Cefadroxil 500 mg Capsules Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834275
• Collaborator: (none)
• Enrollment: 26
• Locations: 2
• Arms: 2
• Duration (Days): 30
• Patients Per Site: 13
• Patients Per Site Per Month: 13.2

Study Details

Study Description

Brief Summary

The objective of this study is to compare the relative bioavailability of cefadroxil 500 mg capsules (manufactured by Teva Pharmaceuticals USA) with that of DURICEF® 500 mg capsules (manufactured by Bristol-Myers Squibb Company) when dosed (1 x 500 mg capsules) in normal healthy non-smoking male and female subjects under fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Cefadroxil 500 mg Capsules; Drug: DURICEF® capsules 500 mg	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Two-Way Crossover, Open-Label, Single-Dose Fasting, Bioequivalence Study of Cefadroxil 500 mg Capsules Versus DURICEF® 500 mg Capsules in Normal Healthy Non-smoking Male and Female Subjects.
• Study Start Date: Sep 1, 2004
• Actual Primary Completion Date: Oct 1, 2004
• Actual Study Completion Date: Oct 1, 2004

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Cefadroxil 500 mg Capsules; 1 x 500 mg
Active Comparator: 2	Drug: DURICEF® capsules 500 mg; 1 x 500 mg

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration) [Blood samples collected over a 12 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 12 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 12 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:

• Non-smoking male or female with a minimum age of 18 years (i.e. non-smoker or non-tobacco user for at least 90 days prior to pre-study medical screening.

• Body mass index (BMI= weight/height2 greater than or equal to 19kg/m2 and less than or equal to 30kg/m2.

• Availability of subject for the entire study period and willingness to adhere to protocol requirements, as evidenced by a signed Informed Consent Form.

• Normal findings in the physical examination, 12-lead ECG and vital signs (blood pressure between 100-140/60-90 mmHg, heart rate between 50-99 beats/min, temperature between 35.8°C and 37.5°C.

• Negative for drugs of abuse nicotine, hepatitis B-surface antigen, hepatitis C and HIV, and for female subjects, pregnancy (serum β-CG).

• No clinical laboratory values outside of the acceptable range as defined by BCR, unless the Principal Investigator decides the are not clinically significant.

• Female subjects who are surgically sterile for at least six months or post-menopausal for at least one year, or who will avoid pregnancy prior to the study, during the study and up until one month after the end of the study.

Exclusion Criteria:

• Known history of hypersensitivity to cefadroxil (e.g. Duricel®) and/or related drugs in the family of cephalosporins (Cephalexin, Cefaclor, Cefazolin, Cefuroxime Axetil, Cefotetan, Cefprozil, Cefixime, Ceftriaxone), and/or penicillins (Amoxicillin, Ampicillin, Clozacillin).

• Known history or presence of fod allergies, or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.

• Any clinically significant illness during the last four weeks prior to entry into this study.

• Presence of andy significant physical or organ abnormality.

• Any subject with a history of drug abuse.

• Any history or evidence of psychiatric or psychological disease (including depression) unless deemed not clinically significant by the Principal Investigator, or medical designate.

• Use of any prescription medication within 14 days preceding entry into this study.

• Use of over-the-counter (OTC) medication within 14 days preceding entry into this study (except for spermicidal/barrier contraceptive products).

• Female subjects: use of contraceptives( oral, transdermal, implant, Mirena® IUD) within 30 days prior to drug administration or a depot injection or progestogen drug (e.g. Depo-Provera®) within one year prior to drug administration.

• Female subjects: presence of pregnancy or lactation.

• Any subject who has had blood drawn within 56 days preceding this study, during the conduct of any clinical study at a facility other than BCR, or within the lockout period specified by a previous study conducted at BCR.

• Participation in a clinical trial with an investigational drug within 30 days preceding this study.

• Any subject who has donated blood within 56 days preceding this study.

• Any subject who has participated as a plasma donor in a plasmapheresis program within seven days preceding this study.

• Significant or recent history of asthma (after 12 years of age).

• Any subject with a recent(less than one year) history of alcohol abuse.

• Known personal history of gastrointestinal illness or disease, particularly colitis.

• Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens).

• Intolerance to venipuncture.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bioassay Laboratory, Inc.	Houston	Texas	United States	77099
2	Biovail Contract Research	Toronto	Ontario	Canada	M1L 4R6

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Paul Y Tam, M.D., Biovail Contract Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00834275
• Other Study ID Numbers: 2920
• 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: Cefadroxil

Study Results

Participant Flow

Arm/Group Title	Cefadroxil (Test) First	Duricef® (Reference) First
Arm/Group Description	500 mg Cefadroxil Capsules test product dosed in first period followed by 500 mg Duricef® Capsules reference product dosed in the second period.	500 mg Duricef® Capsules reference product dosed in first period followed by 500 mg Cefadroxil Capsules test product dosed in the second period.
Period Title: First Intervention
STARTED	13	13
COMPLETED	13	13
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	13	13
COMPLETED	13	13
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	13	13
COMPLETED	13	13
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cefadroxil (Test) First	Duricef® (Reference) First	Total
Arm/Group Description	500 mg Cefadroxil Capsules test product dosed in first period followed by 500 mg Duricef® Capsules reference product dosed in the second period.	500 mg Duricef® Capsules reference product dosed in first period followed by 500 mg Cefadroxil Capsules 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%	12 92.3%	25 96.2%
>=65 years	0 0%	1 7.7%	1 3.8%
Sex: Female, Male (Count of Participants)
Female	8 61.5%	5 38.5%	13 50%
Male	5 38.5%	8 61.5%	13 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 7.7%	1 7.7%	2 7.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 15.4%	5 38.5%	7 26.9%
White	9 69.2%	7 53.8%	16 61.5%
More than one race	1 7.7%	0 0%	1 3.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%	1 7.7%	2 7.7%
Not Hispanic or Latino	12 92.3%	12 92.3%	24 92.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	13 100%	13 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Concentration)
Description	Bioequivalence based on Cmax.
Time Frame	Blood samples collected over a 12 hour period

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Cefadroxil (Test)	Duricef® (Reference)
Arm/Group Description	500 mg Cefadroxil Capsules test product dosed in either period.	500 mg Duricef® Capsules reference product dosed in either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng/mL]	16.595 (3.017)	16.744 (3.316)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cefadroxil (Test), Duricef® (Reference)
	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	99
	Confidence Interval	() 90%; 94 to 104
	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 12 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Cefadroxil (Test)	Duricef® (Reference)
Arm/Group Description	500 mg Cefadroxil Capsules test product dosed in either period.	500 mg Duricef® Capsules reference product dosed in either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng*h/mL]	50.933 (11.546)	50.246 (11.226)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cefadroxil (Test), Duricef® (Reference)
	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	101
	Confidence Interval	() 90%; 98.3 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%

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 12 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Cefadroxil (Test)	Duricef® (Reference)
Arm/Group Description	500 mg Cefadroxil Capsules test product dosed in either period.	500 mg Duricef® Capsules reference product dosed in either period.
Measure Participants	26	26
Mean (Standard Deviation) [ng*h/mL]	52.303 (11.628)	51.770 (11.460)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cefadroxil (Test), Duricef® (Reference)
	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	101
	Confidence Interval	() 90%; 98.3 to 104
	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.

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