A Double-blind, Randomized, Placebo-controlled, Crossover Study of Repeat Dosing of OROS® Methylphenidate Hydrochloride (CONCERTA®) and Immediate Release Methylphenidate Hydrochloride in Healthy Adults

Fecha de inicio: 1 de enero de 2006

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