Cefdinir for Oral Suspension 250 mg/5mL, Non-fasting

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00835549
• Collaborator: (none)
• Enrollment: 32
• Locations: 2
• Arms: 2
• Patients Per Site: 16

Study Details

Study Description

Brief Summary

The objective of this study is to compare the relative bioavailability of cefdinir for oral suspension 250 mg/5mL (manufactured and distributed by TEVA Pharmaceuticals USA) with that of OMNICEF® for oral suspension, 250 mg/5mL (Abbott) in healthy, adult, non-smoking subjects under non-fasting conditions.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Cefdinir for oral suspension 250 mg/5mL; Drug: OMNICEF® for oral suspension 250 mg/5mL	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability Study of Cefdinir for Oral Suspension 250 mg/5mL Under Non-Fasting Conditions
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Mar 1, 2005
• Actual Study Completion Date: Mar 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Cefdinir for oral suspension 250 mg/5mL; 1 x 250 mg/5mL, single-dose non-fasting
Active Comparator: 2	Drug: OMNICEF® for oral suspension 250 mg/5mL; 1 x 250 mg/5mL, single-dose non-fasting

Outcome Measures

Primary Outcome Measures

1. Cmax (Maximum Observed Concentration) [Blood samples collected over a 14 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 14 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 14 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 non-smokers at least 18 years of age. Subjects will have a BMI (body mass index) between 19 kg/m² and 30 kg/m² (inclusive).

• Each subject will 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 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, SGPT, bilirubin, and alkaline phosphatase.

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

• HIV Screen

• Hepatitis-B, C Screen

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

Subjects will be selected if all above are normal. 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 reference 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 (including penicillin, any penicillin derivative, or any cephalosporin product) should be excluded from the study.

• All subjects will have urine/saliva samples assayed for the presence of drugs of abuse as part of the clinical laboratory screening procedures and at each study period check-in. Subjects found to have urin/saliva 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.

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

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

Subjects who have difficulty fasting or consuming the standard meals will not be allowed to participate.

• Subjects who have had a clinically significant illness within 4 weeks prior to the first dosing of the study will not be allowed to participate.

Subjects who have used a known hepatic enzyme inducer or inhibitor within 30 days prior to the first dosing of the study 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: Soran Hong, M.D., Novum Pharmaceutical Research Services

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00835549
• Other Study ID Numbers: B056502
• 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: Cefdinir

Study Results

Participant Flow

Arm/Group Title	Cefdinir (Test) First	Omnicef® (Reference) First
Arm/Group Description	250mg/5mL Cefdinir for Oral Suspension test product dosed in first period followed by 250mg/5mL Omnicef® for Oral Suspension reference product dosed in the second period.	250mg/5mL Omnicef® for Oral Suspension reference product dosed in first period followed by 250mg/5mL Cefdinir for Oral Suspension test product dosed in the second period.
Period Title: First Intervention
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0
Period Title: First Intervention
STARTED	16	16
COMPLETED	14	16
NOT COMPLETED	2	0
Period Title: First Intervention
STARTED	14	16
COMPLETED	14	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cefdinir (Test) First	Omnicef® (Reference) First	Total
Arm/Group Description	250mg/5mL Cefdinir for Oral Suspension test product dosed in first period followed by 250mg/5mL Omnicef® for Oral Suspension reference product dosed in the second period.	250mg/5mL Omnicef® for Oral Suspension reference product dosed in first period followed by 250mg/5mL Cefdinir for Oral Suspension test product dosed in the second period.	Total of all reporting groups
Overall Participants	16	16	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	16 100%	32 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	5 31.3%	7 43.8%	12 37.5%
Male	11 68.8%	9 56.3%	20 62.5%
Race/Ethnicity, Customized (participants) [Number]
Black	11 68.8%	10 62.5%	21 65.6%
White	5 31.3%	6 37.5%	11 34.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 18.8%	6 37.5%	9 28.1%
Not Hispanic or Latino	13 81.3%	10 62.5%	23 71.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%	16 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Cmax (Maximum Observed Concentration)
Description	Bioequivalence based on Cmax.
Time Frame	Blood samples collected over a 14 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Cefdinir (Test)	Omnicef® (Reference)
Arm/Group Description	250mg/5mL Cefdinir for Oral Suspension test product dosed in either period.	250mg/5mL Omnicef® for Oral Suspension reference product dosed in either period.
Measure Participants	30	30
Mean (Standard Deviation) [ng/mL]	1477.573 (573.068)	1484.677 (531.404)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cefdinir (Test), Omnicef® (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	98.6
	Confidence Interval	() 90%; 94.8 to 102
	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 14 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Cefdinir (Test)	Omnicef® (Reference)
Arm/Group Description	250mg/5mL Cefdinir for Oral Suspension test product dosed in either period.	250mg/5mL Omnicef® for Oral Suspension reference product dosed in either period.
Measure Participants	30	30
Mean (Standard Deviation) [ng*h/mL]	8009.082 (3066.97)	7851.736 (2911.323)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cefdinir (Test), Omnicef® (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	102
	Confidence Interval	() 90%; 98.5 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 14 hour period.

Outcome Measure Data

Analysis Population Description

All participants that completed the study had their samples analyzed.

Arm/Group Title	Cefdinir (Test)	Omnicef® (Reference)
Arm/Group Description	250mg/5mL Cefdinir for Oral Suspension test product dosed in either period.	250mg/5mL Omnicef® for Oral Suspension reference product dosed in either period.
Measure Participants	30	30
Mean (Standard Deviation) [ng*h/mL]	8103.237 (3123.887)	7933.332 (2957.041)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cefdinir (Test), Omnicef® (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	102
	Confidence Interval	() 90%; 98.7 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%.

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.