A Study of Repeat Dosing of OROS® Methylphenidate Hydrochloride (CONCERTA®) and Immediate Release Methylphenidate Hydrochloride in Healthy Adults
Condition: Healthy
Intervention: OROS-Methylphenidate; Immediate Release Methylphenidate; Placebo
Intervention description: Each dose of OROS MPH will be 72 mg which will be supplied as two 36 mg overencapsulated capsules; Each dose of IR MPH will be 40 mg which will be supplied as two 20 mg overencapsulated capsules; Placebo will be administered during the first part of the day, and again during the second part of the day.
Intervention MeSH terms: Methylphenidate
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: healthy volunteers

Summary:

      This is a double-blind, randomized, placebo-controlled, five-period crossover study to
      examine the likability of a repeated administration of immediate release methylphenidate
      hydrochloride (IR-MPH 40 mg) and OROS®-MPH (CONCERTA® 72 mg) in healthy adults. Hypotheses
      are as follows:

        -  Hypothesis 1: the subjective feelings of detection and likeability will be greater for
           periods of IR-MPH administration than after OROS-MPH administration irregardless of
           sequence;

        -  Hypothesis 2: the greater ratings of feelings of detection and likeability will be
           associated with the periods of most rapid change in plasma d-MPH and not with the
           magnitude of plasma d-MPH concentration (other than the OROS-MPH to IR-MPH condition in
           which they coincide), and

        -  Hypothesis 3: the subjective feelings of dislike will be greatest for the two conditions
           in which IR-MPH is the second condition.
    

Eligibility 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. All male and female subjects must have used a medically acceptable form of birth
             control for at least one month prior to screening and be 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, limited physical examination (neurologic and cardiac) 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
             electrocardiogram (ECG) or any laboratory test must be determined to be not clinically
             significant by an 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 100 pounds at screening

          7. Agree and are available to return to the study center for five full-day (approximately
             18 hours) study visits held five to 30 days apart within a 22-week period, and willing
             to complete all protocol-specified assessments.

          8. Able to read and comprehend English

        Exclusion Criteria:

          1. Marked anxiety, tension, and agitation since the drug may aggravate these symptoms

          2. Known hypersensitivity to methylphenidate or other components of Concerta or Ritalin

          3. Subjects with glaucoma

          4. Motor tics or with a family history or diagnosis of Tourette's syndrome

          5. Treated with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuation
             of treatment with MAOIs

          6. Presence or history of any medically diagnosed, clinically significant Axis I
             psychiatric disorder (including substance use disorders, bipolar disorder, any
             psychotic disorder)

          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. Any clinically significant chronic disease or unstable medical abnormality by history
             or physical examination, including hypertension, hyperthyroidism, a seizure disorder,
             history of myocardial infarction or stroke, or history of cardiac arrhythmia or heart
             murmur (other than uncomplicated mitral valve prolapse)

          9. Clinically significant abnormal baseline laboratory values which include the
             following:

               -  Values > 20% above the upper range of the laboratory standard of a basic
                  metabolic screen and complete blood count

               -  Exclusionary blood pressure > 140 (systolic) and 90 (diastolic).

               -  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

         10. 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

               -  Prescription stimulants

         11. Have taken an SSRI in the 35 days before initiation of the study medication

         12. Currently physically dependent on benzodiazepines, opiates or alcohol as determined by
             clinical evaluation or positive urine drug screen at screening

         13. 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)

         14. Unable to swallow the study medication whole

         15. Have had a significant blood loss (> 500 mL) or donated blood in the 30 days preceding
             dosing

         16. Have a positive urine drug screen at screening

         17. Have taken an investigational medication or product within the past 30 days

         18. 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