Mycophenolate Mofetil Pharmacokinetics in Systemic Sclerosis (MMFSSC)
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|ClinicalTrials.gov Identifier: NCT03678987|
Recruitment Status : Enrolling by invitation
First Posted : September 20, 2018
Last Update Posted : September 25, 2018
Drug of investigation: Mycophenolate mofetil (MMF), given orally as a tablet twice daily.
Dosage of drug: This study recruits patients who have been prescribed a steady dose of MMF in the range between 1000 and 3000 mg daily by their physician.
Design: This is an open-label PK study.
Disease studied: Systemic sclerosis (SSC, scleroderma).
Variables assessed: Estimated AUC0-12 for MMF. Gastrointestinal manifestations of SSc. Concomitant medication.
Inclusion criteria: Diagnosis of SSC fulfilling the 2013 classification criteria for this disease. Participant should have been prescribed a stable dose of MMF tablets, taken twice daily, for at least 3 months prior to the study.
Exclusion criteria: Failure to comply with study protocol. Limited access to repeated venous puncture. Recipient of organ transplant. Pulmonary arterial hypertension.
Number of participants: The study aims at the inclusion of 35 subjects.
Primary objective: To investigate the PK of orally ingested MMF in SSC.
- To investigate how SSC manifested in the gastrointestinal (GI) tract may alter the PK of MMF.
- To investigate how the PK of MMF in SSc is altered by medications often used in SSC, i.e. proton pump inhibitors (PPI), NSAID and calcium channel blockers.
|Condition or disease||Intervention/treatment|
|Systemic Sclerosis Gastrointestinal Complication||Diagnostic Test: P-MPA concentration Drug: mycophenolic acid|
DESIGN AND ASSESSMENT SCHEDULE Study participants will take their medication, including the study drug, as prescribed by their ordinary physician. Study participant will note what they had for breakfast.
The study-timespan for the individual study participant is estimated to maximum 8 hours.
Blood samples will be drawn from a subcutaneous venous port if available. If not available, subjects will be receive a peripheral venous catheter that is to be used for repeated blood sampling. If usage of such a catheter fails during the study day, blood samples will be drawn from repeated venipunctures.
The following variables will be studied:
Plasma-MMF-concentration: Will be measured by approved laboratory, Skåne UniversityHospital, using high performance liquid chromatography. AUC 0_12 will be calculated as suggested by de Winter, Neumann, van Hest et. al., Ther Drug Mon 2009;31(3):382-390.
Kidney and liver function: Serum samples will be analysed regarding kidney function and eGFR will be calculated from creatinin and cystatin C. Liver function will be assessed by AST, ALT, GT and ALP. Hematological characteristics will be noted.
GI manifestations of SSc: Fecal calprotectin, will be assayed by ELISA (Calpro, Lysaker, Norway) at University Hospital Lund. Malnutrition will evaluated in reference to the validated Malnutrition Universal Screening Tool (MUST). S-transthyretin, vitamin B12, folic acid, iron and zink and S-albumin will be assessed as markers of malnutrition. The intestinal flora will be assessed by microbiological analysis of fecal sampling (Genetic Analysis AS, Oslo, Norway).
Pregnancy: Will be evaluated by urine test.
Questionnaire: Regarding concomitant medication and the UCLA SCTC GIT 2.0 (Swedish version) will be given to each study participant.
|Study Type :||Observational|
|Estimated Enrollment :||35 participants|
|Official Title:||Mycophenolate Mofetil in Systemic Sclerosis: A Phase 1 Pharmacokinetic Study of Orally Ingested Mycophenolate Mofetil Tablets in Patients Suffering From Systemic Sclerosis|
|Actual Study Start Date :||September 13, 2018|
|Estimated Primary Completion Date :||January 1, 2020|
|Estimated Study Completion Date :||February 1, 2020|
SSc on MMF
Patients with systemic sclerosis using mycophenolate mofetil (mycophenolic acid, MMF) since >3 months.
During a 6 hour time period, P-MPA concentration will be measured 4 times.
Diagnostic Test: P-MPA concentration
We will calculate AUC_0-12 of MPA based on 4 measurements of P-MPA
Drug: mycophenolic acid
Patient will ingest mycophenolic acid as prescribed by their physician under the surveillance of an investigator.
- Individual plasma concentrations of mycophenolic acid [ Time Frame: 1 day ]By 4 measurements of P-MPA during a 6 hour time period we will estimate the individual drug exposition expressed as Area Under the Curve (AUC) 0-12 for this medicine and calculated as suggested by Abd Rahman 2014 (reference 3).
- Correlation between F-calprotectin and the AUC of P-MPA [ Time Frame: 1 day ]To investigate how gastrointestinal inflammation as measured by F-calprotectin correlate with the AUC of P-MPA
- Correlation between the USCLA SCTC GIT-2.0 questionnaire and the AUC of P-MPA [ Time Frame: 1 day ]To investigate how the gastrointestinal manifestations of SSc, assessed by a SSc-specific questionnaire, correlate with the AUC of P-MPA
- Correlation between the Malnutrition Universal Screening Tool (MUST) and the AUC of P-MPA [ Time Frame: 1 day ]To investigate if malnutrition, assessed by the MUST, correlate with the AUC of P-MPA
- Correlation between the precense of dysbiosis, as defined by the GA-MAP Dysbiosis Test and the AUC of P-MPA [ Time Frame: 1 day ]To investigate if intestinal dysbiosis, assessed by the a validated test available through Genetic Analysis, Oslo Norway, is associated with the AUC of P-MPA
- Association between the AUC of P-MPA and the concomitant medication with a) NSAID, b) proton-pump inhibitors and c) Ca-channel blockers [ Time Frame: 1 day ]To compare the AUC of P-MPA in patients with and without the above mentionened concomitant medication
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03678987
|Reumatologi SUS Lund, Region Skåne|
|Lund, Sweden, 221 85|
|Principal Investigator:||Kristofer Andréasson, MD PhD||Region Skane|