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

NCT03087942 | Completed Phase 1 FDA Drug

• 2 other identifiers: CQAW039A21072016-004218-81
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 2

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.

Conditions

Renal Insufficiency

Keywords

end stage renal disase ESRD; dialysis effect on pharmacokinetics PK; renal impairment

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics: Plasma concentration of fevipiprant by AUClast

  AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration

  68 hours post dose

• Pharmacokinetics: Plasma concentration of fevipiprant by AUCinf

  AUCinf is the area under the plasma concentration-time curve from time zero to infinity

  68 hours post dose

• Pharmacokinetics: Plasma concentration of fevipiprant by Cmax

  Cmax is the observed maximum plasma concentration following drug administration

  68 hours post dose

• Pharmacokinetics: Plasma contentration of fevipiprant by AUC0-68h

  AUC0-68h is the area under the plasma concentration from time zero to time 68 hours of the last measured concentration above the limit of quantification after dosing

  68 hours post dose

Secondary Outcomes (8)

• Relationship between plasma pharmacokinetics of fevipiprant by AUClast and between eGFR as well as creatinine clearance

  68 hours post dose

• Relationship between plasma pharmacokinetics of fevipiprant by AUCinf and between eGFR as well as creatinine clearance

  68 hours post dose

• Relationship between plasma pharmacokinetics of fevipiprant by Cmax and between eGFR as well as creatinine clearance

  68 hours post dose

• Pharmacokinetics of the metabolite CCN362 by AUClast

  68 hours post dose

• Pharmacokinetics of the metabolite CCN362 by AUCinf

  68 hours post dose

Study Arms (4)

Group 1

EXPERIMENTAL

ESRD patients

Drug: QAW039

Group 2

EXPERIMENTAL

healthy volunteers

Drug: QAW39A

Group 3

EXPERIMENTAL

severe and moderate renal impaired patients

Drug: QAW39A2107

Group 4

EXPERIMENTAL

mild renal impaired patients

Drug: QAW39A2107

Interventions

QAW039 DRUG

450 mg

Also known as: fevipiprant

Group 1

QAW39A DRUG

450 mg

Also known as: fevipiprant

Group 2

QAW39A2107 DRUG

450 mg

Also known as: fevipiprant

Group 3

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Orlando, Florida, 32809, United States

Location

Novartis Investigative Site

Grünstadt, 67269, Germany

Location

Related Links

• Results for CQAW039A2107 can be found on the Novartis Clinical Trial Results Website
• A Plain Language Trial Summary is available on novartisclinicatrials.com

MeSH Terms

Conditions

Renal Insufficiency

Interventions

fevipiprant

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2017
• First Posted: March 23, 2017
• Study Start: July 5, 2017
• Primary Completion: August 7, 2018
• Study Completion: August 7, 2018
• Last Updated: December 11, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); DE (1)