This clinical study was designed to assess the pharmacokinetics, safety and tolerability of single inhaled doses of mometasone furoate (MF) when administered alone via MF Twisthaler® (TH) or as an indacaterol acetate/MF fixed dose combination (QMF149) via the Concept 1 (C1) device in pediatric asthma patients.
This study was an open-label, two-period, single-sequence crossover study that consisted of four distinct study periods: * Screening: Participants underwent a screening period of up to 14 days where were assessed for eligibility. * First Treatment: On the first treatment visit (Day 1) participants received a single inhaled dose of 100 μg MF administered via the TH device followed by a 4-7-day washout period. * Second Treatment: On the second treatment visit (Day 6-9) participants received a single inhaled dose of 75/40 μg indacaterol acetate/MF fixed dose combination (FDC) (QMF149) via C1 (Breezhaler®) device. Participants were allowed to use rescue medication (as needed) and potentially their Standard of Care (SoC) asthma therapy (excluding MF and indacaterol acetate). * Safety Follow-up: Upon completion of the treatment period, participants were followed up for safety assessments for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Single inhaled dose of 100 µg mometasone furoate (MF) administered via Twisthaler® on Day 1
Single inhaled dose of QMF149 (75/40 µg indacaterol acetate/MF fixed dose combination) administered via Concept 1 device on Day 6-9
Asthma therapy: budesonide and salbutamol being the most frequently used (excluding MF and indacaterol acetate)
Novartis Investigative Site
Nagykanizsa, Hungary
Novartis Investigative Site
George, Western Cape, South Africa
Novartis Investigative Site
Cape Town, South Africa
Maximum Observed Mometasone Furoate Plasma Concentration (Cmax)
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.
Time frame: pre-dose, 0.5, 1, 2, 3 and 6 hours post-dose on Day 1 and 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
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.
Time frame: pre-dose, 0.5, 1, 2, 3 and 6 hours post-dose on Day 1 and Day 6-9
Systemic Exposure to Indacaterol in Plasma
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.
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Time frame: pre-dose, 0.25 and 1 hour post-dose on Day 6-9