Pediatric Liver TransplantationPhase 2NCT02630563
Safety, Tolerability and Pharmacokinetics of Oral CellCept (Mycophenolate Mofetil) in Pediatric Liver Transplant Recipients on Concomitant Treatment With Cyclosporine and Corticosteroids
A Phase 2 study testing Corticosteroids, Cyclosporine and mycophenolate mofetil in people with Pediatric Liver Transplantation, run by Hoffmann-La Roche at 2 sites in United States.
Trial summary
The study is planned to be conducted in 2 parts. The first part (open label, multi-center, non-controlled) of the study will estimate a dose that would provide a mycophenolic acid (MPA) exposure in pediatric participant that is comparable to that achieved in adult liver transplant participants receiving the approved… Read more about this study
- Who is it for?
- Ages 3 months to 12 years
- Conditions the study is for
- Pediatric Liver Transplantation
- What is being tested?
- Corticosteroids, Cyclosporine and mycophenolate mofetil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2003to Jan 2005
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 months to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female participant must be between 3 months and 12 years of age
- Participant is a recipient of a first liver allograft from cadaveric or living donors
- Participant is a single-organ recipient (liver only)
- Female participants of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli International Units per milliliter (mIU/mL) within one week prior to PK sampling
- Female participants of childbearing potential must use two reliable forms of contraception simultaneously unless abstinence is the chosen method
- Effective contraception must be used before beginning of PK sampling
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- Participants must be able to receive oral medication
- Participants must be at least 6 months post-transplant and had started on MMF in the early post-transplant period (within 2 weeks of transplant)
- Participants must be receiving stable doses of MMF per center practice for at least 7 days prior to PK sampling
- In addition, participants must be receiving stable doses of cyclosporine and corticosteroids, according to center practice
- Participants' parent/guardian are capable of understanding the purposes and risks of the study and must sign an informed consent for the study
Who cannot join
- Pregnant or nursing adolescents
- Participants who had undergone dialysis within two weeks before PK sampling
- Participants with active systemic infections
- Participants with absolute neutrophil counts (ANC) of less than 1300 per microliter (µL), or platelets counts less than 50 000/µL or hemoglobin at a concentration below a set lower limit (according to center practice, but not less than 8 grams per deciliter) at the time of study entry
- Participants with active peptic ulcer disease
- Participants with severe diarrhea (more than 5 watery stools per day) or other gastrointestinal disorders which might interfere with their ability to absorb oral medication
- History of positive human immunodeficiency virus (HIV) test
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Study site
New York, New York, 10032-3784
Study site
San Francisco, California, 94143-0116
About this study
Official title: A Study of the Safety, Tolerability and Pharmacokinetics of Oral CellCept® (Mycophenolate Mofetil, MMF) in Pediatric Liver Transplant Recipients on Concomitant Treatment With Cyclosporine and Corticosteroids
The study is planned to be conducted in 2 parts. The first part (open label, multi-center, non-controlled) of the study will estimate a dose that would provide a mycophenolic acid (MPA) exposure in pediatric participant that is comparable to that achieved in adult liver transplant participants receiving the approved dose of mycophenolate mofetil (MMF, CellCept). The second part (open-label, multi-center, single-arm Phase IV study) of the study will provide the pharmacokinetics, efficacy and safety profile of the proposed dose in the immediate post-transplant period. This study will be conducted at two centers based in the United States of America. Twelve pediatric transplant participants receiving a first liver allograft from a cadaveric or living donor will be enrolled in this study. Stable pediatric liver transplant participants who are at least 6 months post-transplant and who were already receiving stable dose of MMF in combination with cyclosporine will be enrolled into the study. Participants should have received stable MMF dose according to center practice for at least seven days in order to get steady state pharmacokinetics (PK). Participants also should have received stable concomitant doses of cyclosporine (for at least 2 days) and corticosteroids per center practice. Participants will be aged between 9 months and 12 years, with at least 6 participants greater than or equal to (>/=) 9 months and less than (<) 36 months, of whom at least 2 will be <24 months.
- Conditions
- Pediatric Liver Transplantation
- Being tested
- Corticosteroids, Cyclosporine, mycophenolate mofetil
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CorticosteroidsDrug
Corticosteroids will be administered as per center practice. The choice of corticosteroid drug will also be based on center practice.
CyclosporineDrug
Cyclosporine will be administered as per center practice.
Also called CellCept
Part 1: Mycophenolate mofetil will be administered as per center practice. Part 2: Mycophenolate mofetil will be administered as per dose determined in Part 1.
| Study group | Role | What they receive |
|---|---|---|
| Mycophenolate Mofetil+Corticosteroids+Cyclosporine | Experimental | Part 1: Participants will receive mycophenolate mofetil. Part 2: Participants will receive mycophenolate mofetil along with cyclosporine and corticosteroids. Receives: Drug: Corticosteroids; Drug: Cyclosporine; Drug: mycophenolate mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours of Mycophenolic Acid Normalized for Dose And for Body Surface Area
The area under the plasma concentration-time curve from time zero to twelve hours (AUC [0-12h]) is area under the plasma concentration-time curve from time zero through 12 hours. AUC (0-12) hours was computed using the linear trapezoidal rule. For the calculations of AUC (0-12h), concentrations below the limit of quantification were assigned a value of zero if they occurred at the beginning of a profile. When such values appeared at the end of a profile they were assigned as missing data. AUC0-12h was normalized to 600 milligram per square meter (mg/m^2) and 1.5 gram. AUC was reported in microgram hour per milliliter (mcg*h/mL).
Measured: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months
Secondary outcomes (5)
Area Under the Plasma Concentration Time Curve From 0-12 Hours for Mycophenolic Acid and Mycophenolic Acid Glucuronide Phenolic Glucuronide of Mycophenolic Acid
The area under the plasma concentration-time curve from time zero to twelve hours (AUC [0-12h]) is area under the plasma concentration-time curve from time zero through 12 hours. AUC (0-12) hours was computed using the linear trapezoidal rule. For the calculations of AUC (0-12h), concentrations below the limit of quantification were assigned a value of zero if they occurred at the beginning of a profile. When such values appeared at the end of a profile they were assigned as missing data. AUC was reported in microgram hour per milliliter (mcg*h/mL).
Measured: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months
Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide
The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration. Cmax was obtained directly from the measured plasma concentration-time curves.
Measured: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants > 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants < 24 months
Time to Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide
Tmax is the amount of time after dosing to when the maximum concentration of MPA and MPAG was achieved.
Measured: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants > 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants < 24 months
Number of Participants With Adverse Events and Serious Adverse Events
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event.
Measured: Up to Day 32
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point
Mycophenolic Acid Glucuronide (MPAG) is an active metabolite of Mycophenolic Acid (MPA).
Measured: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2015 (estimated)
- Study startMay 2003
- Primary completionJan 2005
- Study completionJan 2005
Why it stopped: Due to extremely slow recruitment, infrequent use of combination triple therapy (MMF, cyclosporine, steroids), study was discontinued; Part 2 was not conducted.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pediatric Liver TransplantationStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study chair, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02630563
- Sponsor's protocol ID
- PA16497
- Status last verified
- Dec 2015
- First submitted
- 11 Dec 2015
- Last updated
- 19 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of the Safety, Tolerability and Pharmacokinetics of Oral CellCept® (Mycophenolate Mofetil, MMF) in Pediatric Liver Transplant Recipients on Concomitant Treatment With Cyclosporine and Corticosteroids
- ClinicalTrials.gov ID
- NCT02630563
- Acronym / sponsor ID
- PA16497
- Conditions
- Pediatric Liver Transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to extremely slow recruitment, infrequent use of combination triple therapy (MMF, cyclosporine, steroids), study was discontinued; Part 2 was not conducted.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- May 2003
- Primary completion
- Jan 2005 (actual)
- Study completion
- Jan 2005 (actual)
- First posted
- 15 Dec 2015 (estimated)
- Results
- Posted 12 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study is planned to be conducted in 2 parts. The first part (open label, multi-center, non-controlled) of the study will estimate a dose that would provide a mycophenolic acid (MPA) exposure in pediatric participant that is comparable to that achieved in adult liver transplant participants receiving the approved dose of mycophenolate mofetil (MMF, CellCept). The second part (open-label, multi-center, single-arm Phase IV study) of the study will provide the pharmacokinetics, efficacy and safety profile of the proposed dose in the immediate post-transplant period. This study will be conducted at two centers based in the United States of America. Twelve pediatric transplant participants receiving a first liver allograft from a cadaveric or living donor will be enrolled in this study. Stable pediatric liver transplant participants who are at least 6 months post-transplant and who were already receiving stable dose of MMF in combination with cyclosporine will be enrolled into the study. Participants should have received stable MMF dose according to center practice for at least seven days in order to get steady state pharmacokinetics (PK). Participants also should have received stable concomitant doses of cyclosporine (for at least 2 days) and corticosteroids per center practice. Participants will be aged between 9 months and 12 years, with at least 6 participants greater than or equal to (>/=) 9 months and less than (<) 36 months, of whom at least 2 will be <24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mycophenolate Mofetil+Corticosteroids+Cyclosporine | Experimental | Drug: Corticosteroids, Drug: Cyclosporine, Drug: mycophenolate mofetilPart 1: Participants will receive mycophenolate mofetil. Part 2: Participants will receive mycophenolate mofetil along with cyclosporine and corticosteroids. |
Who may qualify
- Ages
- 3 months to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- Male or female participant must be between 3 months and 12 years of age
- Participant is a recipient of a first liver allograft from cadaveric or living donors
- Participant is a single-organ recipient (liver only)
- Female participants of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli International Units per milliliter (mIU/mL) within one week prior to PK sampling
- Female participants of childbearing potential must use two reliable forms of contraception simultaneously unless abstinence is the chosen method
Key exclusion criteria (7 listed)
- Pregnant or nursing adolescents
- Participants who had undergone dialysis within two weeks before PK sampling
- Participants with active systemic infections
- Participants with absolute neutrophil counts (ANC) of less than 1300 per microliter (µL), or platelets counts less than 50 000/µL or hemoglobin at a concentration below a set lower limit (according to center practice, but not less than 8 grams per deciliter) at the time of study entry
- Participants with active peptic ulcer disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CorticosteroidsCorticosteroids will be administered as per center practice. The choice of corticosteroid drug will also be based on center practice. | Drug | Mycophenolate Mofetil+Corticosteroids+Cyclosporine |
| CyclosporineCyclosporine will be administered as per center practice. | Drug | Mycophenolate Mofetil+Corticosteroids+Cyclosporine |
| mycophenolate mofetilAlso: CellCeptPart 1: Mycophenolate mofetil will be administered as per center practice. Part 2: Mycophenolate mofetil will be administered as per dose determined in Part 1. | Drug | Mycophenolate Mofetil+Corticosteroids+Cyclosporine |
Primary outcome
Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours of Mycophenolic Acid Normalized for Dose And for Body Surface Area
Time frame: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months
The area under the plasma concentration-time curve from time zero to twelve hours (AUC [0-12h]) is area under the plasma concentration-time curve from time zero through 12 hours. AUC (0-12) hours was computed using the linear trapezoidal rule. For the calculations of AUC (0-12h), concentrations below the limit of quantification were assigned a value of zero if they occurred at the beginning of a profile. When such values appeared at the end of a profile they were assigned as missing data. AUC0-12h was normalized to 600 milligram per square meter (mg/m^2) and 1.5 gram. AUC was reported in microgram hour per milliliter (mcg*h/mL).
5 secondary outcomes
Area Under the Plasma Concentration Time Curve From 0-12 Hours for Mycophenolic Acid and Mycophenolic Acid Glucuronide Phenolic Glucuronide of Mycophenolic Acid
Time frame: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months
Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide
Time frame: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants > 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants < 24 months
Time to Maximum Plasma Concentration for Mycophenolic Acid and Mycophenolic Acid Glucuronide
Time frame: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants > 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants < 24 months
Number of Participants With Adverse Events and Serious Adverse Events
Time frame: Up to Day 32
Plasma Concentration of Mycophenolic Acid and Its Metabolite Mycophenolic Acid Glucuronide at Each Time Point
Time frame: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study chair
Hoffmann-La Roche
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Corticosteroids, Cyclosporine and mycophenolate mofetil in people with Pediatric Liver Transplantation, run by Hoffmann-La Roche at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area Under the Plasma Concentration-Time Curve From 0 to 12 Hours of Mycophenolic Acid Normalized for Dose And for Body Surface Area (time frame: Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, and 12.0 hours post oral dosing for participants greater than (>) 24 months, and at pre-dose, 0.75, 2.0, 4.0 and 12.0 hours post oral dosing for participants less than (<) 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2016.