Famciclovir 500 mg Tablets Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834431
• Collaborator: (none)
• Enrollment: 36
• Locations: 2
• Arms: 2
• Duration (Months): 1
• Patients Per Site: 18
• Patients Per Site Per Month: 17.7

Study Details

Study Description

Brief Summary

The objective of this study is to compare the relative bioavailability of famciclovir 500 mg tablets (Novopharm Limited) with that of FAMVIR® 500 mg tablets (Novartis) in healthy adult subjects under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Famciclovir 500 mg Tablets; Drug: Famvir® 500 mg Tablets	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Single Dose, Comparative Bioavailability Study of Two Formulations of Famciclovir 500 mg Tablets Under Fasting Conditions
• Study Start Date: Aug 1, 2004
• Actual Primary Completion Date: Sep 1, 2004
• Actual Study Completion Date: Sep 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Famciclovir 500 mg Tablets; 1 x 500 mg, single-dose fasting
Active Comparator: 2	Drug: Famvir® 500 mg Tablets; 1 x 500 mg, single-dose fasting

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 (Per Participant) [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:

• All subjects selected for this study will be at least 18 years of age.

• Each subject shall be given a general physical examination within 28 days of initiation of the study. Such examination includes, but is not limited to, blood pressure, general observations, and history.

• Each female subject will be give a serum pregnancy test as part of the pre-screening process.

• Adequate blood and urine samples should be obtained within 28 days before beginning of the first period and at the end of the trial for clinical laboratory measurements.

Clinical laboratory measurements will include the following:

• Hematology: hemoglobin, hematocrit, red blood cell count, platelets, and white blood cell count (with differential).

• Clinical Chemistry: creatinine, BUN, glucose, SGOT/AST, SGPT/ALT, bilirubin, and alkaline phosphatase.

• Urine Analysis: pH, specific gravity, protein, glucose, ketones, bilirubin, occult blood, and cells.

• HIV Screen: pre-study only.

• Hepatitis-B, C Screen: pre-study only.

• Drugs of Abuse Screen: pre-study and at check-in each study period.

Electrocardiograms of all participating subjects will be recorded before initiation of the study and filed with each subject's case report forms.

Exclusion Criteria:

• Subjects with a history of alcoholism or drug addiction (during past 2 years), or serious gastrointestinal, renal, hepatic, or cardiovascular disease, tuberculosis, epilepsy, asthma (during past 5 years), diabetes, psychosis or glaucoma will not be eligible for this study.

• Subjects whose clinical laboratory test values are outside the normal range may be retested at the discretion of the clinical investigator. If the clinical values are outside the range on retesting, the subject will not be eligible to participate in the study unless the clinical investigator deems the result to not be significant.

• Subjects who have a history of allergic responses to the class of drug being tested should be excluded form the study.

• All subjects will have urine samples assayed for the presence of drugs of abuse as part of the clinical laboratory screening procedures and at each check-in. Subjects found to have urine concentrations of any of the tested drugs will not be allowed to participate.

• Subjects should not have donated blood and/or plasma for at least thirty (30) days prior to the first dosing of the study.

• Subjects who have taken any investigational drug within thirty (30) days prior to the first dosing of the study will not be allowed to participate.

• Female subjects who are pregnant, breast-feeding, or who are likely to become pregnant during the study will not be allowed to participate. Female subjects of child bearing potential must either abstain from sexual intercourse or use a reliable barrier method (e.g. condom, IUD) of contraception during the course of the study (first dosing until last blood collection) or they will not be allowed to participate. Subjects who have used implanted or injected hormonal contraceptives anytime during the 6 months prior to study dosing, or used oral hormonal contraceptives within 14 days before dosing will not be allowed to participate.

• All female subjects will be screened for pregnancy at check-in each study period. Subjects with positive or inconclusive results will be withdrawn from the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gateway Medical Research, Inc.	St. Charles	Missouri	United States	63301
2	Ba Research Co.	Toronto	Ontario	Canada	M1P2X4

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: NCT00834431
• Other Study ID Numbers: B044501
• First Posted: Feb 3, 2009
• Last Update Posted: Aug 20, 2009
• Last Verified: Aug 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Famciclovir First	Famvir® First
Arm/Group Description	500 mg Famciclovir Tablets test product dosed in first period followed by 500 mg Famvir® Tablets reference product dosed in the second period.	500 mg Famvir® Tablets reference product dosed in first period followed by 500 mg Famciclovir Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	18	18
COMPLETED	18	17
NOT COMPLETED	0	1
Period Title: First Intervention
STARTED	18	17
COMPLETED	18	16
NOT COMPLETED	0	1
Period Title: First Intervention
STARTED	18	16
COMPLETED	18	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Famciclovir First	Famvir® First	Total
Arm/Group Description	500 mg Famciclovir Tablets test product dosed in first period followed by 500 mg Famvir® Tablets reference product dosed in the second period.	500 mg Famvir® Tablets reference product dosed in first period followed by 500 mg Famciclovir Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	18	18	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 100%	18 100%	36 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	10 55.6%	10 55.6%	20 55.6%
Male	8 44.4%	8 44.4%	16 44.4%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 5.6%	1 5.6%	2 5.6%
Black	4 22.2%	1 5.6%	5 13.9%
White	13 72.2%	16 88.9%	29 80.6%
Region of Enrollment (participants) [Number]
United States	18 100%	18 100%	36 100%

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	Famciclovir	Famvir®
Arm/Group Description	500 mg Famciclovir Tablets test product dosed in either period.	500 mg Famvir® Tablets reference product dosed in either period.
Measure Participants	34	34
Mean (Standard Deviation) [ng/mL]	3265.647 (954.529)	3521.118 (876.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Famciclovir, Famvir®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model 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	92
	Confidence Interval	() 90%; 85.9 to 98.6
	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 (Per Participant)
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	Famciclovir	Famvir®
Arm/Group Description	500 mg Famciclovir Tablets test product dosed in either period.	500 mg Famvir® Tablets reference product dosed in either period.
Measure Participants	34	34
Mean (Standard Deviation) [ng*h/mL]	10022.244 (1604.383)	10200.015 (1703.293)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Famciclovir, Famvir®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model 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	98.6
	Confidence Interval	() 90%; 96.2 to 101
	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	Famciclovir	Famvir®
Arm/Group Description	500 mg Famciclovir Tablets test product dosed in either period.	500 mg Famvir® Tablets reference product dosed in either period.
Measure Participants	34	34
Mean (Standard Deviation) [ng*h/mL]	10135.731 (1604.773)	10305.772 (1702.728)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Famciclovir, Famvir®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The ANOVA model 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	98.7
	Confidence Interval	() 90%; 96.3 to 101
	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.