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

Nocturia Clinical Trial

Official title:

Single Center, Open-Label, Single-Sequence, Within-Subject Study In Two Cohorts Of Healthy Male Subjects Comparing Single-Dose Pharmacokinetics Of Fedovapagon Alone And In Combination With A CYP3A4 Inhibitor, Itraconazole, Or A CYP3A4 Inducer, Rifampicin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02440841
• Other study ID #: 483-010
• Status: Completed
• Phase: Phase 1
• First received: May 7, 2015
• Last updated: July 29, 2015
• Start date: May 2015
• Est. completion date: July 2015

Study information

• Verified date: July 2015
• Source: Vantia Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: July 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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®

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Nocturia

Intervention

Drug:
• fedovapagon

• Itraconazole

• rifampicin

Locations

Country	Name	City	State
Germany	PAREXEL Early Phase Clinical Unit Berlin	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Vantia Ltd

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma fedovapagon concentration in presence and absence of co-administered itraconazole or rifampicin		10-12 days	No
Secondary	Maximum observed plasma concentration (Cmax)		10-12 days	No
Secondary	Area under the plasma concentration curve versus time curve with extrapolation to infinity (AUC(0-infinity))		10-12 days	No
Secondary	Number and type of adverse events		12-14 days	No
Secondary	Change from baseline in 12-lead ECG		12-14 days	No
Secondary	Change from baseline in vital signs and physical examination		12-14 days	No
Secondary	Change from baseline in laboratory assessments		12-14 days	No