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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03650400
• Collaborator: (none)
• Enrollment: 11
• Locations: 6
• Arms: 2
• Actual Duration (Months): 8.7
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Fevipiprant	Phase 2

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• 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.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)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 1, 2019
• Actual Primary Completion Date: Dec 16, 2019
• Actual Study Completion Date: Jan 22, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A Fevipiprant 75 mg QAW039 75 mg Chewable tablet	Drug: Fevipiprant; Chewable tablet; Other Names: QAW039
Experimental: Cohort B Feviprant 375 mg QAW039 375 mg Chewable tablet	Drug: Fevipiprant; Chewable tablet; Other Names: QAW039

Outcome Measures

Primary Outcome Measures

1. 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

2. 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.

3. 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 Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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.

6. 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

7. 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

8. 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

9. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Minneapolis	Minnesota	United States	55402
2	Novartis Investigative Site	Columbia	Missouri	United States	65203
3	Novartis Investigative Site	Tulsa	Oklahoma	United States	74136
4	Novartis Investigative Site	Boerne	Texas	United States	78006
5	Novartis Investigative Site	El Paso	Texas	United States	79903
6	Novartis Investigative Site	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Feb 13, 2019
• Statistical Analysis Plan - Feb 28, 2020

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03650400
• Other Study ID Numbers: CQAW039B2201
• First Posted: Aug 28, 2018
• Last Update Posted: Oct 11, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Fevipiprant,; GINA 2018,; Pediatrics
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	Six US centers recruited 11 subjects in the study.
Pre-assignment Detail	A total of 19 subjects were screened to enroll 11 subjects in the study

Arm/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Period Title: Overall Study
STARTED	6	5
COMPLETED	6	0
NOT COMPLETED	0	5

Baseline Characteristics

Arm/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg	Total
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet	Total of all reporting groups
Overall Participants	6	5	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.2 (1.83)	9.4 (1.52)	8.7 (1.74)
Sex: Female, Male (Count of Participants)
Female	4 66.7%	3 60%	7 63.6%
Male	2 33.3%	2 40%	4 36.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	6 100%	4 80%	10 90.9%
More than one race	0 0%	1 20%	1 9.1%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	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
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [h*ng/mL]	2380 (1880)

2. Primary Outcome

Title	Pharmacokinetics of Fevipiprant by Maximum Plasma Concentration at Steady State (Cmax,ss), After at Least Four Consecutive Days of Dosing
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [ng/mL]	394 (286)

3. Primary Outcome

Title	Pharmacokinetics of Fevipiprant by Oral Clearance at Steady State (CL/F), After at Least Four Consecutive Days of Dosing
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [L/h]	48.2 (32)

4. Secondary Outcome

Title	Pharmacokinetics of Fevipiprant by CL/F
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [L/h]	48.2 (32.0)

5. Secondary Outcome

Title	Pharmacokinetics of Fevipiprant by Tmax,ss
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [h]	1.42 (0.916)

6. Secondary Outcome

Title	Urinary Excretion of Fevipiprant
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [L/h]	6.61 (4.88)

7. Secondary Outcome

Title	Pharmacokinetics of Fevipiprant by Cmin,ss
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [ng/mL]	28.3 (13.8)

8. Secondary Outcome

Title	Pharmacokinetics of the Metabolite CCN362 by AUC0-24h,ss
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [h*ng/mL]	2760 (1210)

9. Secondary Outcome

Title	Pharmacokinetics of the Metabolite CCN362 by Cmax,ss
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [ng/mL]	302 (134)

10. Secondary Outcome

Title	Pharmacokinetics of the Metabolite CCN362 by Cmin,ss
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [ng/mL]	33.6 (22.6)

11. Secondary Outcome

Title	Pharmacokinetics of the Metabolite CCN362 by Tmax,ss
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [h]	2.69 (1.20)

12. Secondary Outcome

Title	Urinary Excretion of the Metabolite, CCN362
Description	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.

Outcome Measure Data

Analysis Population Description

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/Group Title	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet	QAW039 375 mg Chewable tablet
Measure Participants	6	0
Mean (Standard Deviation) [L/h]	5.10 (1.96)

Adverse Events

Time Frame	Adverse events (AEs) are presented from first dose of study treatment until last dose of study treatment plus 7 days post treatment. Serious AEs are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment, up to maximum duration of 38 weeks.
Arm/Group Title	Cohort A Fevipiprant 75 mg		Cohort B Feviprant 375 mg
Arm/Group Description	QAW039 75 mg Chewable tablet		QAW039 375 mg Chewable tablet
All Cause Mortality
	Cohort A Fevipiprant 75 mg		Cohort B Feviprant 375 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)
Serious Adverse Events
	Cohort A Fevipiprant 75 mg		Cohort B Feviprant 375 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Cohort A Fevipiprant 75 mg		Cohort B Feviprant 375 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.