Mycophenolate Mofetil Pharmacokinetics in Systemic Sclerosis

NCT03678987 | Completed DMC FDA Drug

• 1 other identifier: 2018-002105-54
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

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

Conditions

Systemic Sclerosis; Gastrointestinal Complication

Keywords

pharmacokinetics; mycophenolate mofetil

Outcome Measures

Primary Outcomes (1)

• Individual plasma concentrations of mycophenolic acid

  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).

  1 day

Secondary Outcomes (5)

• Correlation between F-calprotectin and the AUC of P-MPA

  1 day

• Correlation between the USCLA SCTC GIT-2.0 questionnaire and the AUC of P-MPA

  1 day

• Correlation between the Malnutrition Universal Screening Tool (MUST) and the AUC of P-MPA

  1 day

• Correlation between the precense of dysbiosis, as defined by the GA-MAP Dysbiosis Test and the AUC of P-MPA

  1 day

• Association between the AUC of P-MPA and the concomitant medication with a) NSAID, b) proton-pump inhibitors and c) Ca-channel blockers

  1 day

Study Arms (1)

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; Drug: mycophenolic acid

Interventions

P-MPA concentration DIAGNOSTIC_TEST

We will calculate AUC\_0-12 of MPA based on 4 measurements of P-MPA

SSc on MMF

mycophenolic acid DRUG

Patient will ingest mycophenolic acid as prescribed by their physician under the surveillance of an investigator.

Also known as: cellcept, mycophenolate mofetil

SSc on MMF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with systemic sclerosis using a stable dose of mycophenolate mofetil.

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Region Skane: lead

Study Sites (1)

Reumatologi SUS Lund, Region Skåne

Lund, 221 85, Sweden

Location

Related Publications (4)

• Volkmann ER, Tashkin DP, Li N, Roth MD, Khanna D, Hoffmann-Vold AM, Kim G, Goldin J, Clements PJ, Furst DE, Elashoff RM. Mycophenolate Mofetil Versus Placebo for Systemic Sclerosis-Related Interstitial Lung Disease: An Analysis of Scleroderma Lung Studies I and II. Arthritis Rheumatol. 2017 Jul;69(7):1451-1460. doi: 10.1002/art.40114. Epub 2017 May 23.

  PMID: 28376288 BACKGROUND

• McCune WJ, Al Abbas M. Mycophenolate mofetil, for rheumatic diseases: should we monitor the area under the curve? Curr Opin Rheumatol. 2018 May;30(3):229-230. doi: 10.1097/BOR.0000000000000501. No abstract available.

  PMID: 29538009 BACKGROUND

• Abd Rahman AN, Tett SE, Staatz CE. How accurate and precise are limited sampling strategies in estimating exposure to mycophenolic acid in people with autoimmune disease? Clin Pharmacokinet. 2014 Mar;53(3):227-245. doi: 10.1007/s40262-013-0124-z.

  PMID: 24327238 BACKGROUND

• de Winter BC, Neumann I, van Hest RM, van Gelder T, Mathot RA. Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease. Ther Drug Monit. 2009 Jun;31(3):382-90. doi: 10.1097/FTD.0b013e3181a23f1a.

  PMID: 19363460 BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic

Interventions

Mycophenolic Acid

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Kristofer Andréasson, MD PhD

  Region Skane

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: September 20, 2018
• Study Start: September 13, 2018
• Primary Completion: January 1, 2020
• Study Completion: February 1, 2020
• Last Updated: March 13, 2020

Record last verified: 2020-03

Locations

SE (1)