Healthy
Conditions
Keywords
healthy volunteers
Brief 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.
Detailed description
The main goal 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. To this end, the investigators will compare repeated administration of orally administered, therapeutic doses of a short (IR-MPH) and a long-acting formulation of MPH (OROS-MPH) in the following areas: 1. pharmacokinetic profile of MPH assessing rate of onset of MPH action (indexed through change in plasma level) and 2. abuse liability (indexed through detection and likeability). The investigators 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; OROS-MPH to OROS-MPH, and placebo to placebo.
Interventions
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
DRUGPlacebo
Placebo will be administered during the first part of the day, and again during the second part of the day.
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration of d-Methylphenidate | 4 hours | Objective measure determined from blood samples, measured 4 hours after the dose |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from 2005 to 2007 at Massachusetts General Hospital and were recruited using IRB approved postings through web and email.
Pre-assignment details
Based on a comprehensive screening, subjects who did not meet eligibility criteria for the study were excluded. Others withdrew or were lost to follow-up before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers Healthy volunteers each received IR-MPH, OROS-MPH, and matched placebo (in four separate visits) in a four way crossover design. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible after screening | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Healthy Volunteers |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 28.86 years STANDARD_DEVIATION 6.06 |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Peak Plasma Concentration of d-Methylphenidate
Objective measure determined from blood samples, measured 4 hours after the dose
Time frame: 4 hours
Population: All subjects received each combination of medications on a separate day (total= 5 days)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Placebo | Peak Plasma Concentration of d-Methylphenidate | 0.00 mg/L | Standard Deviation 0 |
| IR-MPH + OROS MPH | Peak Plasma Concentration of d-Methylphenidate | 15.06 mg/L | Standard Deviation 5 |
| IR-MPH +IR-MPH | Peak Plasma Concentration of d-Methylphenidate | 25.34 mg/L | Standard Deviation 7.3 |
| OROS-MPH+OROS-MPH | Peak Plasma Concentration of d-Methylphenidate | 20.34 mg/L | Standard Deviation 6.4 |
| OROS-MPH+ IR-MPH | Peak Plasma Concentration of d-Methylphenidate | 28.79 mg/L | Standard Deviation 8.3 |