Clinical trial NCT03087942: Pharmacokinetics and Safety of Fevipiprant in Patients With Renal Impairment Compared to Matched Healthy Subjects
Official title: An Open-label, Single-dose, Parallel Group Study to Assess the Pharmacokinetics of Fevipiprant (QAW039) in Patients With End-stage Renal Disease on Hemodialysis and Optionally in Patients With Severe to Moderate and Mild Renal Impairment Compared to Matched Healthy Volunteers Including a Cross-over Assessment in End-stage Renal Disease Patients on the Effect of Dialysis on Fevipiprant Pharmacokinetics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Insufficiency
Keywords: end stage renal disase ESRD
dialysis effect on pharmacokinetics PK
renal impairment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-03-23
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to assess whether renal impairment could affect fevipiprant pharmacokinetics (PK) to the extent that dosage adjustment is appropriate for this patient population.

The study also aims to determine the effect of dialysis on the fevipiprant pharmacokinetic profile as the procedure might remove a significant fraction of the drug.

Detailed description: The purpose of this study is to determine if the pharmacokinetic profile of fevipiprant is different in patients with renal impariment compared to healthy matched volunteers to an extent that would require an adjustment of the dosage. Data from this study will be used to guide enrollment criteria in future clinical trials and to support regulatory submission and labeling information

Eligibility criteria: Inclusion Criteria:

* Healthy subjects must satisfy the criteria for normal renal function as evidenced by normal Glomerular Filtration Rate (GFR): eGFR ≥ 90 mL/min/1.73m2; each healthy subject must match in age (+/- 10years), gender, smoking status, and weight (+/- 15%), a patient from the renail impaired patient groups:
* A body mass index (BMI) within the range of 18 - 36 kg/m2
* ESRD patients on hemodialysis: an glomerulo filtration rat GFR of \< 15 mL/min/1.73 m2
* patients with severe renal impairment: GFR of\< 30 mL/min/1.73m2 (without need of hemodialysis);
* patients with moderate renal impairment: 30 mL/min/1.73m2 ≤ eGFR \< 60 mL/min/1.73m2;
* patients with mild impairment: 60 mL/min/1.73m2 ≤ eGFR \< 90 mL/min/1.73m2

Exclusion Criteria:

* Pregnant or nursing (lactating) women
* History or evidence of any inherited bilirubin disease or disorder
* subjects participating in another study
* malignancies in the past
* Hemoglobin levels below 10 g/dL at screening
* HIV positiv
* Heavy smokers (≥20 cigarettes per day)
* Liver disease, as indicated by ALT, γ-GT, AST and alkaline phosphatase which should not exceed twice the upper limit of normal and should be stable (e.g. increased liver values known from previous patient records). Serum bilirubin \> 27 μmol/L (1.6 mg/dL)
* Clinically significant ECG changes and/or arrhythmias
* Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV)

Primary outcomes:
measure: Pharmacokinetics: Plasma concentration of fevipiprant by AUClast
timeFrame: 68 hours post dose
measure: Pharmacokinetics: Plasma concentration of fevipiprant by AUCinf
timeFrame: 68 hours post dose
measure: Pharmacokinetics: Plasma concentration of fevipiprant by Cmax
timeFrame: 68 hours post dose
measure: Pharmacokinetics: Plasma contentration of fevipiprant by AUC0-68h
timeFrame: 68 hours post dose
Secondary outcomes:
measure: Relationship between plasma pharmacokinetics of fevipiprant by AUClast and between eGFR as well as creatinine clearance
timeFrame: 68 hours post dose
measure: Relationship between plasma pharmacokinetics of fevipiprant by AUCinf and between eGFR as well as creatinine clearance
timeFrame: 68 hours post dose
measure: Relationship between plasma pharmacokinetics of fevipiprant by Cmax and between eGFR as well as creatinine clearance
timeFrame: 68 hours post dose
measure: Pharmacokinetics of the metabolite CCN362 by AUClast
timeFrame: 68 hours post dose
measure: Pharmacokinetics of the metabolite CCN362 by AUCinf
timeFrame: 68 hours post dose
measure: Pharmacokinetics of the metabolite CCN362 by Cmax
timeFrame: 68 hours post dose
measure: Pharmacokinetics: plasma concentration of fevipiprant in patients with End Stage Renal Disease (ESRD)
timeFrame: 68 hours post dose
measure: urinary excretion of fevipiprant and metabolite in patients with renal impairment compared to healthy controls
timeFrame: 24 hours post dose
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Grunstadt
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: