Study in Healthy Male Subjects to Evaluate the Effect of Itraconazole and Rifampicin on the PK of Fedovapagon
Study in Healthy Male Subjects to Evaluate the Effect of Itraconazole and Rifampicin on the PK of Fedovapagon
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.
Inclusion Criteria:

 -  Healthy males aged 18 to 45

 -  Have a body mass index between 18 and 29.9 kg/m2 (weight: ≥50 kg and ≤100 kg)

 -  No clinically significant medical history

 -  Ability to comply with the requirements of the study

 -  Provide written informed consent

 -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) should be below or
 equal to upper level of normal (ULN). Otherwise liver enzymes should show no clinical
 significant abnormalities. Total bilirubin should not exceed 1.5 x ULN. Liver enzymes
 will be re-tested only once before randomization if required.

 -  Be judged by the Investigator to be in good health based on medical history (in
 particular, no congestive heart failure, ischemic heart disease, valvular heart
 disease, significant pulmonary disease, renal failure, edematous disorder, liver
 disease, gastric disorders, porphyria, diabetes mellitus or hereditary disorders of
 carbohydrate metabolism), physical examination, vital sign measurements and laboratory
 safety tests

 -  Agree to refrain from the consumption of grapefruit or grapefruit juice, apple or
 orange juice, vegetables from the mustard green family (e.g., kale, broccoli,
 watercress, collard greens, kohlrabi, brussels sprouts, mustard) and charbroiled meats
 containing products beginning 1 week prior to administration of the initial
 administration of trial drug, throughout the trial

 -  Use of any prescribed medication or St John's Wort within 14 days (or 5 half-lives if
 this is longer) or over-the-counter medication (except paracetamol) within 1 week of
 dosing. Specific medication not to be taken within 2 weeks of (before or after)
 administration of itraconazole is described in the Summary of Product Characteristic
 for Sempera®