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

• ClinicalTrials.gov Identifier: NCT03650400
• Recruitment Status: Terminated
• First Posted: August 28, 2018
• Results First Posted: July 20, 2020
• Last Update Posted: December 2, 2020
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Asthma
• Intervention: Drug: Fevipiprant
• Enrollment: 11

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

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
Reason Not Completed
Study terminated by sponsor	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 Number of Baseline Participants		6	5	11
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	6 participants	5 participants	11 participants
		8.2 (1.83)	9.4 (1.52)	8.7 (1.74)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	5 participants	11 participants
	Female	4 66.7%	3 60.0%	7 63.6%
	Male	2 33.3%	2 40.0%	4 36.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	5 participants	11 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	6 100.0%	4 80.0%	10 90.9%
	More than one race	0 0.0%	1 20.0%	1 9.1%
	Unknown or Not Reported	0 0.0%	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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: ng/mL
	28.3 (13.8)

8. Secondary Outcome

Title	Pharmacokinetics of the Metabolite CCN362 by AUC0-24h,ss
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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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
Overall Number of Participants Analyzed	6	0
Mean (Standard Deviation); Unit of Measure: 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.
Adverse Event Reporting Description	[Not Specified]
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 (%)	Affected / at Risk (%)
Total	0/6 (0.00%)	0/5 (0.00%)
Serious Adverse Events
	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/6 (0.00%)	0/5 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort A Fevipiprant 75 mg	Cohort B Feviprant 375 mg
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/6 (0.00%)	0/5 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 882 778 8300
• EMail: Novartis.email@Novartis.com

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT03650400
• Other Study ID Numbers: CQAW039B2201
• First Submitted: August 27, 2018
• First Posted: August 28, 2018
• Results First Submitted: July 1, 2020
• Results First Posted: July 20, 2020
• Last Update Posted: December 2, 2020