An Open-label, Two-period, Single-sequence, Crossover Study to Compare the Systemic Exposure of a Single Inhaled Dose of Mometasone Furoate (MF) When Administered Alone Via the MF Twisthaler® (TH) to a Single Inhaled Dose of QMF149 Indacaterol Acetate/MF Fixed Dose Combination When Administered Via the Concept 1 (C1) Breezhaler® Device in ≥ 6 to < 12 Year Old Asthma Patients
Overview
- Phase
- Phase 2
- Intervention
- Mometasone furoate
- Conditions
- Asthma
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Maximum Observed Mometasone Furoate Plasma Concentration (Cmax)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female children ≥ 6 years and \< 12 years at the time of study entry.
- •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.
- •Patients using low dose ICS as asthma controller therapy for at least 4 weeks prior to first treatment.
- •Patients who are familiar with the use of an inhaler device.
- •Patients must be able to comply with the Study Visit Assessment Schedule which includes approximately 7 hours on two occasions, and agree to blood draws as scheduled.
- •Parents/ legal guardian must be willing and able to attend study visits and assist the child with the procedures outlined in the protocol
Exclusion Criteria
- •Use of other investigational drugs within 5 half-lives of enrollment, or \[within 30 days (for small molecules) /until the expected PD effect has returned to baseline (for biologics)\], whichever is longer.
- •Patients with weight \< 17kg at screening.
- •Patients currently taking MF products for any reason at least 7 days prior to Day
- •Patients can enroll if MF was discontinued at least 7 days prior to Day 1 and MF is substituted with a different steroid during entire study duration to avoid its potential impact on PK assessment. These MF products include inhalation, topical and/or nasal spray formulations.
- •Patients on medium- and high- dose ICS or any dose ICS/LABA combination.
- •Patients taking maintenance controller therapy (eg LABAs and theophylline) within 4 weeks of screening or during the study. LTRAs are permitted provided that patients have been on a stable dose for 4 weeks prior to screening. Patients using short-acting bronchodilators on occasional basis as rescue medication can enroll, however, these medications must be withheld at least 8 hours prior to study dosing visits and during PK sampling.
- •Contraindicated for treatment with, or having a history of reactions/hypersensitivity to any of the following inhaled drugs, drugs of a similar class, or any component there of:
- •Adrenoreceptor agonist agent Lactose or any of the other excipients of the study drug (including patients with history of galactose intolerance, lactase deficiency or glucose-galactose malabsorption)
- •Corticosteroids
- •Indacaterol and/or MF
Arms & Interventions
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.
Intervention: Mometasone furoate
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.
Intervention: QMF149
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.
Intervention: Standard of Care (Soc)
Outcomes
Primary Outcomes
Maximum Observed Mometasone Furoate Plasma Concentration (Cmax)
Time Frame: pre-dose, 0.5, 1, 2, 3 and 6 hours post-dose on Day 1 and Day 6-9
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.
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time Point 6h (AUC0-6h) of Mometasone Furoate
Time Frame: pre-dose, 0.5, 1, 2, 3 and 6 hours post-dose on Day 1 and Day 6-9
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.
Secondary Outcomes
- Systemic Exposure to Indacaterol in Plasma(pre-dose, 0.25 and 1 hour post-dose on Day 6-9)