Pharmacokinetics and Safety of Fevipiprant in Patients With Renal Impairment Compared to Matched Healthy Subjects

Novartis

Status and phase: Completed; Phase 1

Conditions: Renal Insufficiency

Treatments: Drug: QAW39A2107; Drug: QAW39A; Drug: QAW039

Study type: Interventional

Funder types: Industry

Identifiers

NCT03087942

CQAW039A2107

2016-004218-81 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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

Enrollment: 45 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 4 patient groups

Group 1

Experimental group

Description:

ESRD patients

Treatment:

Drug: QAW039

Group 2

Experimental group

Description:

healthy volunteers

Treatment:

Drug: QAW39A

Group 3

Experimental group

Description:

severe and moderate renal impaired patients

Treatment:

Drug: QAW39A2107

Drug: QAW39A2107

Group 4

Experimental group

Description:

mild renal impaired patients

Treatment:

Drug: QAW39A2107

Drug: QAW39A2107