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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00302367
• Other study ID #: 2003-p-002058
• Status: Completed
• Phase: Phase 4
• First received: March 10, 2006
• Last updated: July 11, 2011
• Start date: January 2004
• Est. completion date: April 2004

Study information

• Verified date: July 2011
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2004
• Est. primary completion date: April 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• OROS methylphenidate hydrochloride

• immediate release methylphenidate hydrochloride

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Cambridge	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.