Clinical trial NCT02453997: Mycophenolic Acid Pharmacokinetics and Pharmacogenomics in Lupus Nephritis
Official title: Mycophenolic Acid Pharmacokinetics and Pharmacogenomics - Impact on the Clinical Outcomes of Patients With Severe Lupus Nephritis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lupus Nephritis
Keywords: lupus nephritis
mycophenolic acid
pharmacokinetics
pharmacogenomics
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: United Christian Hospital
First posted: 2015-05-27
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Lupus Nephritis patients (both active or remission)

Brief summary: This study investigate mycophenic acid (MPA) pharmacokinetics and pharmacogenomics and their impact on the clinical outcomes in lupus nephritis (LN) patients. Lupus nephritis patients (both active or inactive) will be recruited. MPA levels will be checked at 1, 2, 4, 8, 10, 12 hrs after MMF administration by an enzymatic assay upon recruitment, then at 6-months' intervals and also when clinically significant events occurred. The MPA levels will be correlated with clinical parameters and outcomes. Pharmacogenomics studies will also be carried out and correlated with MPA exposure and clinical outcomes.

Detailed description: This study investigate mycophenic acid (MPA) pharmacokinetics and pharmacogenomics and their impact on the clinical outcomes in lupus nephritis (LN) patients. Lupus nephritis patients (both active or inactive) will be recruited. MPA levels will be checked at 1, 2, 4, 8, 10, 12 hrs after MMF administration by an enzymatic assay upon recruitment, then at 6-months' intervals and also when clinically significant events occurred. The MPA levels will be correlated with clinical parameters and outcomes. For active patients, the MPA levels will be correlated with treatment response (CR or PR) and side effects. For patients in remission, the MPA levels will be correlated with drug tolerability and relapse. Pharmacogenomics studies will also be carried out and correlated with MPA exposure and clinical outcomes.

Eligibility criteria: Inclusion Criteria:

1. Patients with recent active LN (biopsy-proven Class III/IV+/-V LN according to the ISN/RPS 2003 classifications within 3 months, with proteinuria \>0.5 g/day and/or active urinary sediments) who receive corticosteroids and MMF (1g bd for 6 months) as induction treatment.
2. LN patients in remission (defined as proteinuria \<0.5 g/day with inactive urinary sediment, prednisolone \<10 mg/day) and on stable MMF maintenance (dose unchanged within the previous 3 months).

Exclusion Criteria:

1. Patients who receive enteric-coated mycophenolic acid (myfortic).
2. Patients who receive concomitant calcineurin inhibitors (e.g. cyclosporine or tacrolimus) other than corticosteroids and MMF.
3. Patients who receive concomitant medications which affect the MPA pharmacokinetics such as cholestyramine, acyclovir, and rifampicin.
4. Patients who are pregnant or lactating.
5. Patients with gastric emptying disorders
6. Patients with hepatic or biliary diseases

Primary outcomes:
measure: AUC (0-12)
timeFrame: 24 months
Secondary outcomes:
measure: Infection
timeFrame: 24 months
measure: Gastrointestinal disturbances
timeFrame: 24 months
measure: Complete or partial remission
timeFrame: 24 months
measure: Relapse
timeFrame: 24 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital, Hong Kong
city: Hong Kong
country: Hong Kong
facility: United Christian Hospital
Study officials:
References: