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Pharmacokinetics of Fevipiprant (QAW039) in Patients With Hepatic Impairment Compared to Matched Healthy Subjects

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03048448
Collaborator
(none)
42
Enrollment
2
Locations
1
Arm
22.7
Actual Duration (Months)
21
Patients Per Site
0.9
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will characterize the pharmacokinetics (PK) of QAW039 after a single oral dose of QAW039 in patients with hepatic impairment compared to healthy matched control subjects.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

The purpose of this study is to determine if the pharmacokinetic profile of Fevipiprant is different in patients with hepatic impairment 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
An Open-label, Single-dose, Parallel-group Study to Assess the Pharmacokinetics of Fevipiprant (QAW039) in Patients With Hepatic Impairment Compared to Matched Healthy Subjects
Actual Study Start Date :
May 31, 2017
Actual Primary Completion Date :
Apr 22, 2019
Actual Study Completion Date :
Apr 22, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Fevipiprant 450mg

450mg Film Coated Tablet

Drug: Fevipiprant
Single 450mg dose
Other Names:
  • QAW039

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Pharmacokinetics: Plasma concentration of Fevipiprant by AUClast [120 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 [120 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 [120 hours post-dose]

      Cmax is the observed maximum plasma concentration following drug administration

    Secondary Outcome Measures

    1. Relationship between plasma pharmacokinetics of Fevipiprant by AUClast and baseline hepatic function. [120 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 Child Pugh score

    2. Relationship between plasma pharmacokinetics of Fevipiprant by AUCinf and baseline hepatic function. [120 hours post-dose]

      AUCinf (the area under the plasma concentration-time curve from time zero to infinity) related to Child Pugh score

    3. Relationship between plasma pharmacokinetics of Fevipiprant by Cmax and baseline hepatic function. [120 hours post-dose]

      Cmax is the observed maximum plasma concentration following drug administration related to Child Pugh score

    4. Pharmacokinetics of the metabolite CCN362 by AUClast [120 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 [120 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 [120 hours post-dose]

      Cmax is the observed maximum plasma concentration following drug administration

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    All subjects

    • Weight of at least 50 kg and no more than 120 kg and have a body mass index in the range 18.0-36.0 kg/m2

    Patients with hepatic impairment

    • Moderate hepatic impairment (Group 1): Child-Pugh Class B (7-9 points),

    • Severe hepatic impairment (Group 2): Child-Pugh Class C (10-15 points

    • Mild hepatic impairment (Group 4): Child-Pugh Class A (5-6 points)

    Healthy subjects

    • Match in age (±5 years), gender, smoking status, and weight (± 15%) to an individual patient.

    • In good health as determined by past medical history, physical examination, electrocardiogram, laboratory tests and urinalysis at screening.

    Exclusion Criteria:

    All subjects

    • History of hypersensitivity and/or idiosyncracies to QAW039 or to drugs of similar classes (CRTh2 antagonists).

    • Use of co-medications that may impact QAW039 exposure such as broad range UGT inhibitors or strong inhibitors of OAT3, OATP1B3, and P-gp, including but not limited to probenecid, ritonavir, valproic acid, and rifampin

    • Surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.

    • History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

    • Pregnant or nursing (lactating) women.

    • Women of child-bearing potential

    Patients with hepatic impairment

    • Hepatic impairment due to non-liver disease (e.g., right heart failure)

    • Current symptoms or history of encephalopathy Grade III or IV within the past 6 months

    • Primary biliary liver cirrhosis and biliary obstruction

    • Emergency room visit or hospitalization due to liver disease within the preceding 3 months.

    • Severe complications of liver disease within the preceding 3 months.

    Healthy subjects

    • Liver disease or liver injury as indicated by abnormal liver function tests.

    • Any single parameter of ALT, AST, γ-GT, alkaline phosphatase or serum bilirubin must not exceed 1.5 x upper limit of normal (ULN)

    • Any elevation above ULN of more than one parameter of ALT, AST, γ GT, alkaline phosphatase or serum bilirubin will exclude a subject from participation in the study

    • A positive Hepatitis B surface antigen or Hepatitis C test result.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigative Site Anaheim California United States 92801
    2 Novartis Investigative Site Orlando Florida United States 32809

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03048448
    Other Study ID Numbers:
    • CQAW039A2108
    First Posted:
    Feb 9, 2017
    Last Update Posted:
    Dec 11, 2020
    Last Verified:
    Apr 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Hepatic impairment,
    Fevipiprant,
    adults,
    pharmacokinetics
    Additional relevant MeSH terms:
    Liver Diseases

    Study Results

    No Results Posted as of Dec 11, 2020