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

Sponsor:	Massachusetts General Hospital
Collaborator:	McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00302393

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 III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
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:

Drug Information available for: Dopamine 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 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.

Estimated Enrollment:	20
Study Start Date:	June 2006
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: IR-MPH	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	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.

Arms

Assigned Interventions

Active Comparator: IR-MPH

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

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:

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

Contacts and Locations

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

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:	NCT00302393 History of Changes
Other Study ID Numbers:	2005-p-001811
Study First Received:	March 10, 2006
Last Updated:	July 5, 2011
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 February 09, 2012