Dexmethylphenidate Hydrochloride Tablets Under Non-Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00829673
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Dexmethylphenidate Hydrochloride; Drug: Dexmethylphenidate Hydrochloride	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Randomized, Two-Way, Single-Dose, Open-Label Study to Evaluate the Bioequivalence of a Test Tablet Formulation of Dexmethylphenidate Hydrochloride, (10 mg), Compared to an Equivalent Dose of a Commercially Available Reference Product (Focalin®, Novartis Pharmaceuticals Corporation) in 24 Fed, Healthy, Adult Subjects
• Study Start Date: Jun 1, 2004
• Actual Primary Completion Date: Jun 1, 2004
• Actual Study Completion Date: Jun 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Dexmethylphenidate Hydrochloride; 10 mg Tablet
Active Comparator: 2 Focalin®	Drug: Dexmethylphenidate Hydrochloride; 10 mg Tablet; Other Names: Focalin®

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration) [Blood samples collected over a 16 hour period.]

   Bioequivalence based on Cmax.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

1. 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

1. 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.

1. Inability to read and/or sign the consent form.

2. Treatment with any other investigational drug during the four (4) weeks prior to the initial dosing for this study.

3. Subjects who have donated blood within four (4) weeks prior to the initial dosing for this study.

4. Subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.). Three (3) months abstinence is required.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gateway Medical Research, Inc.	St. Charles	Missouri	United States	63301

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Irwin Plisco, M.D., Cetero Research, San Antonio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00829673
• Other Study ID Numbers: 04163
• First Posted: Jan 27, 2009
• Last Update Posted: Aug 19, 2009
• Last Verified: Aug 1, 2009

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Dexmethylphenidate Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Dexmethylphenidate HCl First	Focalin® First
Arm/Group Description	10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in first period followed by 10 mg Focalin® Tablets reference product dosed in the second period.	10 mg Focalin® Tablets reference product dosed in first period followed by 10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	12	12
COMPLETED	11	12
NOT COMPLETED	1	0
Period Title: First Intervention
STARTED	11	12
COMPLETED	11	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dexmethylphenidate HCl First	Focalin® First	Total
Arm/Group Description	10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in first period followed by 10 mg Focalin® Tablets reference product dosed in the second period.	10 mg Focalin® Tablets reference product dosed in first period followed by 10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	12 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 8.3%	5 41.7%	6 25%
Male	11 91.7%	7 58.3%	18 75%
Race/Ethnicity, Customized (participants) [Number]
Black	2 16.7%	6 50%	8 33.3%
White	10 83.3%	6 50%	16 66.7%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Concentration)
Description	Bioequivalence based on Cmax.
Time Frame	Blood samples collected over a 16 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Dexmethylphenidate HCl	Focalin®
Arm/Group Description	10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in either period.	10 mg Focalin® Tablets reference product dosed in either period.
Measure Participants	23	23
Mean (Standard Deviation) [pg/mL]	15668.17 (5081.48)	14526.09 (4639.79)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexmethylphenidate HCl, Focalin®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model containing factors for sequence of products, subjects within sequence, periods, and products was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	107.82
	Confidence Interval	() 90%; 100.24 to 115.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

2. Primary Outcome

Title	AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Description	Bioequivalence based on AUC0-t.
Time Frame	Blood samples collected over a 16 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Dexmethylphenidate HCl	Focalin®
Arm/Group Description	10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in either period.	10 mg Focalin® Tablets reference product dosed in either period.
Measure Participants	23	23
Mean (Standard Deviation) [pg*h/mL]	81531.55 (40876.96)	79972.63 (35905.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexmethylphenidate HCl, Focalin®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model containing factors for sequence of products, subjects within sequence, periods, and products was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	100.74
	Confidence Interval	() 90%; 97.3 to 104.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

3. Primary Outcome

Title	AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity)
Description	Bioequivalence based on AUC0-inf.
Time Frame	Blood samples collected over a 16 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Dexmethylphenidate HCl	Focalin®
Arm/Group Description	10 mg Dexmethylphenidate Hydrochloride Tablets test product dosed in either period.	10 mg Focalin® Tablets reference product dosed in either period.
Measure Participants	23	23
Mean (Standard Deviation) [pg*h/mL]	86046.67 (49869.68)	84376.75 (43435.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexmethylphenidate HCl, Focalin®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model containing factors for sequence of products, subjects within sequence, periods, and products was utilized in comparing the effects between the test and reference products. Differences were declared statistically significant at the 5% level (p<0.05).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the T/R geometric mean x 100
	Estimated Value	100.5
	Confidence Interval	() 90%; 97.09 to 104.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference and test product fall within the interval of 80-125%.

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Principal Investigator is not permitted to discuss or publish trial results.