10 mg Donepezil Hydrochloride Orally Disintegrating Tablets Under Fasting Conditions.

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01260922
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Days): 30
• Patients Per Site Per Month: 26.4

Study Details

Study Description

Brief Summary

This study investigated the relative bioavailability (rate and extent of absorption) of Donepezil Hydrochloride Orally Disintegrating Tablets, 10 mg by Teva Pharmaceuticals, USA with that of Aricept® Orally Disintegrating Tablets, Manufactured and Marketed by Eisai Inc., following a single oral dose (1 x 10 mg orally disintegrating tablet) in healthy adult subjects administered under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Donepezil Hydrochloride; Drug: Aricept®	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single
• Official Title: A Relative Bioavailability Study of 10 mg Donepezil Hydrochloride Orally Disintegrating Tablets Under Fasting Conditions.
• Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: May 1, 2006
• Actual Study Completion Date: May 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Investigational Test Product Donepezil Hydrochloride 10 mg Orally Disintegrating Tablets	Drug: Donepezil Hydrochloride; 10 mg Orally Disintegrating Tablet
Active Comparator: Reference Listed Drug Aricept® 10 mg Orally Disintegrating Tablets	Drug: Aricept®; 10 mg Orally Disintegrating Tablet; Other Names: Donepezil Hydrochloride (generic name)

Outcome Measures

Primary Outcome Measures

1. Cmax of Donepezil. [Blood samples collected over a 72 hour period.]

   Bioequivalence based on Donepezil Cmax (maximum observed concentration of drug substance in plasma).

2. AUC0-t of Donepezil. [Blood samples collected over a 72 hour period.]

   Bioequivalence based on Donepezil AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Screening Demographics: All volunteers for this study will be healthy men and women 18 years of age or older at the time of dosing. The weight range will not exceed + 20% for height and body frame as per Desirable Weights for Adults-1983 Metropolitan Height and Weight Table.

• Screening Procedures: Each volunteer will complete the screening process within 28 days prior to Period I dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures.

• If female and:

• of childbearing potential, is practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s); or

• is postmenopausal for at least 1 year; or

• is surgically sterile.

Exclusion Criteria:

• Volunteers with a recent history of drug or alcohol addiction or abuse.

• Volunteers with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators).

• Volunteers whose clinical laboratory test values are outside the accepted reference range and when confirmed on reexamination are deemed to be clinically significant.

• Volunteers demonstrating a reactive screen for hepatitis B surface antigen, hepatitis C antibody, or HIV antibody.

• Volunteers demonstrating a positive drug abuse screen when screened for this study.

• Female volunteers demonstrating a positive pregnancy screen.

• Female volunteers who are currently breastfeeding.

• Volunteers with a history of allergic response(s) to donepezil or related drugs.

• Volunteers with a history of clinically significant allergies including drug allergies.

• Volunteers with a clinically significant illness during the 4 weeks prior to Period I dosing (as determined by the clinical investigators).

• Volunteers who currently use tobacco products.

• Volunteers who have taken any drug known to induce or inhibit hepatic drug metabolism in the 28 days prior to Period I dosing.

• Volunteers who report donating greater than 150 mL of blood within the 28 days prior to Period I dosing.

• Volunteers who have donated plasma within 14 days prior to Period I dosing.

• Volunteers who report receiving any investigational drug within 28 days prior to Period I dosing.

• Volunteers who report taking any systemic prescription medication in the 14 days prior to Period I dosing.

• Female volunteers who report the use of oral contraceptives or injectable contraceptives.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRACS Institute, Ltd.	East Grand Forks	Minnesota	United States	56721

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: James D Carlson, Pharm.D., PRACS Institute, Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01260922
• Other Study ID Numbers: R05-1254
• First Posted: Dec 15, 2010
• Last Update Posted: Feb 21, 2011
• Last Verified: Jan 1, 2011

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

Study Results

Participant Flow

Arm/Group Title	Donepezil Hydrochloride (Test) First	Aricept® (Reference) First
Arm/Group Description	10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in first period followed by 10 mg Aricept® Orally Disintegrating Tablets reference product dosed in the second period.	10 mg Aricept® Orally Disintegrating Tablets reference product dosed in first period followed by 10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	13	13
COMPLETED	13	12
NOT COMPLETED	0	1
Period Title: First Intervention
STARTED	13	12
COMPLETED	9	10
NOT COMPLETED	4	2
Period Title: First Intervention
STARTED	9	10
COMPLETED	9	8
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Donepezil Hydrochloride (Test) First	Aricept® (Reference) First	Total
Arm/Group Description	10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in first period followed by 10 mg Aricept® Orally Disintegrating Tablets reference product dosed in the second period.	10 mg Aricept® Orally Disintegrating Tablets reference product dosed in first period followed by 10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	13	13	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	13 100%	26 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	7 53.8%	9 69.2%	16 61.5%
Male	6 46.2%	4 30.8%	10 38.5%
Race/Ethnicity, Customized (participants) [Number]
Hispanic	1 7.7%	0 0%	1 3.8%
Caucasian	12 92.3%	13 100%	25 96.2%
Region of Enrollment (participants) [Number]
United States	13 100%	13 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Cmax of Donepezil.
Description	Bioequivalence based on Donepezil Cmax (maximum observed concentration of drug substance in plasma).
Time Frame	Blood samples collected over a 72 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Donepezil Hydrochloride (Test)	Aricept® (Reference)
Arm/Group Description	10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in either period.	10 mg Aricept® Orally Disintegrating Tablets reference product dosed in either period.
Measure Participants	17	17
Mean (Standard Deviation) [ng/mL]	17800.27 (4515.36)	17280.23 (4032.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil Hydrochloride (Test), Aricept® (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
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	102.16
	Confidence Interval	(2-Sided) 90%; 97.07 to 107.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.

2. Primary Outcome

Title	AUC0-t of Donepezil.
Description	Bioequivalence based on Donepezil AUC0-t (area under the concentration-time curve from time zero to time of last measurable concentration).
Time Frame	Blood samples collected over a 72 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Donepezil Hydrochloride (Test)	Aricept® (Reference)
Arm/Group Description	10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in either period.	10 mg Aricept® Orally Disintegrating Tablets reference product dosed in either period.
Measure Participants	17	17
Mean (Standard Deviation) [ng*h/mL]	466307.49 (85094.55)	490716.21 (86199.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil Hydrochloride (Test), Aricept® (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	ANOVA is to be used to identify the source contributions by factors including subjects, period, formulation and potential interactions. The geometric mean ratio together with the ANOVA residual mean error term are used to identify the statistical basis for the 90% confidence interval for the ratio of the population means (Test [T]/Reference[R]) of the identified metrics (e.g. AUC, Cmax).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	94.75
	Confidence Interval	(2-Sided) 90%; 92.11 to 97.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established if the 90% confidence interval for the ln-transformed geometric mean between the reference (R) and test (T) product fall within the interval of 80-125%.

Adverse Events

Time Frame	Adverse event data was collected over the course of the study, which was approximately 8 weeks in duration.
Adverse Event Reporting Description	Volunteers were monitored throughout the study for any adverse experiences. AEs were collected through both solicited and unsolicited methods. The volunteers were encouraged to report signs, symptoms, and any changes in health to the clinic staff.
Arm/Group Title	Donepezil Hydrochloride (Test) First		Aricept® (Reference) First
Arm/Group Description	10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in first period followed by 10 mg Aricept® Orally Disintegrating Tablets reference product dosed in the second period.		10 mg Aricept® Orally Disintegrating Tablets reference product dosed in first period followed by 10 mg Donepezil Hydrochloride Orally Disintegrating Tablets test product dosed in the second period.
All Cause Mortality
	Donepezil Hydrochloride (Test) First		Aricept® (Reference) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Donepezil Hydrochloride (Test) First		Aricept® (Reference) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Donepezil Hydrochloride (Test) First		Aricept® (Reference) First
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/26 (38.5%)		6/26 (23.1%)
General disorders
Headache	3/26 (11.5%)	3	1/26 (3.8%)	1
Nausea	5/26 (19.2%)	5	4/26 (15.4%)	5
Vomiting	5/26 (19.2%)	13	3/26 (11.5%)	4
Dizziness	0/26 (0%)	0	2/26 (7.7%)	2
Abnormal Dreams	2/26 (7.7%)	2	0/26 (0%)	0
Feeling Hot	2/26 (7.7%)	2	0/26 (0%)	0

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.