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

This study has been completed.
Sponsor:
Collaborator:
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Information provided by (Responsible Party):
Thomas J. Spencer, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00302393
First received: March 10, 2006
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

There are two specific aims of this study. The first is to document the pharmacokinetics of dopamine transporter (DAT) receptor occupancy of repeated administration of orally administered, therapeutic doses of a short immediate release-methylphenidate hydrochloride (IR-MPH) and a long-acting formulation of MPH (OROS-MPH) using positron emission tomography (PET) scanning with C-11 altropane as the ligand. The investigators hypothesize that central nervous system (CNS) DAT occupancy of the OROS-MPH to IR-MPH sequence will be greater than that of IR-MPH to OROS-MPH sequence at 5 hours after the initial administration and that the CNS DAT occupancy of the other two formulations will be intermediate.

The second aim of this study is to assess whether the abuse liability potential of delayed, repeated administrations of different formulations of MPH is moderated by the oral delivery system in which a delivery system with slower onset may be safer than one with more rapid early release.


Condition Intervention Phase
Healthy
Drug: OROS methylphenidate hydrochloride
Drug: methylphenidate hydrochloride
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A PET Study Examining Pharmacokinetics and Dopamine Transporter Receptor Occupancy of Repeat Dosing of OROS® Methylphenidate (CONCERTA®) and Immediate Release Methylphenidate in Healthy Adults

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • The DAT receptor occupancy of OROS MPH and MPH IR using PET scanning with C-11 altropane. Objective measures also provided by d and l ritalinic acid and methylphenidate levels at pre-dose, hour 4, 5 and 6. [ Time Frame: Eligible subjects will be asked to return to the study center for five study visits. ] [ Designated as safety issue: No ]
    The first visit will consist of a baseline PET scan during which no medication will be administered. For the next four study visits, subjects will be administered a first dose of one of the study treatments at hour 0 and then a second dose of one of the study treatments at hour 4. The study visits may be scheduled five to 30 days apart, but each subject must complete the five visits within a ten-week period.


Enrollment: 20
Study Start Date: June 2006
Study Completion Date: February 2008
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IR-MPH
Immediate Release Methylphenidate administered before PET Scan
Drug: methylphenidate hydrochloride
Subjects will be administered a first dose of one of the study treatments at hour 0 and then a second dose of one of the study treatments at hour 4 at each of the four treatment days in a crossover fashion, so that each subject will have received doses of each combination of treatments during the study. Each dose of IR MPH will be 20 mg which will be supplied as one 20 mg capsule. Study treatments will be administered with water following an overnight fast of at least 8 hours.
Active Comparator: Concerta
OROS Methylphenidate (Concerta) administered before PET Scan
Drug: OROS methylphenidate hydrochloride
Subjects will be administered a first dose of one of the study treatments at hour 0 and then a second dose of one of the study treatments at hour 4 at each of the four treatment days in a crossover fashion, so that each subject will have received doses of each combination of treatments during the study. Each dose of OROS MPH will be 36 mg which will be supplied as one 36 mg capsules. Study treatments will be administered with water following an overnight fast of at least 8 hours.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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 plasma 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. Subjects with marked anxiety, tension, and agitation since the drug may aggravate these symptoms
  2. Subjects with known hypersensitivity to methylphenidate or other components of Concerta or Ritalin
  3. Subjects with glaucoma
  4. Subjects with motor tics or with a family history or diagnosis of Tourette's syndrome
  5. Subjects treated with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation of treatment with MAOIs
  6. 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.
  7. 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)
  8. Diagnosis of ADHD (attention deficit hyperactivity disorder)
  9. History of head trauma with loss of consciousness, organic brain disorders, seizures, or neurosurgical intervention
  10. Any clinically significant chronic medical condition, in the judgment of the investigator
  11. Mental impairment as evidenced by an intelligence quotient (I.Q.) < 75
  12. Exposure to dopamine receptor antagonists within the previous three (3) months
  13. Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan
  14. Subjects receiving psychotropic medication
  15. Any clinically significant abnormality in the screening laboratory tests, vital signs, or 12-lead ECG (electrocardiogram), outside of normal limits
  16. Any woman of childbearing potential who is seeking to become pregnant or suspects that she may be pregnant
  17. Subjects with a known recent history (within the past six [6] months) of illicit drug or alcohol dependence
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00302393

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
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, Assistant Director, Pediatric Psychopharmacology Unit, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00302393     History of Changes
Other Study ID Numbers: 2005-p-001811
Study First Received: March 10, 2006
Last Updated: October 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
healthy volunteers

Additional relevant MeSH terms:
Methylphenidate
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014