Mycophenolate Mofetil Tablets Under Fasting Conditions

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00907907
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Duration (Months): 1
• Patients Per Site Per Month: 39.3

Study Details

Study Description

Brief Summary

The objective of this study was to evaluate the comparative bioavailability between Mycophenolate Mofetil 500 mg Tablets (test) and CellCept® 500 mg tablets (reference), after a single-dose in healthy subjects under fasting conditions.

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

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Official Title: A Single-Dose, Replicate, Comparative Bioavailability Study of Two Formulations of Mycophenolate Mofetil 500 mg Tablets Under Fasting Conditions
• Study Start Date: Jul 1, 2006
• Actual Primary Completion Date: Aug 1, 2006
• Actual Study Completion Date: Aug 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mycophenolate Mofetil (test) First Mycophenolate Mofetil Tablets, 500 mg dosed in first period followed by CellCept® Tablets, 500 mg dosed in second period; sequence repeated in third and fourth periods.	Drug: Mycophenolate Mofetil; Mycophenolate Mofetil Tablet 500 mg
Active Comparator: Cellcept® (reference) First CellCept® Tablets, 500 mg dosed in first period followed by Mycophenolate Mofetil Tablets, 500 mg dosed in second period; sequence repeated in third and fourth periods.	Drug: CellCept® Tablets; CellCept® Tablets, 500 mg

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 the 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 the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) [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:

• Healthy, non-smoking male subjects, 18 years of age or older.

• Healthy, non-smoking post-menopausal or surgically sterile females 18 years of age or older.

• BMI ≥ 19 and ≤ 30.

• Negative for:

1. HIV.

2. Hepatitis B surface antigen and Hepatitis C antibody.

3. Using drugs of abuse test (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone).

4. Urine cotinine test

5. Serum HCG consistent with pregnancy (females only)

• No significant diseases or clinically significant findings in a physical examination.

• No clinically significant abnormal laboratory values.

• No clinically significant findings in vital signs measurements and a 12-lead electrocardiogram (ECG).

• Be informed of the nature of the study and given written consent prior to receiving any study procedure.

• Females who participate in this study must be unable to have children:

1. post-menopausal for at least 1 year - no menstrual cycle for 12 months and LH and FSH levels judged by a physician to be consistent with post-menopausal status.

OR

1. Proof of surgical sterility.

• Females who participate in this study are not pregnant and/or non-lactating.

Exclusion Criteria:

• Known history or presence of any clinically significant medical condition.

• Known or suspected carcinoma.

• Known or suspected increased susceptibility to infection.

• Known history or presence of active tuberculosis (TB).

• Results of a previous TB skin test greater than 5 mm in diameter.

• Lived in or traveled, during the last 8 weeks, to a country defined by the Public Health Agency of Canada as having WHO estimated sputum smear positive pulmonary TB rate of 15 per 100,000 or higher.

• Known history or presence of:

1. Hypersensitivity or idiosyncratic reaction to mycophenolate mofetil and/or any other drug substances with similar activity.

2. Alcoholism within the last 12 months.

3. Drug dependence and/or substance abuse.

4. Use of tobacco or nicotine-containing products within the last 6 months.

• On a special diet within 4 weeks prior to drug administration (e.g. liquid, protein, raw food diet).

• Participated in another clinical trial or received and investigational product within 30 days prior to drug administration.

• Donated up to 250 mL of blood within the previous 30 days OR Donated from 251 to 499 mL of blood in the previous 45 days OR Donated more than 499 mL of blood in the previous 56 days (based on the Canadian Blood Services guideline for blood donation.

• Females taking oral or transdermal hormonal contraceptives within 14 days preceding period 1 dosing.

• Females having taken implanted or injected hormonal contraceptives within 6 months prior to period 1 dosing.

• Requirement of any non-topical medication (prescription and/or over-the-counter) on a routine basis.

• Difficulty fasting or consuming the standard meals.

• Do not tolerate venipuncture.

• Unable to read or sign the ICF.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pharma Medica Research Inc.	Toronto	Ontario	Canada	M1R 5A3

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Xueyu (Eric) Chen, MD, Ph.D., FRCP(C), Pharma Medica Research, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00907907
• Other Study ID Numbers: 2006-1263
• First Posted: May 25, 2009
• Last Update Posted: Aug 20, 2009
• Last Verified: Aug 1, 2009

• Keywords provided by , ,: Bioequivalence; 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 Tablets, 500 mg dosed in first period followed by CellCept® Tablets, 500 mg dosed in second period; sequence repeated in third and fourth periods.	CellCept® Tablets, 500 mg dosed in first period followed by Mycophenolate Mofetil Tablets, 500 mg dosed in second period; sequence repeated in third and fourth periods.
Period Title: Period 1
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	19	18
COMPLETED	19	18
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Mycophenolate Mofetil (Test) First	Cellcept® (Reference) First	Total
Arm/Group Description	Mycophenolate Mofetil Tablets, 500 mg dosed in first period followed by CellCept® Tablets, 500 mg dosed in second period; sequence repeated in third and fourth periods.	CellCept® Tablets, 500 mg dosed in first period followed by Mycophenolate Mofetil Tablets, 500 mg dosed in second period; sequence repeated in third and fourth periods.	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	20 100%	20 100%	40 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	2 10%	2 5%
Male	20 100%	18 90%	38 95%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	12 60%	12 60%	24 60%
Black	5 25%	8 40%	13 32.5%
Asian	3 15%	0 0%	3 7.5%
Region of Enrollment (participants) [Number]
Canada	20 100%	20 100%	40 100%

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	Cellcept®
Arm/Group Description	Mycophenolate Mofetil Tablets, 500 mg dosed in any period	CellCept® Tablets, 500 mg dosed in any period
Measure Participants	37	37
Mean (Standard Deviation) [µg/mL]	11.0939 (6.3067)	11.1715 (4.7689)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mycophenolate Mofetil, Cellcept®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of Variance (PROC MIXED) were performed on the log-transformed AUCt, AUCinf and Cmax parameters.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	93.97
	Confidence Interval	() 90%; 80.25 to 110.04
	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 the 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	Cellcept®
Arm/Group Description	Mycophenolate Mofetil Tablets, 500 mg dosed in any period	CellCept® Tablets, 500 mg dosed in any period
Measure Participants	37	37
Mean (Standard Deviation) [µg*hr/mL]	26.6752 (6.7137)	26.7354 (7.1533)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mycophenolate Mofetil, Cellcept®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analyses of Variance (PROC MIXED) were performed on the log-transformed AUCt, AUCinf and Cmax parameters.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	102.01
	Confidence Interval	() 90%; 98.74 to 105.39
	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 the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)
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	Cellcept®
Arm/Group Description	Mycophenolate Mofetil Tablets, 500 mg dosed in any period	CellCept® Tablets, 500 mg dosed in any period
Measure Participants	37	37
Mean (Standard Deviation) [µg*hr/mL]	25.2539 (6.6843)	25.3253 (6.8009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mycophenolate Mofetil, Cellcept®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analyses of Variance (PROC MIXED) were performed on the log-transformed AUCt, AUCinf and Cmax parameters.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	99.91
	Confidence Interval	() 90%; 95.99 to 103.98
	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.

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