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

• ClinicalTrials.gov Identifier: NCT00301639
• Recruitment Status: Completed
• First Posted: March 13, 2006
• Last Update Posted: July 12, 2011
• Sponsor: Massachusetts General Hospital
• Collaborator: McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
• Information provided by: Massachusetts General Hospital

Tracking Information

• First Submitted Date: March 10, 2006
• First Posted Date: March 13, 2006
• Last Update Posted Date: July 12, 2011
• Study Start Date: March 2005
• Actual Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 10, 2006): 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.
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A PET Study Examining Pharmacokinetics and Dopamine Transporter Receptor Occupancy Of Two Long-Acting Formulations of Methylphenidate in Adults
• Official Title: A PET Study Examining Pharmacokinetics and Dopamine Transporter Receptor Occupancy Of Two Long-Acting Formulations of Methylphenidate in Adults
• Brief 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.
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label)
• Condition: Healthy Volunteers

Intervention

• Drug: OROS methylphenidate hydrochloride
• Drug: methylphenidate hydrochloride

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: March 10, 2006): 40
• Original Enrollment: Same as current
• Study Completion Date: December 2005
• Actual Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)

Eligibility 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.).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00301639
• Other Study ID Numbers: 2004-p-002189
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Thomas J. Spencer, MD, Massachusetts General Hospital
• Study Sponsor: Massachusetts General Hospital
• Collaborators: McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.

Investigators

• Principal Investigator: Thomas Spencer, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: July 2011