Pharmacokinetics, Safety and Tolerability of Fevipiprant Delivered Via a Once Daily Chewable Tablet in Children Aged 6 to < 12 Years With Asthma

Study Overview
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Brief Summary
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The purpose of this study was to assess the pharmacokinetics (PK) of fevipiprant (QAW039) delivered as a chewable tablet (CT) in pediatric asthma subjects aged 6 to < 12 years with asthma. The results of this study will support the identification of a fevipiprant dose for subsequent pediatric efficacy studies aiming to provide an exposure similar to that of the to-be marketed adult/adolescent dose. In addition, the first data on safety and tolerability of fevipiprant in this age group was obtained.

Detailed Description
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The purpose of this study was to assess the pharmacokinetics (PK) of fevipiprant delivered as a chewable tablet (CT) in pediatric asthma subjects aged 6 to < 12 years. The results of this study would have supported the identification of a fevipiprant dose for subsequent pediatric efficacy studies aiming to provide an exposure similar to that of the to-be marketed adult/adolescent dose. Based on evaluation of the fevipiprant asthma development program in the recently completed studies (CQAW039A2307/ CQAW039A2314) in the adult population (the analyses of these studies did not meet the clinically relevant threshold for reduction in rate of moderate-to-severe exacerbation compared to placebo over a 52-week treatment period for either of the doses [i.e. 150 mg/ 450 mg]), Novartis decided to discontinue this study (CQAW039B2201).

Official Title
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A Multicenter, Open-label, 8 Day Treatment Study to Assess the Pharmacokinetics, Safety and Tolerability of Fevipiprant Delivered Via a Once Daily Chewable Tablet in Children Aged 6 to <12 Years With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fevipiprant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children Written informed consent by parent(s)/legal guardian(s) for the pediatric patient and assent by the pediatric patient (depending on local requirements) must be obtained before any study-specific assessment is performed. Confirmed/documented diagnosis of asthma, as defined by national or international asthma guidelines for at least 6 months prior to study enrollment. Subjects using asthma rescue medication (e.g. SABA) without asthma controller therapy or patients receiving daily treatment with a stable dose ICS (with or without additional controller such as long-acting β-agonists (LABA), long-acting muscarinic antagonists (LAMA)) for at least 4 weeks prior to Treatment Visit (Day 1). Subjects must be able to attend study visits as per Study Visit Assessment Schedule (Section 8) which includes 8 to 9 hours in the clinic/home on the day of End of Treatment Visit and have blood draws as scheduled in the study. Exclusion Criteria: Use of other investigational drugs within 5 half-lives of enrollment, or (within 30 days (for small molecules)/until the expected pharmacodynamic effect has returned to baseline (for biologics)), whichever is longer. Subject is unable to ingest banana and/or yogurt History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes. History of chronic lung disease other than asthma such as and not limited to, sarcoidosis interstitial lung disease, cystic fibrosis, mycobacterial or other infection (including active tuberculosis or atypical mycobacterial disease). History of active bacterial, viral or fungal infection within 6 weeks of Treatment Visit (Day 1).

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: There will be 2 treatment dose cohorts studied (fevipiprant dose A once daily and one higher dose selected based on PK obtained at dose A mg/day, fevipiprant dose B once daily). Within each dose cohort, subjects will be stratified approximately 1:1 ratio into 2 age groups: ages 6 to < 9 years and ages 9 to < 12 years.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A Fevipiprant 75 mg<br>QAW039 75 mg Chewable tablet | Drug: Fevipiprant<br>* Chewable tablet<br>* Other names: QAW039;|
| Experimental: Cohort B Feviprant 375 mg<br>QAW039 375 mg Chewable tablet | Drug: Fevipiprant<br>* Chewable tablet<br>* Other names: QAW039;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Fevipiprant by Area Under the Curve From 0 to 24 Hours at Steady State (AUC0-24h,ss), After at Least Four Consecutive Days of Dosing | Area under the curve (AUC0-24h,ss), steady state following drug administration | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 
| Pharmacokinetics of Fevipiprant by Maximum Plasma Concentration at Steady State (Cmax,ss), After at Least Four Consecutive Days of Dosing | Maximum plasma concentration (Cmax,ss) steady state following drug administration. | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 
| Pharmacokinetics of Fevipiprant by Oral Clearance at Steady State (CL/F), After at Least Four Consecutive Days of Dosing | Oral clearance (CL/F), steady state following drug administration. | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Fevipiprant by CL/F | Pharmacokinetics of fevipiprant by oral clearance (CL/F) at steady state | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours. | 
| Pharmacokinetics of Fevipiprant by Tmax,ss | Pharmacokinetics of fevipiprant by time of maximum plasma concentration (Tmax,ss) at steady state | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 
| Urinary Excretion of Fevipiprant | CLr, amount and fraction of dose excreted over the PK collection interval at steady state, of fevipiprant | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours. | 
| Pharmacokinetics of Fevipiprant by Cmin,ss | Pharmacokinetics of fevipiprant by minimum plasma concentration (Cmin,ss) at steady state | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 
| Pharmacokinetics of the Metabolite CCN362 by AUC0-24h,ss | Pharmacokinetics of CCN362 metabolite of fevipiprant , area under the curve (AUC0-24h,ss) at steady state. | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 
| Pharmacokinetics of the Metabolite CCN362 by Cmax,ss | Pharmacokinetics of CCN362 metabolite of fevipiprant by maximum plasma concentration (Cmax,ss) at steady state | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 
| Pharmacokinetics of the Metabolite CCN362 by Cmin,ss | Pharmacokinetics of CCN362 metabolite of fevipiprant by minimum plasma concentration (Cmin,ss) at steady state | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 
| Pharmacokinetics of the Metabolite CCN362 by Tmax,ss | Pharmacokinetics of CCN362 metabolite of fevipiprant by time of maximum plasma concentration (Tmax,ss) at steady state | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | 
| Urinary Excretion of the Metabolite, CCN362 | CLr, amount and fraction of dose excreted over the PK collection interval at steady state, of the metabolite, CCN362 | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fevipiprant,, GINA 2018,, Pediatrics