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

NCT00593138 | Completed Phase 1

• 1 other identifier: 2006-p-001610
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Drug Binding to DAT Receptors

Keywords

Focalin XR; Adult; PET scan

Outcome Measures

Primary Outcomes (1)

• DAT occupancy from PET scan results

  each study visit

Study Arms (1)

1

EXPERIMENTAL

Drug: dex-methylphenidate

Interventions

dex-methylphenidate DRUG

The drug is administered as a capsule by mouth. Participants are assigned to receive either 20, 30 or 40 mg doses before each scan visit.

Also known as: Focalin XR

1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Signed written informed consent to participate in the study.
• Age: 18 -45, inclusive
• If female, non-pregnant, non-nursing with a negative serum pregnancy test.
• Female subjects will agree to use an acceptable and effective form of birth control during the course of their study participation.
• Supine and standing blood pressure \< 150/90 mmHg.
• Heart rate, after resting for 5 minutes, within the range 46-90 beats/min.
• Right handed.

You may not qualify if:

• 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.
• 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) \[20\]
• Subjects with motor tics or with a family history or diagnosis of Tourette's Syndrome.
• History of head trauma with loss of consciousness, organic brain disorders, seizures, or neurosurgical intervention.
• Any clinically significant chronic medical condition, in the judgment of the investigator.
• In the judgment of the investigator, has a mental impairment as evidenced by an I.Q. \<75.
• Exposure to dopamine receptor antagonists within the previous three (3) months.
• Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan.
• Subjects receiving psychotropic medication including MAO inhibitors within the past 6 to 12 months.
• Any clinically significant abnormality in the screening laboratory tests, vital signs, or 12 lead ECG, outside of normal limits.
• Any pre-existing structural cardiac abnormalities.
• A history or known family history of long QT syndrome or QTc \>450 ms (males) or \>470 ms (females).

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Spencer TJ, Bonab AA, Dougherty DD, Mirto T, Martin J, Clarke A, Fischman AJ. Understanding the central pharmacokinetics of spheroidal oral drug absorption system (SODAS) dexmethylphenidate: a positron emission tomography study of dopamine transporter receptor occupancy measured with C-11 altropane. J Clin Psychiatry. 2012 Mar;73(3):346-52. doi: 10.4088/JCP.10m06393. Epub 2011 Nov 1.

  PMID: 22154896 DERIVED

MeSH Terms

Interventions

Dexmethylphenidate Hydrochloride

Intervention Hierarchy (Ancestors)

Methylphenidate; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Thomas Spencer, MD

  MGH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief, Clinical and Research Program, Pediatric Psychopharmacology

Study Record Dates

• First Submitted: December 28, 2007
• First Posted: January 14, 2008
• Study Start: December 1, 2006
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2009
• Last Updated: October 22, 2013

Record last verified: 2013-10

Locations

US (1)