Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects
Brief summary
The objective of this randomized, single-dose, two-way evaluation is to compare the bioequivalence of a test dexmethylphenidate hydrochloride formulation to an equivalent oral dose of the commercially available dexmethylphenidate hydrochloride (Focalin®, Novartis Pharmaceuticals Corporation) in a test population of 24 adult subjects under fed conditions.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods
Interventions
10 mg Tablet
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Sex: Male and Female; similar proportion of each preferred. 2. Age: At least 18 years. 3. Weight: BMI (Body Mass Index) less than or equal to 30. 4. Qualifying subjects must be in good health and physical condition as determined by medical history, complete physical examination, and laboratory tests, all obtained within four (4) weeks prior to study start. The subjects may not have a history of significant past illness expected to affect the investigation. The normal status of subjects will be confirmed by the following procedures: * Laboratory Tests: Hemoglobin, hematocrit, RBC, WBC, differential count, serum electrolytes (Na, K, Cl), fasting blood glucose, BUN, bilirubin,m creatinine, AST, ALT, LD, alkaline phosphatase and urinalysis. HIV, Hepatitis B, Hepatitis C, breath alcohol test, and drugs of abuse testing will be done for screening purposes only. Urine drugs of abuse testing and breath alcohol testing will be repeated at each check-in. Female subjects will have a serum pregnancy test done at screening and a urine pregnancy test prior to each study period at check-in. Laboratory values which are greater than ±20% of the normal range will not qualify unless specifically accepted (with comment) by the Principal Investigator. Results of HIV, Hepatitis B, Hepatitis C, and drugs of abuse must be negative or non-reactive for the subject to qualify for the study. * Electrocardiogram: A 12-lead electrocardiogram (ECG) will be obtained for all subjects. The original tracings, plus interpretation, will be included in the case report form packet. 5. Subjects must read and sign the Consent Form.
Exclusion criteria
1. Subjects not complying with the above inclusion criteria must be excluded from the study. 2. In addition, any one of the conditions listed below will exclude a subject from the study: * History of treatment for alcoholism, substance abuse, or drug abuse within past 24 months. * History of malignancy, stroke, diabetes, cardiac, renal or liver disease, or other serious illness. * History of GERD (gastroesophageal reflux disease), stricture of the esophagus, achalasia, malabsorption syndrome, colon cancer, or chronic colitis, including Crohn's disease. * History of upper gastrointestinal disorder such as dysphagia, esophagitis, gastritis, ulcers. * History of treatment for asthma within the past five (5) years. * History of marked treatable anxiety, tension, agitation. * History of glaucoma * History of motor tics * Family history or diagnosis of tourettes syndrome * History of treatment with monoamine oxidase inhibitors * History of seizures * Inability to sit upright for a period of at least 30 minutes * Females who are pregnant or lactating * History of hypersensitivity to dexmethylphenidate hydrochloride, methylphenidate or any central nervous system stimulant 3. Conditions upon screening which might contraindicate or require that caution be used in the administration of dexmethylphenidate hydrochloride, including: * Sitting systolic blood pressure below 90 mm Hg, or diastolic pressure below 50 mm Hg. * Heart rate less than 50 beats per minute after a 5-minute rest in a seated position. 4. Inability to read and/or sign the consent form. 5. Treatment with any other investigational drug during the four (4) weeks prior to the initial dosing for this study. 6. Subjects who have donated blood within four (4) weeks prior to the initial dosing for this study. 7. Subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.). Three (3) months abstinence is required.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration) | Blood samples collected over a 16 hour period. | Bioequivalence based on Cmax. |
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 16 hour period. | Bioequivalence based on AUC0-t. |
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 16 hour period. | Bioequivalence based on AUC0-inf. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dexmethylphenidate HCl First 10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in first period followed by 10 mg Focalin® Tablets reference product dosed in the second period. | 12 |
| Focalin® First 10 mg Focalin® Tablets reference product dosed in first period followed by 10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in the second period. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout of 7 Days | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Dexmethylphenidate HCl First | Focalin® First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 12 Participants | 24 Participants |
| Race/Ethnicity, Customized Black | 2 participants | 6 participants | 8 participants |
| Race/Ethnicity, Customized White | 10 participants | 6 participants | 16 participants |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Male | 11 Participants | 7 Participants | 18 Participants |
Outcome results
Primary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on AUC0-inf.
Time frame: Blood samples collected over a 16 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmethylphenidate HCl | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 86046.67 pg*h/mL | Standard Deviation 49869.68 |
| Focalin® | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 84376.75 pg*h/mL | Standard Deviation 43435.19 |
90% CI: [97.09, 104.03]
Primary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Bioequivalence based on AUC0-t.
Time frame: Blood samples collected over a 16 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmethylphenidate HCl | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 81531.55 pg*h/mL | Standard Deviation 40876.96 |
| Focalin® | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 79972.63 pg*h/mL | Standard Deviation 35905.93 |
90% CI: [97.3, 104.29]
Primary
Cmax (Maximum Observed Concentration)
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 16 hour period.
Population: All participants that completed the study had their samples analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dexmethylphenidate HCl | Cmax (Maximum Observed Concentration) | 15668.17 pg/mL | Standard Deviation 5081.48 |
| Focalin® | Cmax (Maximum Observed Concentration) | 14526.09 pg/mL | Standard Deviation 4639.79 |
90% CI: [100.24, 115.98]