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

Primary Purpose

Nocturia

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

fedovapagon

Itraconazole

rifampicin

About this trial

This is an interventional treatment trial for Nocturia focused on measuring VA106483, fedovapagon, drug-drug interaction, DDI, males, rifampicin, rifampin, itraconazole, CYP3A4, pharmacokinetics, PK

Eligibility Criteria

18 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

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®

Sites / Locations

PAREXEL Early Phase Clinical Unit Berlin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

fedovapagon and itraconazole

fedovapagon and rifampicin

Arm Description

Two daily doses of fedovapagon and once daily doses of itraconazole

Two daily doses of fedovapagon and once daily doses of rifampicin

Outcomes

Primary Outcome Measures

Plasma fedovapagon concentration in presence and absence of co-administered itraconazole or rifampicin

Secondary Outcome Measures

Maximum observed plasma concentration (Cmax)

Area under the plasma concentration curve versus time curve with extrapolation to infinity (AUC(0-infinity))

Number and type of adverse events

Change from baseline in 12-lead ECG

Change from baseline in vital signs and physical examination

Change from baseline in laboratory assessments

Full Information

NCT ID

NCT02440841

First Posted

May 7, 2015

Last Updated

July 29, 2015

Sponsor

Vantia Ltd

1. Study Identification

Unique Protocol Identification Number

NCT02440841

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Completed

Study Start Date

May 2015 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

July 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vantia Ltd

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nocturia

Keywords

VA106483, fedovapagon, drug-drug interaction, DDI, males, rifampicin, rifampin, itraconazole, CYP3A4, pharmacokinetics, PK

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

fedovapagon and itraconazole

Arm Type

Experimental

Arm Description

Two daily doses of fedovapagon and once daily doses of itraconazole

Arm Title

fedovapagon and rifampicin

Arm Type

Experimental

Arm Description

Two daily doses of fedovapagon and once daily doses of rifampicin

Intervention Type

Drug

Intervention Name(s)

fedovapagon

Intervention Type

Drug

Intervention Name(s)

Itraconazole

Intervention Type

Drug

Intervention Name(s)

rifampicin

Primary Outcome Measure Information:

Title

Plasma fedovapagon concentration in presence and absence of co-administered itraconazole or rifampicin

Time Frame

10-12 days

Secondary Outcome Measure Information:

Title

Maximum observed plasma concentration (Cmax)

Time Frame

10-12 days

Title

Area under the plasma concentration curve versus time curve with extrapolation to infinity (AUC(0-infinity))

Time Frame

10-12 days

Title

Number and type of adverse events

Time Frame

12-14 days

Title

Change from baseline in 12-lead ECG

Time Frame

12-14 days

Title

Change from baseline in vital signs and physical examination

Time Frame

12-14 days

Title

Change from baseline in laboratory assessments

Time Frame

12-14 days

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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®

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tshibuabua Kabasela

Organizational Affiliation

Parexel

Official's Role

Study Director

Facility Information:

Facility Name

PAREXEL Early Phase Clinical Unit Berlin

City

Berlin

ZIP/Postal Code

14050

Country

Germany

12. IPD Sharing Statement

Learn more about this trial

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

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