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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02440841
Recruitment Status : Completed
First Posted : May 12, 2015
Last Update Posted : July 30, 2015
Information provided by (Responsible Party):
Vantia Ltd

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.

Condition or disease Intervention/treatment Phase
Nocturia Drug: fedovapagon Drug: Itraconazole Drug: rifampicin Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2015
Actual Primary Completion Date : July 2015
Actual Study Completion Date : July 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: fedovapagon and itraconazole
Two daily doses of fedovapagon and once daily doses of itraconazole
Drug: fedovapagon
Drug: Itraconazole
Experimental: fedovapagon and rifampicin
Two daily doses of fedovapagon and once daily doses of rifampicin
Drug: fedovapagon
Drug: rifampicin

Primary Outcome Measures :
  1. Plasma fedovapagon concentration in presence and absence of co-administered itraconazole or rifampicin [ Time Frame: 10-12 days ]

Secondary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) [ Time Frame: 10-12 days ]
  2. Area under the plasma concentration curve versus time curve with extrapolation to infinity (AUC(0-infinity)) [ Time Frame: 10-12 days ]
  3. Number and type of adverse events [ Time Frame: 12-14 days ]
  4. Change from baseline in 12-lead ECG [ Time Frame: 12-14 days ]
  5. Change from baseline in vital signs and physical examination [ Time Frame: 12-14 days ]
  6. Change from baseline in laboratory assessments [ Time Frame: 12-14 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes

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®

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02440841

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PAREXEL Early Phase Clinical Unit Berlin
Berlin, Germany, 14050
Sponsors and Collaborators
Vantia Ltd
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Study Director: Tshibuabua Kabasela Parexel

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Responsible Party: Vantia Ltd Identifier: NCT02440841     History of Changes
Other Study ID Numbers: 483-010
First Posted: May 12, 2015    Key Record Dates
Last Update Posted: July 30, 2015
Last Verified: July 2015
Keywords provided by Vantia Ltd:
drug-drug interaction
Additional relevant MeSH terms:
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Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers