A PET Study Examining Pharmacokinetics and Dopamine Transporter Receptor Occupancy Of Two Long-Acting Formulations of Methylphenidate in Adults

This study has been completed.

First Received on March 10, 2006. Last Updated on July 11, 2011 History of Changes

Sponsor:	Massachusetts General Hospital
Collaborator:	McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00301639

Purpose

The specific aim of this study is to document the pharmacokinetics of dopamine transporter DAT receptor occupancy of OROS MPH and Metadate CD using PET scanning with C-11 Altropane as the ligand. We hypothesize that CNS DAT occupancy of OROS MPH will be greater than that of Metadate CD at 10 hours after administration.

Condition	Intervention	Phase
Healthy Volunteers	Drug: OROS methylphenidate hydrochloride Drug: methylphenidate hydrochloride	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Open Label
Official Title:	A PET Study Examining Pharmacokinetics and Dopamine Transporter Receptor Occupancy Of Two Long-Acting Formulations of Methylphenidate in Adults

Resource links provided by NLM:

Drug Information available for: Dopamine Dopamine hydrochloride Methylphenidate Methylphenidate hydrochloride

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

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, hr 9, 10 and 11.

Estimated Enrollment:	40
Study Start Date:	March 2005
Estimated Study Completion Date:	December 2005
Primary Completion Date:	December 2005 (Final data collection date for primary outcome measure)

Detailed Description:

OROS-MPH's pharmacokinetic profile uses an increasing delivery of MPH over the day (ascending pharmacokinetic curve). It was designed to replace IR-MPH TID treatment. Another new long-acting formulation is Metadate CD. Metadate CD consists of capsules with two types of beads. It was designed to replace IR-MPH BID treatment. 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). The time course of decay of the C-11 Altropane permits repeated imaging, thus allowing documentation of the pharmacokinetics of DAT receptor occupancy.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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 > 17 (out of a possible 67 on the 21-item scale) (Hamilton 1960) Beck Depression Inventory > 19 (out of a possible 63 on the 21-item scale) (Beck et al 1961) Hamilton Anxiety Scale > 21 (out of a possible 56 on the 14-item scale) (Hamilton 1959)
Tics or Tourette's Syndrome.
Diagnosis of ADHD
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.
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.
Any clinically significant abnormality in the screening laboratory tests, vital signs, or 12-lead ECG, outside of normal limits.
Any woman of childbearing potential who is seeking to become pregnant or suspects that she may be pregnant.
Subjects with a known recent history (within the past six (6) months) of illicit drug or alcohol dependence.
Subjects diagnosed with glaucoma.
Subjects at risk for MPH toxicity (e.g. individuals with arrhythmias, coronary artery disease, etc.).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00301639

Locations

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

Sponsors and Collaborators

Massachusetts General Hospital

McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Investigators

Principal Investigator:

Thomas Spencer, MD

Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Thomas J. Spencer, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00301639 History of Changes
Other Study ID Numbers:	2004-p-002189
Study First Received:	March 10, 2006
Last Updated:	July 11, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Dopamine
Methylphenidate
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents

Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Central Nervous System Stimulants
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 09, 2012