PRACTICAL study: Pharmaco-enhancement in Rheumatoid Arthritis with Cobicistat to dose Tofacitinib In Clinic Adequately Low. A within-subject sequential study.
- Conditions
- chronic inflammation of the jointspsoriatic arthritisRheumatoid arthritis1000381610023213
- Registration Number
- NL-OMON48994
- Lead Sponsor
- Radboud Universitair Medisch Centrum
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
* Rheumatoid arthritis (either 2010 ACR RA and/or 1987 RA criteria and/or
clinical diagnosis of the treating rheumatologist, fulfilled at any time point
between start of the disease and inclusion) or Psoriatic arthritis (either
Classification Criteria for Psoriatic Arthritis (CASPAR) and/or diagnosed with
peripheral SpA of the psoriatic arthritis subtype by a rheumatologist)
* Patients using tofacitinib for * 2 weeks in the standard dose of 5mg BID.
* Patient informed consent, *18 years old and mentally competent
* Ability to measure the outcome of the study in this patient (e.g. patient
availability; willing and being able to undergo repeated serum samples)
* Ability to read and communicate well in Dutch
* Concomitant use of inducers or potent inhibitors of CYP3A4 or moderate
inhibitors of CYP3A4 and potent inhibitors of CYP2C19, or medication sensitive
to changes in metabolism as a result of cobicistat co-treatment, as assessed
with the KNMP *G-standaard* unless an alternative is listed in Table 1.
* Known contra-indications for treatment with cobicistat in line with the
summary of product characteristics
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To investigate the bioequivalence of tofacitinib 5mg and cobicistat 150 mg QD<br /><br>(intervention) compared to tofacitinib 5mg BID alone (control) with regard to<br /><br>the relevant steady state pharmacokinetic parameters (average concentration at<br /><br>steady state (Cavg,ss )/Area Under the Curve (AUC0-24), as defined by a 90%<br /><br>confidence interval of the geometric mean ratio falling entirely between 75%<br /><br>and 125%.</p><br>
- Secondary Outcome Measures
Name Time Method <p>* To construct a mechanistic population pharmacokinetic model describing the<br /><br>quantitative effect of cobicistat on tofacitinib pharmacokinetics;<br /><br>* To describe the relevant pharmacokinetic parameters (Cavg,ss, AUC0-24,<br /><br>Cmax,ss, tmax,ss, Ctrough and t1/2) after administration of tofacitinib 5mg and<br /><br>cobicistat 150 mg QD compared to tofacitinib 5mg BID alone;<br /><br>* To evaluate the safety and tolerability of tofacitinib 5mg and cobicistat 150<br /><br>mg QD compared to tofacitinib 5mg BID alone;<br /><br>* To provide a suitable dosing scheme of tofacitinib and cobicistat for a<br /><br>future clinical non-inferiority study, based on the developed pharmacokinetic<br /><br>model, in case tofacitinib 5mg and cobicistat 150 mg QD is not equivalent to<br /><br>tofacitinib 5mg BID alone in this study;<br /><br>* To evaluate the efficacy of both regimes by DAS28-CRP;<br /><br>* To establish which regimen is preferred by patients based on medication QD or<br /><br>BID. </p><br>