Study of Dopamine Transporter Receptor Occupancy With Long-acting Dex-methylphenidate

• Status: Completed
• Trial end date: 2009-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The objectives of this study are to document the pharmacokinetics of the adequacy of DAT receptor occupancy d-MPH formulation in three doses (20 mg, 30 mg, and 40 mg) using PET scanning with C-11 Altropane as the ligand across a range of times. It has been estimated that MPH is effective when the average CNS DAT occupancy is 50% or greater. Focalin XR has been shown to be clinically effective in an analog classroom as early as 1 hour and as late as 12 hours. Therefore, it is hypothesized that the average DAT occupancy will be adequate (50% or greater) at time periods corresponding to the times of clinical efficacy.

The first objective is to examine the onset of action by testing whether average DAT occupancy will be adequate (50% or greater) at 1 hour after dosing for each dose tested (20 mg, 30 mg, 40 mg).

The second objective is to test the adequacy of average DAT occupancy in a range of later times for each dose. The times chosen (8, 10 and 12 hours) correspond to times Focalin XR has been shown to be clinically effective in an analogue classroom study. A range of times have been chosen since, while effective at 12 hours, the degree of clinical effectiveness decreased with later time periods. The adequacy of DAT occupancy across this range of time periods will provide important details on the in vivo molecular action of the medicine at periods of critical clinical activity.

The third exploratory objective is to examine a time period later then those previously tested with the highest dose. Since the clinical effectiveness of Focalin XR has not been tested out to 14 hours, it is unknown whether it is effective at 14 hours. If Focalin XR were to be effective at 14 hours it would be more likely at the highest dose.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Massachusetts General Hospital
• Treatments: Dexmethylphenidate Hydrochloride; Dopamine; Methylphenidate

Criteria

Inclusion Criteria:

1. Signed written informed consent to participate in the study.

2. Age: 18 -45, inclusive

3. If female, non-pregnant, non-nursing with a negative serum pregnancy test.

4. Female subjects will agree to use an acceptable and effective form of birth control during the course of their study participation.

5. Supine and standing blood pressure < 150/90 mmHg.

6. Heart rate, after resting for 5 minutes, within the range 46-90 beats/min.

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 > 12 (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. Subjects with motor tics or with a family history or diagnosis of 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. In the judgment of the investigator, has a 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 including MAO inhibitors within the past 6 to 12 months.

10. Any clinically significant abnormality in the screening laboratory tests, vital signs, or 12 lead ECG, outside of normal limits.

11. Any pre-existing structural cardiac abnormalities.

12. A history or known family history of long QT syndrome or QTc >450 ms (males) or >470 ms (females).

13. Any family history of cardiac sudden death.

14. QTc prolongation of QTc > 450 ms (male) or 470 ms (female), hypertension or cardiac arrhythmia, or increased heart rate for age in the judgment of the investigator at screening.

15. A history of cardiac structural abnormality

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

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

18. Subjects diagnosed with glaucoma.

19. Subjects at risk for MPH toxicity (e.g. individuals with arrhythmias, coronary artery disease, etc.).