A Double-blind Randomized, Placebo-controlled, Crossover Study of Single Doses of OROS Methylphenidate Hydrochloride (CONCERTA) and Long-acting Methylphenidate Hydrochloride (RITALIN LA) in Healthy Adults

This study has been completed.
Sponsor:
Collaborator:
McNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00302354
First received: March 13, 2006
Last updated: July 11, 2011
Last verified: July 2011
  Purpose

This is a double-blind, placebo-controlled study, three-period crossover study to examine the likeability of a single dose of OROS MPH (CONCERTAÒ 90mg) and a single dose of Long-acting MPH (RITALIN LAÒ 90mg). Hypotheses are as follows:

Hypothesis 1: OROS-MPH (CONCERTAÒ) will be later than SODOS-MPH (RITALIN LAÒ) in its Tmax (time to Cmax).

Hypothesis 2: The subjective feelings of detection and likeability would be greater for SODOS-MPH (RITALIN LAÒ) than for an equivalent total dose of OROS-MPH (CONCERTAÒ).


Condition Intervention Phase
Healthy Volunteers
Drug: OROS methylphenidate HCl
Drug: SODAS methylphenidate HCl
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Official Title: A Double-blind Randomized, Placebo-controlled, Crossover Study of Single Doses of OROS Methylphenidate Hydrochloride (CONCERTA) and Long-acting Methylphenidate Hydrochloride (RITALIN LA) in Healthy Adults

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Objective measures provided by hourly d and l ritalinic acid and methylphenidate levels from pre-dose and hours 1,2,3,4,5,6,7,8,10, and 12.

Estimated Enrollment: 50
Study Start Date: December 2004
Study Completion Date: September 2005
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Detailed Description:

Our recent work has suggested that the potential euphoriant risk associated with MPH may be moderated by the oral delivery system in which a longer delivery system may be safer than the immediate release one. 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 MPH formulation is the spheroidal oral drug absorption system (SODAS). SODAS-MPH consists of capsules with two types of beads in a 1 to 1 ratio. Evaluating whether different long acting formulations of MPH will differ in their rate of onset of MPH action (plasma level) is of high clinical, scientific and public health relevance. Since the rate of delivery of MPH is a key factor previously associated with detection and likeability of MPH.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Males or non-pregnant, non-lactating females. With the exception of women who have been post-menopausal for a minimum of 12 months prior to screening and those who have undergone hysterectomy or bilateral oophorectomy, all female subjects must have a negative urine pregnancy test at both screening and at each admission to the research unit, and have used a medically acceptable form of birth control for at least one month prior to screening and willing to continue use during the study. Medically acceptable forms of birth control include abstinence, hormonal contraceptives, diaphragm with spermicide, condom with spermicide, intrauterine device, or surgical sterilization (including vasectomy of male partner(s).
  2. Eighteen (18) to 45 years of age, inclusive.
  3. Based on medical history, physical examination, and/or lab results, are considered healthy and free of any conditions that may interfere with participation in the study. Any abnormalities at screening on results of ECG or any laboratory test must be determined to be not clinically significant by the investigator.
  4. Agree to not use prescription stimulants (except for the study medication) during the study.
  5. Have venous access sufficient for blood sampling as determined by clinical examination.
  6. Weigh at least 110 pounds at screening.
  7. Agree and are available to return to the study center for three full-day (approximately 14 hours) study visits held five to 30 days apart within a 10-week period, and willing to complete all protocol-specified assessments.
  8. Able to read and comprehend English

Exclusion Criteria:

  1. Known hypersensitivity to methylphenidate or components of CONCERTA or RITALIN, or to the sympathomimetic amines.
  2. Presence or history of any medically diagnosed, clinically significant Axis I psychiatric disorder (including substance use disorders, bipolar disorder, any psychotic disorder, Tourette's disorder or family history of Tourette's)
  3. Any clinically significant chronic disease or unstable medical abnormality by history or physical examination, including hypertension, glaucoma, hyperthyroidism, a seizure disorder, history of myocardial infarction or stroke, or history of cardiac arrhythmia or heart murmur (other than uncomplicated mitral valve prolapse).
  4. Clinically significant abnormal baseline laboratory values which include the following:

    1. Values > 20% above the upper range of the laboratory standard of a basic metabolic screen.
    2. Exclusionary blood pressure > 140 (systolic) and 95 (diastolic).
    3. Exclusionary ECG parameters: QTC > 460 msec, QRS > 120 msec, and PR > 200 msec. Subjects having ECG evidence of ischemia or arrhythmia as reviewed by an independent cardiologist.
  5. Currently taking a monoamine oxidase inhibitor or have taken a monoamine oxidase inhibitor in the 14 days before initiation of study medication.
  6. Currently taking or require any of the following medications: clonidine or other alpha-2 adrenergic receptor agonists, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), theophylline, coumarin anticoagulants, anticonvulsants, or prescription stimulants.
  7. Have taken an SSRI in the 35 days before initiation of the study medication.
  8. Currently physically dependent on benzodiazepines, opiates or alcohol as determined by clinical evaluation or positive urine drug screen at screening.
  9. Preexisting severe gastrointestinal narrowing (pathologic or iatrogenic, for example: small bowel inflammatory disease, "short gut" syndrome due to adhesions or decreased transit time, past history of peritonitis, cystic fibrosis, chronic intestinal pseudoabsorption, or Meckel's diverticulum).
  10. Unable to swallow the study medication whole.
  11. Have had a significant blood loss (>500 mL) or donated blood in the 30 days preceding dosing.
  12. Have a positive urine drug screen at screening.
  13. Have taken an investigational medication or product within the past 30 days.
  14. Have taken prescription medications (with the exception of birth control methods) within seven days of screening or is anticipated to need any medications, over-the- counter products (other than acetaminophen), or herbal supplements during the study.
  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: NCT00302354

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: NCT00302354     History of Changes
Other Study ID Numbers: 2004-P-002212
Study First Received: March 13, 2006
Last Updated: July 11, 2011
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 14, 2014