Asthma
Conditions
Keywords
Fevipiprant,, GINA 2018,, Pediatrics
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).
Interventions
DRUGFevipiprant
Chewable tablet
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Area under the curve (AUC0-24h,ss), steady state following drug administration |
| Pharmacokinetics of Fevipiprant by Maximum Plasma Concentration at Steady State (Cmax,ss), After at Least Four Consecutive Days of Dosing | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Maximum plasma concentration (Cmax,ss) steady state following drug administration. |
| Pharmacokinetics of Fevipiprant by Oral Clearance at Steady State (CL/F), After at Least Four Consecutive Days of Dosing | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Oral clearance (CL/F), steady state following drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Excretion of Fevipiprant | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours. | CLr, amount and fraction of dose excreted over the PK collection interval at steady state, of fevipiprant |
| Pharmacokinetics of Fevipiprant by Cmin,ss | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Pharmacokinetics of fevipiprant by minimum plasma concentration (Cmin,ss) at steady state |
| Pharmacokinetics of the Metabolite CCN362 by AUC0-24h,ss | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Pharmacokinetics of CCN362 metabolite of fevipiprant , area under the curve (AUC0-24h,ss) at steady state. |
| Urinary Excretion of the Metabolite, CCN362 | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours. | CLr, amount and fraction of dose excreted over the PK collection interval at steady state, of the metabolite, CCN362 |
| Pharmacokinetics of the Metabolite CCN362 by Cmin,ss | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Pharmacokinetics of CCN362 metabolite of fevipiprant by minimum plasma concentration (Cmin,ss) at steady state |
| Pharmacokinetics of the Metabolite CCN362 by Tmax,ss | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Pharmacokinetics of CCN362 metabolite of fevipiprant by time of maximum plasma concentration (Tmax,ss) at steady state |
| Pharmacokinetics of the Metabolite CCN362 by Cmax,ss | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Pharmacokinetics of CCN362 metabolite of fevipiprant by maximum plasma concentration (Cmax,ss) at steady state |
| Pharmacokinetics of Fevipiprant by CL/F | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours. | Pharmacokinetics of fevipiprant by oral clearance (CL/F) at steady state |
| Pharmacokinetics of Fevipiprant by Tmax,ss | End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours) | Pharmacokinetics of fevipiprant by time of maximum plasma concentration (Tmax,ss) at steady state |
Countries
United States
Participant flow
Recruitment details
Six US centers recruited 11 subjects in the study.
Pre-assignment details
A total of 19 subjects were screened to enroll 11 subjects in the study
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Fevipiprant 75 mg QAW039 75 mg Chewable tablet | 6 |
| Cohort B Feviprant 375 mg QAW039 375 mg Chewable tablet | 5 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study terminated by sponsor | 0 | 5 |
Baseline characteristics
| Characteristic | Cohort B Feviprant 375 mg | Total | Cohort A Fevipiprant 75 mg |
|---|---|---|---|
| Age, Continuous | 9.4 years STANDARD_DEVIATION 1.52 | 8.7 years STANDARD_DEVIATION 1.74 | 8.2 years STANDARD_DEVIATION 1.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 10 Participants | 6 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 0 / 6 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 5 |
Outcome results
Primary
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
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | 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 | 2380 h*ng/mL | Standard Deviation 1880 |
Primary
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.
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of Fevipiprant by Maximum Plasma Concentration at Steady State (Cmax,ss), After at Least Four Consecutive Days of Dosing | 394 ng/mL | Standard Deviation 286 |
Primary
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.
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of Fevipiprant by Oral Clearance at Steady State (CL/F), After at Least Four Consecutive Days of Dosing | 48.2 L/h | Standard Deviation 32 |
Secondary
Pharmacokinetics of Fevipiprant by CL/F
Pharmacokinetics of fevipiprant by oral clearance (CL/F) at steady state
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours.
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of Fevipiprant by CL/F | 48.2 L/h | Standard Deviation 32 |
Secondary
Pharmacokinetics of Fevipiprant by Cmin,ss
Pharmacokinetics of fevipiprant by minimum plasma concentration (Cmin,ss) at steady state
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of Fevipiprant by Cmin,ss | 28.3 ng/mL | Standard Deviation 13.8 |
Secondary
Pharmacokinetics of Fevipiprant by Tmax,ss
Pharmacokinetics of fevipiprant by time of maximum plasma concentration (Tmax,ss) at steady state
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of Fevipiprant by Tmax,ss | 1.42 h | Standard Deviation 0.916 |
Secondary
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.
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of the Metabolite CCN362 by AUC0-24h,ss | 2760 h*ng/mL | Standard Deviation 1210 |
Secondary
Pharmacokinetics of the Metabolite CCN362 by Cmax,ss
Pharmacokinetics of CCN362 metabolite of fevipiprant by maximum plasma concentration (Cmax,ss) at steady state
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of the Metabolite CCN362 by Cmax,ss | 302 ng/mL | Standard Deviation 134 |
Secondary
Pharmacokinetics of the Metabolite CCN362 by Cmin,ss
Pharmacokinetics of CCN362 metabolite of fevipiprant by minimum plasma concentration (Cmin,ss) at steady state
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of the Metabolite CCN362 by Cmin,ss | 33.6 ng/mL | Standard Deviation 22.6 |
Secondary
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
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours)
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Pharmacokinetics of the Metabolite CCN362 by Tmax,ss | 2.69 h | Standard Deviation 1.2 |
Secondary
Urinary Excretion of Fevipiprant
CLr, amount and fraction of dose excreted over the PK collection interval at steady state, of fevipiprant
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours.
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Urinary Excretion of Fevipiprant | 6.61 L/h | Standard Deviation 4.88 |
Secondary
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
Time frame: End of Treatment (pre-dose, 0.5hours, 1 hour, 2 hours, 3 hours, 5 hours and 8 hours.
Population: All treated participants with a valid PK measurement. No PK samples were collected for PK analysis in Cohort B due to early study termination.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A Fevipiprant 75 mg | Urinary Excretion of the Metabolite, CCN362 | 5.10 L/h | Standard Deviation 1.96 |