A Pharmacokinetic Study of CellCept (Mycophenolate Mofetil) Versus Mycophenolate Sodium in Kidney Transplant Patients

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01033864
• Collaborator: (none)
• Enrollment: 23
• Location: 1
• Arms: 2
• Duration (Months): 7
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

This open-label, 2-arm study will compare the pharmacokinetics of CellCept and mycophenolate sodium in kidney transplanted patients on a calcineurininhibitor-free mycophenolic acid-based therapy. On the study day patients will take their prescribed medication (either CellCept or mycophenolate sodium). Blood samples will be drawn directly before and at intervals up to 12 hours after intake of the study medication. Anticipated time on study treatment is 12 hours and target sample size is 24.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Drug: MMF; Drug: EC-MPS; Drug: Prednisone	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of Pharmocokinetics of Mycophenolate Mofetil and Enteric Coated Mycophenolate Sodium in Calcineurininhibitor-free Treated Patients After Renal Transplantation
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Jun 1, 2010
• Actual Study Completion Date: Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MMF, Prednisone Participants received mycophenolate mofetil (MMF) orally (PO) at a dose of 1 gram per day (g/day) twice daily (BID), and prednisone, PO, up to 5 milligrams per day (mg/day) for at least 1 month.	Drug: MMF; 1 g per day b.i.d. p.o. for at least 1 month; Other Names: CellCept mycophenolate mofetil ; Drug: Prednisone; 5 mg per day p.o.
Active Comparator: EC-MPS Participants received mycophenolate sodium (EC-MPS), PO, at a dose of 720 mg/day BID, and prednisone PO up to 5 mg/day for at least 1 month.	Drug: EC-MPS; 720 mg b.i.d. p.o. for at least 1 month; Other Names: mycophenolate sodium ; Drug: Prednisone; 5 mg per day p.o.

Outcome Measures

Primary Outcome Measures

1. Pre-dose Trough Concentration (C0) [Day 1 predose]

   The mean mycophenolic acid (MPA) concentration in plasma was determined (in milligrams per liter [mg/L]) from blood samples collected predose (immediately before receiving study treatment).

2. Dose-Normalized C0 [Day 1 predose]

   Dose normalized C0 was determined (in mg/L) from blood samples collected predose. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized C0 equals (=) C0 divided by (/) (actual dose taken/1000) For the EC-MPS group: Dose normalized C0 = C0 / (actual dose taken/720)

3. Minimum Plasma Concentration (Cmin) [Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours]

   The mean minimum MPA concentration in plasma was determined (in mg/L) from blood samples collected predose and postdose on Day 1.

4. Dose-Normalized Cmin [Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours]

   Dose-normalized Cmin was determined (in mg/L) from blood samples collected predose and postdose. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized Cmin = Cmin/ (actual dose taken/1000) For the EC-MPS group: Dose normalized Cmin = Cmin / (actual dose taken/720)

5. Maximum Plasma Concentration (Cmax) [Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours]

   The mean maximum MPA concentration in plasma was determined (in mg/L) in blood samples collected predose and postdose on Day 1.

6. Dose-Normalized Cmax (mg/L) [Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours]

   Dose-normalized Cmax in plasma was determined (in mg/L) from blood samples collected predose and postdose on Day 1. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized Cmax = Cmax / (actual dose taken/1000) For the EC-MPS group: Dose normalized Cmax = Cmax / (actual dose taken/720)

7. MPA Area Under the Curve From 0 to 12 Hours (AUC0-12) [Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours]

   The mean MPA AUC0-12 in plasma was determined (in mg multiplied by hours, per Liter [mg*h/L]) from blood samples collected predose and postdose on Day 1.

8. Dose-Normalized MPA AUC0-12 [Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours]

   Dose-normalized MPA AUC0-12 in plasma was determined (mg*h/L) from blood samples collected predose and postdose on Day 1. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized MPA AUC = MPA AUC / (actual dose taken/1000) For the EC-MPS group: Dose normalized MPA AUC = MPA AUC / (actual dose taken/720)

9. Percentage of Participants By Time to Maximum Plasma Concentration (Tmax) [Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours]

Secondary Outcome Measures

1. Regression Coefficients For Participants Receiving MMF [Day 1 at 30 minutes and 1 and 2 hours postdose]

   The estimated regression coefficients for participants who received MMF presented in milligrams per liter (mg/L).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• adult patients, >/=18 years of age

• kidney transplantation >/=6 months ago

• on mycophenolic acid-based, calcineurininhibitor-free therapy for >/=3 months, >/=1 month on stable dose

• co-therapy with 5mg prednisone for >/=1 month

Exclusion Criteria:

• active gastrointestinal ulcus

• severe diarrhea od gastrointestinal disease

• severe impairment of renal function

• current malignancy

• Lesch-Nyhan- or Kelley-Seegmiller-Syndrome

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Frankfurt Am Main		Germany	60528

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01033864
• Other Study ID Numbers: ML22641; 2009-012355-15
• First Posted: Dec 17, 2009
• Last Update Posted: Aug 27, 2015
• Last Verified: Aug 1, 2015

• Additional relevant MeSH terms: Mycophenolic Acid; Prednisone

Study Results

Participant Flow

Arm/Group Title	Mycophenolate Mofetil (MMF)/Prednisone	Enteric-coated Mycophenolate Sodium (EC-MPS)/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, orally (PO), at a dose prescribed by their physician and prednisone up to 5 milligrams (mg) PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Period Title: Overall Study
STARTED	12	11
COMPLETED	12	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone	Total
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Total of all reporting groups
Overall Participants	12	11	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.5 (11.06)	58.0 (8.04)	59.8 (9.68)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	4 36.4%	9 39.1%
Male	7 58.3%	7 63.6%	14 60.9%

Outcome Measures

1. Primary Outcome

Title	Pre-dose Trough Concentration (C0)
Description	The mean mycophenolic acid (MPA) concentration in plasma was determined (in milligrams per liter [mg/L]) from blood samples collected predose (immediately before receiving study treatment).
Time Frame	Day 1 predose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population: all participants who took study drug and for whom all defined blood samples at the planned sampling time points were available.

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Mean (Standard Deviation) [mg/L]	2.387 (1.1327)	2.944 (2.2103)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8055
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Dose-Normalized C0
Description	Dose normalized C0 was determined (in mg/L) from blood samples collected predose. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized C0 equals (=) C0 divided by (/) (actual dose taken/1000) For the EC-MPS group: Dose normalized C0 = C0 / (actual dose taken/720)
Time Frame	Day 1 predose

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Mean (Standard Deviation) [mg/L]	2.962 (1.4439)	4.658 (3.1121)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2548
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	Minimum Plasma Concentration (Cmin)
Description	The mean minimum MPA concentration in plasma was determined (in mg/L) from blood samples collected predose and postdose on Day 1.
Time Frame	Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Mean (Standard Deviation) [mg/L]	1.385 (0.6061)	1.620 (0.6632)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4417
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Dose-Normalized Cmin
Description	Dose-normalized Cmin was determined (in mg/L) from blood samples collected predose and postdose. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized Cmin = Cmin/ (actual dose taken/1000) For the EC-MPS group: Dose normalized Cmin = Cmin / (actual dose taken/720)
Time Frame	Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Mean (Standard Deviation) [mg/L]	1.702 (0.8018)	2.613 (1.0291)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0455
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Primary Outcome

Title	Maximum Plasma Concentration (Cmax)
Description	The mean maximum MPA concentration in plasma was determined (in mg/L) in blood samples collected predose and postdose on Day 1.
Time Frame	Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Mean (Standard Deviation) [mg/L]	15.385 (5.2320)	17.827 (4.2898)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2300
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Primary Outcome

Title	Dose-Normalized Cmax (mg/L)
Description	Dose-normalized Cmax in plasma was determined (in mg/L) from blood samples collected predose and postdose on Day 1. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized Cmax = Cmax / (actual dose taken/1000) For the EC-MPS group: Dose normalized Cmax = Cmax / (actual dose taken/720)
Time Frame	Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Mean (Standard Deviation) [mg/L]	18.402 (5.4349)	29.996 (11.3229)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0106
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Primary Outcome

Title	MPA Area Under the Curve From 0 to 12 Hours (AUC0-12)
Description	The mean MPA AUC0-12 in plasma was determined (in mg multiplied by hours, per Liter [mg*h/L]) from blood samples collected predose and postdose on Day 1.
Time Frame	Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Mean (Standard Deviation) [mg*h/L]	50.36348 (15.423230)	57.06682 (10.965285)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3401
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Primary Outcome

Title	Dose-Normalized MPA AUC0-12
Description	Dose-normalized MPA AUC0-12 in plasma was determined (mg*h/L) from blood samples collected predose and postdose on Day 1. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized MPA AUC = MPA AUC / (actual dose taken/1000) For the EC-MPS group: Dose normalized MPA AUC = MPA AUC / (actual dose taken/720)
Time Frame	Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Mean (Standard Deviation) [mg*h/L]	61.53862 (21.003959)	94.65765 (29.307839)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0074
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

9. Primary Outcome

Title	Percentage of Participants By Time to Maximum Plasma Concentration (Tmax)
Time Frame	Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	MMF/Prednisone	EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.	Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12	11
Tmax equals (=) 0.5333 hours (hrs)	16.7 139.2%	0.0 0%
Tmax=0.6000 hrs	16.7 139.2%	0.0 0%
Tmax=0.7333 hrs	16.7 139.2%	0.0 0%
Tmax=0.7667 hrs	8.3 69.2%	0.0 0%
Tmax=1.0667 hrs	8.3 69.2%	9.1 82.7%
Tmax=1.0833 hrs	16.7 139.2%	0.0 0%
Tmax=1.1167 hrs	8.3 69.2%	0.0 0%
Tmax=1.2167 hrs	8.3 69.2%	0.0 0%
Tmax=2.0167 hrs	0.0 0%	9.1 82.7%
Tmax=2.0833 hrs	0.0 0%	18.2 165.5%
Tmax=2.1000 hrs	0.0 0%	9.1 82.7%
Tmax=2.1167 hrs	0.0 0%	27.3 248.2%
Tmax=2.1667 hrs	0.0 0%	9.1 82.7%
Tmax=3.1167 hrs	0.0 0%	9.1 82.7%
Tmax=3.1833 hrs	0.0 0%	9.1 82.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MMF/Prednisone, EC-MPS/Prednisone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

10. Secondary Outcome

Title	Regression Coefficients For Participants Receiving MMF
Description	The estimated regression coefficients for participants who received MMF presented in milligrams per liter (mg/L).
Time Frame	Day 1 at 30 minutes and 1 and 2 hours postdose

Outcome Measure Data

Analysis Population Description

PK population. Only participants in the MMF/Prednisone group were assessed for this outcome measure, n=12.

Arm/Group Title	MMF/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
Measure Participants	12
Intercept	2.17192
Concentration at 30 minutes (C0.5)	0.74031
Concentration at 1 hour (C1)	1.89323
Concentration at 2 hours (C2)	2.85923

Adverse Events

Time Frame	The observational period, approximately 13 hours.
Adverse Event Reporting Description	All randomized participants were included in the safety analysis.
Arm/Group Title	MMF/Prednisone		EC-MPS/Prednisone
Arm/Group Description	Participants were administered MMF tablets or capsules, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.		Participants were administered EC-MPS tablets, PO, at a dose prescribed by their physician and prednisone up to 5 mg PO on Day 1.
All Cause Mortality
	MMF/Prednisone		EC-MPS/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MMF/Prednisone		EC-MPS/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	MMF/Prednisone		EC-MPS/Prednisone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.