Mycophenolate Mofetil 250 mg Capsules Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00911274
• Collaborator: (none)
• Enrollment: 53
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 52

Study Details

Study Description

Brief Summary

The objective of this study was to compare the oral bioavailability of an investigational formulation of mycophenolate mofetil (MMF) 250 mg capsules to an equivalent dose of the commercially available reference product, CellCept® (mycophenolate mofetil) 250 mg administered to healthy subjects following an overnight fast of at least 10 hours.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Mycophenolate Mofetil; Drug: CellCept®	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Single-Dose, 2-Period, 2-Treatment, 2-Way Crossover Bioequivalence Study of Mycophenolate Mofetil 250 mg Capsules Under Fasting Conditions
• Study Start Date: Oct 1, 2006
• Actual Primary Completion Date: Nov 1, 2006
• Actual Study Completion Date: Nov 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test (mycophenolate mofetil) First Mycophenolate Mofetil 250 mg Capsule dosed in first period followed by CellCept® 250 mg Capsule dosed in second period.	Drug: Mycophenolate Mofetil; 250 mg Capsule
Active Comparator: Reference (CellCept®) First CellCept® 250 mg Capsule dosed in first period followed by Mycophenolate Mofetil 250 mg Capsule dosed in second period.	Drug: CellCept®; 250 mg Capsule

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration [Blood samples collected over 72 hour period]

   Bioequivalence based on Cmax

2. AUC0-inf - Area Under Concentration-time Curve From Time Zero to Infinity (Extrapolated) [Blood samples collected over 72 hour period]

   Bioequivalence based on AUC0-inf

3. AUC0-t - Area Under Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration [Blood samples collected over 72 hour period]

   Bioequivalence based on AUC0-t

Eligibility Criteria

Criteria

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

Inclusion Criteria:

All subjects must satisfy the following criteria to be considered for study participation:

• Subject must be male or non-pregnant, non-breast-feeding female

• Subject must be at least 18 years of age

• Subject must have a Body Mass Index (BMI) between 19 and 30 kg/m2, inclusive, and body weight should be at least 50 kg (110 lbs)

• Female Subjects - not surgically sterile or at least two years postmenopausal - must agree to utilize one of the following forms of contraception, if sexually active with a male partner, from screening through completion of the study. Approved forms of contraception are abstinence, double barrier (condom with spermicide, diaphragm with spermicide), intra-uterine device (IUD), or vasectomized partner (6 months minimum since vasectomy).

• Subject must voluntarily consent to participate in this study and provide their written informed consent prior to the start of any study-specific procedures.

• Subject is willing and able to remain in the study unit for the entire duration of each confinement period and return for any outpatient visits.

Exclusion Criteria:

Subjects may be excluded for any of the following:

• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition which, in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results.

• Has a clinically significant abnormal finding on the physical exam, medical history, ECG or clinical laboratory results at screening.

• History or presence of allergic or adverse response to mycophenolate mofetil or related drugs.

• Has been on a significantly abnormal diet during the four weeks preceding the first dose of study medication.

• Has donated blood or plasma within 30 days prior to the first dose of study medication.

• Has participated in another clinical trial within 30 days prior to the first dose of study medication.

• Has used any over-the-counter (OTC) medication, including nutritional supplements, within 7 days prior to the first dose of study medication.

• Has used any prescription medication, including hormonal contraceptive or hormonal replacement therapy, within 14 days prior to the first dose of study medication.

• Has been treated with any known enzyme altering drugs such as barbiturates, phenothiazines, cimetidine, carbamazepine, etc., within 30 days prior to the first dose of study medication.

• Has smoked or used tobacco products within 90 days prior to the first dose of study medication.

• Is a female with a positive pregnancy test result.

• Female who has used implanted hormonal contraceptives anytime during the 6 months prior to study start.

• Has an intolerance to venipuncture.

• Has difficulty fasting or consuming standard meals.

• Has a positive urine screen for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, opiates)

• Has a history of drug or alcohol abuse.

• Has had a positive test for, or has been treated for hepatitis B, hepatitis C or HIV.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedra Clinical Research, LLC	Austin	Texas	United States	78759

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Frederick A Bieberdorf, MD, Cedra Clinical Research, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00911274
• Other Study ID Numbers: 20-982-AU
• First Posted: Jun 1, 2009
• Last Update Posted: Sep 23, 2009
• Last Verified: Aug 1, 2009

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

Study Results

Participant Flow

Arm/Group Title	Mycophenolate Mofetil (Test) First	CellCept® (Reference) First
Arm/Group Description	Mycophenolate Mofetil 250 mg Capsule dosed in first period followed by CellCept® 250 mg Capsule dosed in second period.	CellCept® 250 mg Capsule dosed in first period followed by Mycophenolate Mofetil 250 mg Capsule dosed in second period.
Period Title: Period 1
STARTED	27	26
COMPLETED	27	26
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	27	26
COMPLETED	27	26
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Mycophenolate Mofetil (Test) First	CellCept® (Reference) First	Total
Arm/Group Description	Mycophenolate Mofetil 250 mg Capsule dosed in first period followed by CellCept® 250 mg Capsule dosed in second period.	CellCept® 250 mg Capsule dosed in first period followed by Mycophenolate Mofetil 250 mg Capsule dosed in second period.	Total of all reporting groups
Overall Participants	27	26	53
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	27 100%	26 100%	53 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	8 29.6%	15 57.7%	23 43.4%
Male	19 70.4%	11 42.3%	30 56.6%
Race/Ethnicity, Customized (Number) [Number]
White	21 77.8%	20 76.9%	41 77.4%
Black	3 11.1%	5 19.2%	8 15.1%
Asian	2 7.4%	0 0%	2 3.8%
American Indian	1 3.7%	1 3.8%	2 3.8%
Region of Enrollment (participants) [Number]
United States	27 100%	26 100%	53 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 72 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study was included in the statistical analysis.

Arm/Group Title	Mycophenolate Mofetil (Test)	CellCept® (Reference)
Arm/Group Description	Mycophenolate Mofetil 250 mg Capsule dosed in either period.	CellCept® 250 mg Capsule dosed in either period.
Measure Participants	53	53
Mean (Standard Deviation) [µg/mL]	8.5858 (4.1578)	9.2170 (3.8895)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mycophenolate Mofetil (Test), CellCept® (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	92.41
	Confidence Interval	() 90%; 82.77 to 103.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

2. Primary Outcome

Title	AUC0-inf - Area Under Concentration-time Curve From Time Zero to Infinity (Extrapolated)
Description	Bioequivalence based on AUC0-inf
Time Frame	Blood samples collected over 72 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study was included in the statistical analysis.

Arm/Group Title	Mycophenolate Mofetil (Test)	CellCept® (Reference)
Arm/Group Description	Mycophenolate Mofetil 250 mg Capsule dosed in either period.	CellCept® 250 mg Capsule dosed in either period.
Measure Participants	53	53
Mean (Standard Deviation) [µg*hr/mL]	15.7365 (4.2691)	15.7289 (4.2771)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mycophenolate Mofetil (Test), CellCept® (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	101.30
	Confidence Interval	() 90%; 97.84 to 104.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

3. Primary Outcome

Title	AUC0-t - Area Under Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration
Description	Bioequivalence based on AUC0-t
Time Frame	Blood samples collected over 72 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study was included in the statistical analysis.

Arm/Group Title	Mycophenolate Mofetil (Test)	CellCept® (Reference)
Arm/Group Description	Mycophenolate Mofetil 250 mg Capsule dosed in either period.	CellCept® 250 mg Capsule dosed in either period.
Measure Participants	53	53
Mean (Standard Deviation) [µg*hr/mL]	14.8297 (4.2217)	14.6761 (4.1985)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mycophenolate Mofetil (Test), CellCept® (Reference)
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-t, AUCinf and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	101.00
	Confidence Interval	() 90%; 97.77 to 104.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

PI is not permitted to discuss or publish trial results.