Study Examining Repeat Dosing of OROS® Methylphenidate (CONCERTA®) and Immediate Release Methylphenidate in Healthy Adults
Condition: Healthy
Study type: Interventional
Phase: Phase 3

Summary: 
      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.
    

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.
    

Intervention name(s): OROS methylphenidate hydrochloride; methylphenidate hydrochloride
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Intervention MeSH terms: Methylphenidate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Keywords: healthy volunteers