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

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.
 
ClinicalTrials.gov Identifier: NCT03087942
Recruitment Status : Completed
First Posted : March 23, 2017
Last Update Posted : October 11, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.


Condition or disease Intervention/treatment Phase
Renal Insufficiency Drug: QAW039 Drug: QAW39A Drug: QAW39A2107 Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 5, 2017
Actual Primary Completion Date : August 7, 2018
Actual Study Completion Date : August 7, 2018

Arm Intervention/treatment
Experimental: Group 1
ESRD patients
Drug: QAW039
450 mg
Other Name: fevipiprant

Experimental: Group 2
healthy volunteers
Drug: QAW39A
450 mg
Other Name: fevipiprant

Experimental: Group 3
severe and moderate renal impaired patients
Drug: QAW39A2107
450 mg
Other Name: fevipiprant

Experimental: Group 4
mild renal impaired patients
Drug: QAW39A2107
450 mg
Other Name: fevipiprant




Primary Outcome Measures :
  1. Pharmacokinetics: Plasma concentration of fevipiprant by AUClast [ Time Frame: 68 hours post dose ]
    AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration

  2. Pharmacokinetics: Plasma concentration of fevipiprant by AUCinf [ Time Frame: 68 hours post dose ]
    AUCinf is the area under the plasma concentration-time curve from time zero to infinity

  3. Pharmacokinetics: Plasma concentration of fevipiprant by Cmax [ Time Frame: 68 hours post dose ]
    Cmax is the observed maximum plasma concentration following drug administration

  4. Pharmacokinetics: Plasma contentration of fevipiprant by AUC0-68h [ Time Frame: 68 hours post dose ]
    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


Secondary Outcome Measures :
  1. Relationship between plasma pharmacokinetics of fevipiprant by AUClast and between eGFR as well as creatinine clearance [ Time Frame: 68 hours post dose ]
    AUClast (the area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration ) related to eGFR estimated by the Modification of Diet in Renal Disease (MDRD) formula, and Cockcroft-Gault (C-G) estimated creatinine clearance

  2. Relationship between plasma pharmacokinetics of fevipiprant by AUCinf and between eGFR as well as creatinine clearance [ Time Frame: 68 hours post dose ]
    AUCinf (the area under the plasma concentration time curve from time zero to infinity) related to eGFR estimated by the Modification of Diet in Renal Disease (MDRD) formula, and Cockcroft-Gault (C-G) estimated creatinine clearance

  3. Relationship between plasma pharmacokinetics of fevipiprant by Cmax and between eGFR as well as creatinine clearance [ Time Frame: 68 hours post dose ]
    Cmax (observed maximum plasma concentration following drug administration) related to eGFR estimated by the Modification of Diet in Renal Disease (MDRD) formula, and Cockcroft-Gault (C-G) estimated creatinine clearance

  4. Pharmacokinetics of the metabolite CCN362 by AUClast [ Time Frame: 68 hours post dose ]
    AUClast is the area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration

  5. Pharmacokinetics of the metabolite CCN362 by AUCinf [ Time Frame: 68 hours post dose ]
    AUCinf is the area under the plasma concentration time curve from time zero to infinity

  6. Pharmacokinetics of the metabolite CCN362 by Cmax [ Time Frame: 68 hours post dose ]
    Cmax is the observed maximum plasma concentration following drug administration

  7. Pharmacokinetics: plasma concentration of fevipiprant in patients with End Stage Renal Disease (ESRD) [ Time Frame: 68 hours post dose ]
    Partial AUCs (AUCt1-t2) covering the time interval of dialysis, Cmax and total AUCs (AUC0-68h and/or AUCinf) will be compared

  8. urinary excretion of fevipiprant and metabolite in patients with renal impairment compared to healthy controls [ Time Frame: 24 hours post dose ]
    Renal clearance (CLr) and fraction of dose excreted in urine for fevipiprant and metabolite



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)

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 ClinicalTrials.gov identifier (NCT number): NCT03087942


Locations
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United States, Florida
Novartis Investigative Site
Orlando, Florida, United States, 32809
Germany
Novartis Investigative Site
Grunstadt, Germany, 67269
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03087942    
Other Study ID Numbers: CQAW039A2107
2016-004218-81 ( EudraCT Number )
First Posted: March 23, 2017    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
end stage renal disase ESRD
dialysis effect on pharmacokinetics PK
renal impairment
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases
Indoleacetic Acids
Plant Growth Regulators
Growth Substances
Physiological Effects of Drugs