A PET Study Examining Pharmacokinetics and Dopamine Transporter Receptor Occupancy Of Two Long-Acting Formulations of Methylphenidate in Adults
Information source: Massachusetts General Hospital
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy Volunteers
Intervention: OROS methylphenidate hydrochloride (Drug); methylphenidate hydrochloride (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Massachusetts General Hospital Official(s) and/or principal investigator(s):
Thomas Spencer, MD, Principal Investigator, Affiliation: Massachusetts General Hospital
Summary
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.
Clinical Details
Official title: A PET Study Examining Pharmacokinetics and Dopamine Transporter Receptor Occupancy Of Two Long-Acting Formulations of Methylphenidate in Adults
Study design: Randomized, Open Label, Historical Control, Crossover Assignment
Primary outcome: 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.
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
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Signed written informed consent to participate in the study.
2. Age: 18 – 55
3. If female, non-pregnant, non-nursing, using an adequate form of birth control or a
negative serum pregnancy test.
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.
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) (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)
3. Tics or Tourette’s Syndrome.
4. Diagnosis of ADHD
5. History of head trauma with loss of consciousness, organic brain disorders, seizures,
or neurosurgical intervention.
6. Any clinically significant chronic medical condition, in the judgment of the
investigator.
7. Mental impairment as evidenced by an I. Q. <75.
8. Exposure to dopamine receptor antagonists within the previous three (3) months.
9. Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan.
10. Subjects receiving psychotropic medication.
11. Any clinically significant abnormality in the screening laboratory tests, vital signs,
or 12-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.
14. Subjects diagnosed with glaucoma.
15. Subjects at risk for MPH toxicity (e. g. individuals with arrhythmias, coronary artery
disease, etc.).
Locations and Contacts
Massachusetts General Hospital, Cambridge, Massachusetts 02138, United States
Additional Information
Starting date: March 2005
Ending date: December 2005
Last updated: March 10, 2006
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