Study Examining Repeat Dosing of OROS® Methylphenidate (CONCERTA®) and Immediate Release Methylphenidate in Healthy Adults

ROS-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. 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.

We will test all combinations of initial administration and then delayed (repeated) administration of the two formulations: IR-MPH to IR-MPH; IR-MPH to OROS-MPH; OROS-MPH to IR-MPH; and OROS-MPH to OROS-MPH.

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 plasma 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

• Subjects with marked anxiety, tension, and agitation since the drug may aggravate these symptoms
• Subjects with known hypersensitivity to methylphenidate or other components of Concerta or Ritalin
• Subjects with glaucoma
• Subjects with motor tics or with a family history or diagnosis of Tourette's syndrome
• Subjects treated with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation of treatment with MAOIs
• 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)
• Diagnosis of ADHD (attention deficit hyperactivity disorder)
• 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 intelligence quotient (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 (electrocardiogram), 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