) than with an equipotent dose of OROS MPH.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: OROS methylphenidate hydrochloride; Drug: immediate release methylphenidate hydrochloride

Detailed Description

This protocol seeks to document the pharmacokinetics of DAT receptor occupancy of OROS and immediate release (IR) MPH using PET and C-11 altropane. The main target of MPH in the brain is the dopamine transporter (DAT). We have an exquisitely sensitive methodology to measure DAT occupancy using C-11 Altropane and Positron Emission Tomography (PET). This research will provide novel and unique information toward a better understanding of the mechanism of action of long-acting stimulant formulations to enable new drug development and an estimation of the relative abuse potential of the current formulation.

• Study Type: Interventional
• Enrollment: 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02138
      • Massachusetts General Hospital

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:

1. Signed written informed consent to participate in the study.
2. Age: 18 - 55
3. If female, non-pregnant, non-nursing with a negative serum pregnancy test and using an adequate form of birth control.
4. Supine and standing blood pressure within the range 110/60 to 150/90 mmHg.
5. Heart rate, after resting for 5 minutes, within the range 46-90 beats/min.
6. Subjects who are within 20% of the ideal weight for height as
7. Right handed.

Exclusion Criteria:

1. Diagnosis of any psychotic disorder, bipolar disorder, severe depression, severe anxiety, or Autism. Subjects with mild mood, oppositional, conduct, and anxiety disorders may be permitted to participate if considered appropriate by the investigator.

2. Scores of Baseline Scales:

   Hamilton Depression Scale > 17 (out of a possible 67 on the 21-item scale)[18] Beck Depression Inventory > 19 (out of a possible 63 on the 21-item scale)[19] Hamilton Anxiety Scale > 21 (out of a possible 56 on the 14-item scale) [20]

3. Tics or Tourette's Syndrome.
4. History of head trauma with loss of consciousness, organic brain disorders, seizures, or neurosurgical intervention.
5. Any clinically significant chronic medical condition, in the judgment of the investigator.
6. Mental impairment as evidenced by an I.Q. <75.
7. Exposure to dopamine receptor antagonists within the previous three (3) months.
8. Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan.
9. Subjects receiving psychotropic medication.
10. Any clinically significant abnormality in the screening laboratory tests, vital signs, or 11-lead ECG, outside of normal limits.

12. Any woman of childbearing potential who is seeking to become pregnant or suspects that she may be pregnant.

13. Subjects with a known recent history (within the past six (6) months) of illicit drug or alcohol dependence

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The DAT receptor occupancy of OROS MPH and Metadate CD using PET scanning with C-11 Altropane. Objective measures also provided by d and l ritalinic acid and methylphenidate levels at pre-dose through hour 10.

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): April 1, 2004
• Study Completion (Actual): April 1, 2004

Study Registration Dates

• First Submitted: March 10, 2006
• First Submitted That Met QC Criteria: March 10, 2006
• First Posted (Estimate): March 14, 2006

Study Record Updates

• Last Update Posted (Estimate): July 12, 2011
• Last Update Submitted That Met QC Criteria: July 11, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Methylphenidate
• Other Study ID Numbers: 2003-p-002058