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Trial record 1 of 1200 for:    MYCOPHENOLIC ACID
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Mycophenolate Mofetil Pharmacokinetics in Systemic Sclerosis (MMFSSC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03678987
Recruitment Status : Completed
First Posted : September 20, 2018
Last Update Posted : March 13, 2020
Sponsor:
Information provided by (Responsible Party):
Kristofer Andreasson, Region Skane

Tracking Information
First Submitted Date September 13, 2018
First Posted Date September 20, 2018
Last Update Posted Date March 13, 2020
Actual Study Start Date September 13, 2018
Actual Primary Completion Date January 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 18, 2018)
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).
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: September 18, 2018)
  • 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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Mycophenolate Mofetil Pharmacokinetics in Systemic Sclerosis
Official Title Mycophenolate Mofetil in Systemic Sclerosis: A Phase 1 Pharmacokinetic Study of Orally Ingested Mycophenolate Mofetil Tablets in Patients Suffering From Systemic Sclerosis
Brief Summary

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.

Study population:

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.

Secondary objectives:

  1. To investigate how SSC manifested in the gastrointestinal (GI) tract may alter the PK of MMF.
  2. 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.
Detailed Description

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.

VARIABLES STUDIED

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
Study Design Observational Model: Other
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients with systemic sclerosis using a stable dose of mycophenolate mofetil.
Condition
  • Systemic Sclerosis
  • Gastrointestinal Complication
Intervention
  • 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.
    Other Names:
    • cellcept
    • mycophenolate mofetil
Study Groups/Cohorts 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.

Interventions:
  • Diagnostic Test: P-MPA concentration
  • Drug: mycophenolic acid
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: September 18, 2018)
35
Original Estimated Enrollment Same as current
Actual Study Completion Date February 1, 2020
Actual Primary Completion Date January 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • a confirmed diagnosis of SSC according to the 2013 ACR/EULAR classification criteria
  • above 18 years of age
  • fluent in Swedish and able to understand the study protocol and "Patient information"
  • being prescribed and using a fixed dos (1000-3000 mg daily) of MMF tablet, Cellcept or substitutable medical product, twice daily since at least 3 months
  • the study participant's written and informed consent
  • women in child-bearing age should use contraception

Exclusion Criteria:

  • Recipient of a solid organ transplant
  • Pregnancy or lactation
  • The presence of renal failure (defined as eGFR < 30 ml/min)
  • A history of complicated venipunctures defined as
  • a history of any venipuncture within the last year that required three or more attempts in order to succeed or
  • a decision has been made that the patient should receive a subcutaneous venous port because of complicated venipunctures.

If the patient has a functioning subcutaneous venous port, the above criteria does not apply if venous sampling has been uncomplicated from this port.

  • A history of hypersensitivity reactions to MMF
  • Patients diagnosed with any kind of acute infection during the one (1) week preceding the study day
  • A history of gastrointestinal surgery that includes resection of any port of the ventricle, small intestine, large intestine or liver (except for surgery for appendicitis, gall bladder resection or hemorrhoids, which do not constitute reasons for exclusion)
  • Pulmonary arterial hypertension
  • Anemia, defined as Hb < 100 g/L during the last 4 weeks The patient will be informed about the study and sign informed consent before study commences.
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Sweden
Removed Location Countries  
 
Administrative Information
NCT Number NCT03678987
Other Study ID Numbers 2018-002105-54
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement
Plan to Share IPD: Undecided
Plan Description: This issue will be discussed with the Ethical board.
Responsible Party Kristofer Andreasson, Region Skane
Study Sponsor Region Skane
Collaborators Not Provided
Investigators
Principal Investigator: Kristofer Andréasson, MD PhD Region Skane
PRS Account Region Skane
Verification Date March 2020