The purpose of this study is to investigate the potential for co-administration of strong inhibitors or inducers of CYP3A4 to alter the pharmacokinetics of fedovapagon.
Fedovapagon is a vasopressin V2 receptor agonist in development for the treatment of nocturia. Agonism of the V2 receptor, located in the collecting ducts of the kidney, leads to translocation of aquaporin channels and increased re absorption of water and anti-diuresis. A number of drugs that are commonly co-prescribed in the population who may present for treatment of nocturia are inhibitors of CYP3A4, including diltiazem, verapamil, erythromycin and clarithromycin and may therefore impact the plasma levels of fedovapagon if co administered. Conversely, concomitant intake of drugs that are potent CYP3A4 inducers may lead to lower than anticipated plasma concentrations of fedovapagon thus reducing the efficacy of fedovapagon. It is therefore important to assess the effect of CYP3A4 induction on the pharmacokinetic (PK) parameters of fedovapagon. The study design uses itraconazole as a potent inhibitor of CYP3A4 and, in a separate cohort of subjects, rifampicin as a potent CYP3A4 inducer at doses intended to maximize the potential to demonstrate an interaction.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
29
PAREXEL Early Phase Clinical Unit Berlin
Berlin, Germany
Plasma fedovapagon concentration in presence and absence of co-administered itraconazole or rifampicin
Time frame: 10-12 days
Maximum observed plasma concentration (Cmax)
Time frame: 10-12 days
Area under the plasma concentration curve versus time curve with extrapolation to infinity (AUC(0-infinity))
Time frame: 10-12 days
Number and type of adverse events
Time frame: 12-14 days
Change from baseline in 12-lead ECG
Time frame: 12-14 days
Change from baseline in vital signs and physical examination
Time frame: 12-14 days
Change from baseline in laboratory assessments
Time frame: 12-14 days
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