Trial Outcomes & Findings for Study to Compare the Pharmacokinetics of Mometasone Furoate Alone and in Combination With Indacaterol in Patients ≥ 6 to < 12 Years Old With Asthma (NCT NCT04589663)

Last Updated: 2023-10-13

Results Overview

Mometasone furoate plasma concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Cmax of mometasone furoate was determined with Phoenix WinNonlin (Version 8.0 or higher). A correction factor was applied to MF pharmacokinetic parameters to consider the first-dose effect that is based on the fact that the participants in this study received a single dose from single unused (unprimed) C1 and TH devices. Unprimed devices are not coated with the formulation, and therefore may lead to lower fine particle mass (FPM) and delivered dose compared to later doses actuated from the device throughout its use time. The first-dose correction factor (FPMprimed (MF) / FPMunprimed (MF)) for MF delivered via TH was 1.26 and for MF delivered via C1 it was 1.62.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

pre-dose, 0.5, 1, 2, 3 and 6 hours post-dose on Day 1 and Day 6-9

Results posted on

2023-10-13

Participant Flow

Participants were recruited from 3 sites in 2 countries

Participants underwent a Screening period of up to 14 days

Participant milestones

Participant milestones
Measure	MF Followed by QMF149 Single inhaled dose of mometasone furoate on Day 1 delivered via TH inhaler followed by 4-7 days of washout. On Day 6-9, single inhaled dose of QMF149 delivered via C1 inhaler.
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Compare the Pharmacokinetics of Mometasone Furoate Alone and in Combination With Indacaterol in Patients ≥ 6 to < 12 Years Old With Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MF Followed by QMF149 n=24 Participants Single inhaled dose of mometasone furoate on Day 1 delivered via TH inhaler followed by 4-7 days of washout. On Day 6-9, single inhaled dose of QMF149 delivered via C1 inhaler.
Age, Continuous	9.0 Years STANDARD_DEVIATION 1.46 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants
Race (NIH/OMB) More than one race	15 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: pre-dose, 0.5, 1, 2, 3 and 6 hours post-dose on Day 1 and Day 6-9

Population: The overall number of participants analyzed includes all participants with evaluable data for the endpoint.

Outcome measures

Outcome measures
Measure	MF 100 ug Via Twisthaler n=23 Participants Single inhaled dose of mometasone furoate on Day 1 delivered via TH inhaler followed by 4-7 days of washout	QMF149 75/40 ug Via Concept 1 n=24 Participants Single inhaled dose of QMF149 delivered via C1 inhaler on Day 6-9
Maximum Observed Mometasone Furoate Plasma Concentration (Cmax)	51.9 pg/mL Standard Deviation 23.5	53.5 pg/mL Standard Deviation 16

PRIMARY outcome

Timeframe: pre-dose, 0.5, 1, 2, 3 and 6 hours post-dose on Day 1 and Day 6-9

Population: The overall number of participants analyzed includes all participants with evaluable data for the endpoint.

AUC0-6h of mometasone furoate was determined using non-compartment methods with Phoenix WinNonlin (Version 8.0 or higher). The linear trapezoidal rule was used for AUC0-6h calculation. A correction factor was applied to MF pharmacokinetic parameters to consider the first-dose effect that is based on the fact that the participants in this study received a single dose from single unused (unprimed) C1 and TH devices. Unprimed devices are not coated with the formulation, and therefore may lead to lower fine particle mass (FPM) and delivered dose compared to later doses actuated from the device throughout its use time. The first-dose correction factor (FPMprimed (MF) / FPMunprimed (MF)) for MF delivered via TH was 1.26 and for MF delivered via C1 it was 1.62.

Outcome measures

Outcome measures
Measure	MF 100 ug Via Twisthaler n=18 Participants Single inhaled dose of mometasone furoate on Day 1 delivered via TH inhaler followed by 4-7 days of washout	QMF149 75/40 ug Via Concept 1 n=23 Participants Single inhaled dose of QMF149 delivered via C1 inhaler on Day 6-9
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time Point 6h (AUC0-6h) of Mometasone Furoate	208 h*pg/mL Standard Deviation 102	176 h*pg/mL Standard Deviation 57.5

SECONDARY outcome

Timeframe: pre-dose, 0.25 and 1 hour post-dose on Day 6-9

Population: The overall number of participants analyzed includes all participants. The number analyzed per row represents participants with evaluable data at each time point.

Systemic exposure to indacaterol in plasma following sparse pharmacokinetic (PK) sampling on Day 6-9 after inhalation of QMF149. A correction factor was applied to indacaterol plasma concentrations to consider the first-dose effect that is based on the fact that the participants in this study received a single dose from single unused (unprimed) C1 and TH devices. Unprimed devices are not coated with the formulation, and therefore may lead to lower fine particle mass (FPM) and delivered dose compared to later doses actuated from the device throughout its use time. The first-dose correction factor (FPMprimed (indacaterol) / FPMunprimed (indacaterol)) for indacaterol delivered via C1 was 2.0.

Outcome measures

Outcome measures
Measure	MF 100 ug Via Twisthaler n=24 Participants Single inhaled dose of mometasone furoate on Day 1 delivered via TH inhaler followed by 4-7 days of washout	QMF149 75/40 ug Via Concept 1 Single inhaled dose of QMF149 delivered via C1 inhaler on Day 6-9
Systemic Exposure to Indacaterol in Plasma Pre-dose	0 pg/mL Standard Deviation 0	—
Systemic Exposure to Indacaterol in Plasma 0.25 hours post-dose	102.0 pg/mL Standard Deviation 54.9	—
Systemic Exposure to Indacaterol in Plasma 1 hours post-dose	62.3 pg/mL Standard Deviation 26.2	—

Adverse Events

MF 100 ug Via Twisthaler

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

QMF149 75/40 ug Via Concept 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Total

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	MF 100 ug Via Twisthaler n=24 participants at risk Single inhaled dose of mometasone furoate on Day 1 delivered via TH inhaler followed by 4-7 days of washout	QMF149 75/40 ug Via Concept 1 n=24 participants at risk Single inhaled dose of QMF149 delivered via C1 inhaler on Day 6-9	Total n=24 participants at risk Total
Product Issues Device failure	8.3% 2/24 • Adverse events were reported from the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 39 days. Any sign or symptom that occurs during the study treatment plus the 30 days post treatment	0.00% 0/24 • Adverse events were reported from the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 39 days. Any sign or symptom that occurs during the study treatment plus the 30 days post treatment	8.3% 2/24 • Adverse events were reported from the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 39 days. Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
Infections and infestations Influenza	4.2% 1/24 • Adverse events were reported from the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 39 days. Any sign or symptom that occurs during the study treatment plus the 30 days post treatment	0.00% 0/24 • Adverse events were reported from the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 39 days. Any sign or symptom that occurs during the study treatment plus the 30 days post treatment	4.2% 1/24 • Adverse events were reported from the start of treatment to 30 days after end of treatment, assessed up to maximum duration of 39 days. Any sign or symptom that occurs during the study treatment plus the 30 days post treatment

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER