Ribavirin 200 mg Tablets Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00835146
• Collaborator: (none)
• Enrollment: 28
• Locations: 2
• Arms: 2
• Duration (Days): 30
• Patients Per Site: 14
• Patients Per Site Per Month: 14.2

Study Details

Study Description

Brief Summary

The objective of this study is to compare the relative bioavailability of ribavirin 200 mg tablets (manufactured by TEVA Pharmaceutical Industries, Ltd. and distributed by TEVA Pharmaceuticals USA) with that of COPEGUS™ 200 mg tablets (Roche) in healthy, adult, non-smoking, females (who are unable to become pregnant) under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Ribavirin 200 mg tablets; Drug: COPEGUS™	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of Ribavirin 200 mg Tablets Under Fasting Conditions
• Study Start Date: Sep 1, 2003
• Actual Primary Completion Date: Oct 1, 2003
• Actual Study Completion Date: Oct 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Ribavirin 200 mg tablets; 1 x 200 mg, single-dose fasting
Active Comparator: 2	Drug: COPEGUS™; 1 x 200 mg, single-dose fasting

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration of Drug Substance in Plasma) [Blood samples collected over a 72 hour period.]

   Bioequivalence based on Cmax.

2. AUC0-72 (Area Under the Concentration-time Curve From Time Zero to Time of 72 Hours) [Blood samples collected over a 72 hour period.]

   Bioequivalence based on AUC0-72.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• All subjects selected for this study will be non-smokers, at least 18 years of age, and a female whi is physically unable to become pregnant (postmenopausal for at least 6 months or surgically sterile). Subjects will have a BMI (body mass index) of 30 or less.

• 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 subject will be given a serum pregnancy test as part of the pre-study 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 each check-in)

• Subjects will be selected if all above are normal.

Exclusion Criteria:

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

• Subjects whose clinical laboratory test values are greater than 20% outside the normal range may be retested. 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 dems the result to not be significant.

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

• Subjects who use tobacco in any form will not be eligible to participate in the study. Three months abstinence is required.

• 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 dosing period 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 or who are able (women with child bearing potential) to become pregnant during the study 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.

• Subjects who do not tolerate venipuncture will not be allowed to participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novum Pharmaceutical Research Services	Houston	Texas	United States	77042
2	Bioassay Laboratory, Inc.	Houston	Texas	United States	77099

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: So Ran Hong, M.D., Novum Pharmaceutical Research Services

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00835146
• Other Study ID Numbers: B036552
• First Posted: Feb 3, 2009
• Last Update Posted: Sep 11, 2009
• Last Verified: Sep 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Test (Ribavirin) First	Reference (Copegus®) First
Arm/Group Description	200 mg Ribavirin Tablets test product dosed in first period followed by 200 mg Copegus® Tablets reference product dosed in the second period.	200 mg Copegus® Tablets reference product dosed in first period followed by 200 mg Ribavirin Tablets test product dosed in the second period.
Period Title: First Intervention
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	14	14
COMPLETED	14	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Test (Ribavirin) First	Reference (Copegus®) First	Total
Arm/Group Description	200 mg Ribavirin Tablets test product dosed in first period followed by 200 mg Copegus® Tablets reference product dosed in the second period.	200 mg Copegus® Tablets reference product dosed in first period followed by 200 mg Ribavirin Tablets test product dosed in the second period.	Total of all reporting groups
Overall Participants	14	14	28
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 100%	14 100%	28 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	14 100%	14 100%	28 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Black	5 35.7%	10 71.4%	15 53.6%
White	2 14.3%	1 7.1%	3 10.7%
Hispanic	7 50%	3 21.4%	10 35.7%
Region of Enrollment (participants) [Number]
United States	14 100%	14 100%	28 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Concentration of Drug Substance in Plasma)
Description	Bioequivalence based on Cmax.
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	Test (Ribavirin)	Reference (Copegus®)
Arm/Group Description	200 mg Ribavirin Tablets test product dosed in either period.	200 mg Copegus® Tablets reference product dosed in either period.
Measure Participants	28	28
Mean (Standard Deviation) [ng/mL]	518.357 (217.183)	526.357 (215.994)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Ribavirin), Reference (Copegus®)
	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	97.9
	Confidence Interval	() 90%; 91.8 to 105
	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	AUC0-72 (Area Under the Concentration-time Curve From Time Zero to Time of 72 Hours)
Description	Bioequivalence based on AUC0-72.
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	Test (Ribavirin)	Reference (Copegus®)
Arm/Group Description	200 mg Ribavirin Tablets test product dosed in either period.	200 mg Copegus® Tablets reference product dosed in either period.
Measure Participants	28	28
Mean (Standard Deviation) [ng*h/mL]	5594.145 (1358.537)	5672.088 (1546.054)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Test (Ribavirin), Reference (Copegus®)
	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	99.3
	Confidence Interval	() 90%; 93.3 to 106
	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.