Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03852888 |
| Other study ID # |
PO18172* |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
November 14, 2018 |
| Est. completion date |
November 25, 2021 |
Study information
| Verified date |
December 2021 |
| Source |
CHU de Reims |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Methotrexate is a key treatment for inflammatory rheumatism. Therapeutic compliance with
methotrexate is difficult to measure because of a lack of objective testing; however,
therapeutic compliance is essential for the proper management of a patient.
The objective is to characterize the kinetics of elimination of methotrexate and its main
metabolite7-OH-methotrexate for observant patients according to treatment (dosage,
administration) and patient characteristics.
Once this kinetics is characterized, it will be considered as a comparison reference to
identify non-observant patients that is to say having concentrations lower than the lower
bound of the confidence interval of the observed concentrations.
Description:
Type of study: prospective longitudinal descriptive observational study Population: Patients
treated for rheumatoid arthritis in the Rheumatology Department of Reims University Hospital
and treated with methotrexate monotherapy (weekly intake).
Assessment Criteria: Urinary concentration of methotrexate and its metabolite
7-OH-methotrexate at different days post-administration.
Investigation plan: Determination of urinary methotrexate and its 7-OH-methotrexate
metabolite on 8 urine samples (just before taking, then 2 hours after treatment and then on
D3, D4, D5, D6, D7, D8 before re-taking methotrexate) in the same patient treated with
methotrexate weekly. It will take 10 patients per dosage level, followed by 3 to 8 days
post-administration, to distinguish the urinary methotrexate concentrations of observant
patients from those of non-observant patients with the power of 90%.
Statistical Analysis Plan: The main objective of this study is to characterize the
elimination kinetics of methotrexate and its major metabolite 7-OH-methotrexate in patients
observing the various methotrexate regimens. Once this kinetics is characterized, it will be
considered as a comparison reference to identify non-observant patients that is to say having
concentrations lower than the lower bound of the confidence interval of the observed
concentrations.
On the one hand, simulations based on published population pharmacokinetic models of plasma
methotrexate are used to estimate the periods of elimination of methotrexate. The simulations
that the investigators carried out on the basis of these models highlight that these
elimination periods are between 3 and at the latest 9.5 days. These periods correspond to the
time required to eliminate 99% of methotrexate.
Finally, it will take 10 patients per dosage level, by administration (oral or subcutaneous),
followed by the 3rd to 8th day post-administration, to distinguish urinary methotrexate
concentrations from observant patients (1 +/- 0.3 nM) of non-observant patients (0.4 +/- 0.4
nM) with the power of 90%. The dosage schedules are 10, 15, 20 mg methotrexate / week per-os
or subcutaneous injection. It will recruit 60 patients. The follow-up will be limited to 8
days maximum because the administration is done once a week.
