Clinical trial NCT03650400: Pharmacokinetics, Safety and Tolerability of Fevipiprant Delivered Via a Once Daily Chewable Tablet in Children Aged 6 to < 12 Years With Asthma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Asthma
Keywords: Fevipiprant,
GINA 2018,
Pediatrics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-08-28
Enrollment: 11
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
measure: Pharmacokinetics of Fevipiprant by Maximum Plasma Concentration at Steady State (Cmax,ss), After at Least Four Consecutive Days of Dosing
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
measure: Pharmacokinetics of Fevipiprant by Oral Clearance at Steady State (CL/F), After at Least Four Consecutive Days of Dosing
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Secondary outcomes:
measure: Pharmacokinetics of Fevipiprant by CL/F
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours.
measure: Pharmacokinetics of Fevipiprant by Tmax,ss
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
measure: Urinary Excretion of Fevipiprant
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours.
measure: Pharmacokinetics of Fevipiprant by Cmin,ss
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
measure: Pharmacokinetics of the Metabolite CCN362 by AUC0-24h,ss
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
measure: Pharmacokinetics of the Metabolite CCN362 by Cmax,ss
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
measure: Pharmacokinetics of the Metabolite CCN362 by Cmin,ss
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
measure: Pharmacokinetics of the Metabolite CCN362 by Tmax,ss
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
measure: Urinary Excretion of the Metabolite, CCN362
timeFrame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours.
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Columbia
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Tulsa
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Boerne
country: United States
facility: Novartis Investigative Site
state: Texas
city: El Paso
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: