Trial Outcomes & Findings for Influence of Pantoprazole on the Bioavailability of MMF and EC-MPS (NCT NCT01801280)
NCT ID: NCT01801280
Last Updated: 2019-02-21
Results Overview
Bioavailability (12h AUC) of mycophenolic acid in renal transplant patients after administration of MMF+/-PAN and EC-MPS+/-PAN For evaluation of pharmacokinetic and pharmacodynamic parameters blood will be collected before, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h after drug intake.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
20 participants
Primary outcome timeframe
Study duration for each patient: 2 months. After 10-14 days of drug intake blood samples for PK/PD analysis will be collected. On the next day new treatment starts. There are 4 study visits at the study center. Duration will be approximately 12hours
Results posted on
2019-02-21
Participant Flow
Recruitment lastet between January 2012 - March 2013.
Participant milestones
| Measure |
Sequence A
1. st period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
2. nd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
3. rd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
4. th period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
|
Sequence B
1. st period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
2. nd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
3. rd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
4. th period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
|
Sequence C
1. st period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
2. nd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
3. rd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
4. th period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
|
Sequence D
1. st period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
2. nd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
3. rd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
4. th period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
|
|---|---|---|---|---|
|
Period 1
STARTED
|
5
|
5
|
5
|
5
|
|
Period 1
COMPLETED
|
5
|
4
|
5
|
5
|
|
Period 1
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
Period 2
STARTED
|
5
|
4
|
5
|
5
|
|
Period 2
COMPLETED
|
4
|
4
|
5
|
5
|
|
Period 2
NOT COMPLETED
|
1
|
0
|
0
|
0
|
|
Period 3
STARTED
|
4
|
4
|
5
|
5
|
|
Period 3
COMPLETED
|
4
|
4
|
5
|
5
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4
STARTED
|
4
|
4
|
5
|
5
|
|
Period 4
COMPLETED
|
4
|
4
|
4
|
5
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Sequence A
1. st period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
2. nd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
3. rd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
4. th period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
|
Sequence B
1. st period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
2. nd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
3. rd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
4. th period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
|
Sequence C
1. st period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
2. nd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
3. rd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
4. th period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
|
Sequence D
1. st period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
2. nd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
3. rd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
4. th period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
|
|---|---|---|---|---|
|
Period 1
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
|
Period 2
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
Period 4
Protocol Violation
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Influence of Pantoprazole on the Bioavailability of MMF and EC-MPS
Baseline characteristics by cohort
| Measure |
Sequence A
n=5 Participants
1. st period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
2. nd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
3. rd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
4. th period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
|
Sequence B
n=5 Participants
1. st period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
2. nd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
3. rd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
4. th period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
|
Sequence C
n=5 Participants
1. st period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
2. nd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
3. rd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
4. th period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
|
Sequence D
n=5 Participants
1. st period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
2. nd period: Mycophenolate mofetil (MMF) tablet (500, 750 or 1000mg) b.i.d. every 12 hours for 10-14d.
3. rd period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d.
4. th period: Mycophenolate sodium (EC-MPS) tablet (720, 1080, 1440) b.i.d. every 12 hours for 10-14d. Pantoprazole 40mg tablet (PAN) each for 10-14d.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
59 y
STANDARD_DEVIATION 12 • n=99 Participants
|
42 y
STANDARD_DEVIATION 14 • n=107 Participants
|
33 y
STANDARD_DEVIATION 17 • n=206 Participants
|
43 y
STANDARD_DEVIATION 14 • n=7 Participants
|
44 y
STANDARD_DEVIATION 16 • n=31 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
12 Participants
n=31 Participants
|
|
Age at study enrollment
|
63 years
STANDARD_DEVIATION 11 • n=99 Participants
|
46 years
STANDARD_DEVIATION 16 • n=107 Participants
|
44 years
STANDARD_DEVIATION 15 • n=206 Participants
|
51 years
STANDARD_DEVIATION 19 • n=7 Participants
|
51 years
STANDARD_DEVIATION 16 • n=31 Participants
|
PRIMARY outcome
Timeframe: Study duration for each patient: 2 months. After 10-14 days of drug intake blood samples for PK/PD analysis will be collected. On the next day new treatment starts. There are 4 study visits at the study center. Duration will be approximately 12hoursBioavailability (12h AUC) of mycophenolic acid in renal transplant patients after administration of MMF+/-PAN and EC-MPS+/-PAN For evaluation of pharmacokinetic and pharmacodynamic parameters blood will be collected before, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h after drug intake.
Outcome measures
| Measure |
Mycophenolate Mofetil (MMF)
n=17 Participants
Mycophenolate mofetil (MMF) tablet twice a day every 12 hours for two weeks.
Mycophenolate mofetil daily dose: 1000mg, 1500mg, 2000mg.
|
MMF+PAN
n=17 Participants
Mycophenolate mofetil (MMF) tablet twice a day every 12 hours for two weeks.
Mycophenolate mofetil daily dose: 1000mg, 1500mg, 2000mg.
Pantoprazole daily dose: 40mg once in the morning together with Mycophenolate mofetil.
Pantoprazole tablet (PAN) once a day in the morning for two weeks.
|
EC-MPS
n=17 Participants
Mycophenolate sodium (EC-MPS) tablet twice a day every 12 hours for two weeks.
Mycophenolate sodium daily dose: 720mg, 1080mg, 1440mg.
|
EC-MPS + PAN
n=17 Participants
Mycophenolate sodium (EC-MPS) tablet twice a day every 12 hours for two weeks.
Mycophenolate sodium daily dose: 720mg, 1080mg, 1440mg.
Pantoprazole daily dose: 40mg once in the morning together with Mycophenolate sodium.
Pantoprazole tablet (PAN) once a day in the morning for two weeks.
|
|---|---|---|---|---|
|
Dose-normalized AUC of Mycophenolic Acid
|
41 mg*h/L
Standard Deviation 18
|
38 mg*h/L
Standard Deviation 18
|
43 mg*h/L
Standard Deviation 19
|
46 mg*h/L
Standard Deviation 18
|
Adverse Events
Mycophenolate Mofetil (MMF)
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
MMF + PAN
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
EC-MPS
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
EC-MPS + PAN
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Mycophenolate Mofetil (MMF)
n=19 participants at risk
Mycophenolate mofetil (MMF) tablet twice a day every 12 hours for two weeks.
Mycophenolate mofetil daily dose: 1000mg, 1500mg, 2000mg.
|
MMF + PAN
n=18 participants at risk
Mycophenolate mofetil (MMF) tablet twice a day every 12 hours for two weeks.
Mycophenolate mofetil daily dose: 1000mg, 1500mg, 2000mg.
Pantoprazole daily dose: 40mg once in the morning together with Mycophenolate mofetil.
Pantoprazole tablet (PAN) once a day in the morning for two weeks.
|
EC-MPS
n=18 participants at risk
Mycophenolate sodium (EC-MPS) tablet twice a day every 12 hours for two weeks.
Mycophenolate sodium daily dose: 720mg, 1080mg, 1440mg.
|
EC-MPS + PAN
n=18 participants at risk
Mycophenolate sodium (EC-MPS) tablet twice a day every 12 hours for two weeks.
Mycophenolate sodium daily dose: 720mg, 1080mg, 1440mg.
Pantoprazole daily dose: 40mg once in the morning together with Mycophenolate sodium.
Pantoprazole tablet (PAN) once a day in the morning for two weeks.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Noro virus infection
|
5.3%
1/19 • Number of events 1 • Adverse event data were collected at every study visit. No follow up data.
|
0.00%
0/18 • Adverse event data were collected at every study visit. No follow up data.
|
0.00%
0/18 • Adverse event data were collected at every study visit. No follow up data.
|
0.00%
0/18 • Adverse event data were collected at every study visit. No follow up data.
|
|
Renal and urinary disorders
Urinary tract infection
|
0.00%
0/19 • Adverse event data were collected at every study visit. No follow up data.
|
5.6%
1/18 • Number of events 1 • Adverse event data were collected at every study visit. No follow up data.
|
0.00%
0/18 • Adverse event data were collected at every study visit. No follow up data.
|
0.00%
0/18 • Adverse event data were collected at every study visit. No follow up data.
|
Other adverse events
| Measure |
Mycophenolate Mofetil (MMF)
n=19 participants at risk
Mycophenolate mofetil (MMF) tablet twice a day every 12 hours for two weeks.
Mycophenolate mofetil daily dose: 1000mg, 1500mg, 2000mg.
|
MMF + PAN
n=18 participants at risk
Mycophenolate mofetil (MMF) tablet twice a day every 12 hours for two weeks.
Mycophenolate mofetil daily dose: 1000mg, 1500mg, 2000mg.
Pantoprazole daily dose: 40mg once in the morning together with Mycophenolate mofetil.
Pantoprazole tablet (PAN) once a day in the morning for two weeks.
|
EC-MPS
n=18 participants at risk
Mycophenolate sodium (EC-MPS) tablet twice a day every 12 hours for two weeks.
Mycophenolate sodium daily dose: 720mg, 1080mg, 1440mg.
|
EC-MPS + PAN
n=18 participants at risk
Mycophenolate sodium (EC-MPS) tablet twice a day every 12 hours for two weeks.
Mycophenolate sodium daily dose: 720mg, 1080mg, 1440mg.
Pantoprazole daily dose: 40mg once in the morning together with Mycophenolate sodium.
Pantoprazole tablet (PAN) once a day in the morning for two weeks.
|
|---|---|---|---|---|
|
Immune system disorders
Common cold
|
21.1%
4/19 • Number of events 4 • Adverse event data were collected at every study visit. No follow up data.
|
16.7%
3/18 • Number of events 3 • Adverse event data were collected at every study visit. No follow up data.
|
11.1%
2/18 • Number of events 2 • Adverse event data were collected at every study visit. No follow up data.
|
11.1%
2/18 • Number of events 2 • Adverse event data were collected at every study visit. No follow up data.
|
Additional Information
Olesja Rissling
Charité University Hospital - Department of Nephrology
Phone: +49 30 450 514 153
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place