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

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

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.

Inclusion Criteria:

1. Male and female children ≥ 6 years and < 12 years at the time of study entry.
2. 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.
3. Confirmed documented diagnosis of asthma, as defined by national or international asthma guidelines for at least 6 months prior to study enrollment.
4. Patients using low dose ICS as asthma controller therapy for at least 4 weeks prior to first treatment.
5. Patients who are familiar with the use of an inhaler device.
6. 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.
7. 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:

1. 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.

2. Patients with weight < 17kg at screening.

3. Patients currently taking MF products for any reason at least 7 days prior to Day 1. 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.

4. Patients on medium- and high- dose ICS or any dose ICS/LABA combination.

5. 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.

6. 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

7. History of chronic lung disease other than asthma within 3 months of first treatment visit (Day 1), cystic fibrosis, mycobacterial or other infection (including active SARS-CoV-2, tuberculosis or atypical mycobacterial disease).

8. History of active bacterial, viral or fungal infection (including SARS-CoV-2) within 6 weeks of first treatment visit (Day 1).

9. Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of first treatment visit (Day 1).

10. Patients who, in the opinion of the investigator, are not able to comply with study treatment or who have any medical or mental disorder, situation, or diagnosis, which could interfere with the proper completion of the study protocol requirements or pose a safety risk while participating in the study.

11. Parent/guardian has a history of psychiatric disease, intellectual deficiency, substance abuse, or other condition (e.g. inability to read, comprehend and write) which will limit the validity of consent for their child to participate in this study.

12. Hemoglobin levels outside normal ranges at screening.

13. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the patient in case of participation in the study.

14. Patients who have a clinically significant ECG abnormality or clinically significant abnormal lab values reported at Screening Visit.

15. Patients with a history of long QT syndrome or whose corrected QT interval (QTc) measured at Screening Visit (Fridericia method) is prolonged (≥ 450 msec for males and females 6 - 12 years old).

16. Use of any prescription drugs, herbal supplements, prescribed medicinal use of cannabis/marijuana, within four weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements within two weeks prior to initial dosing. If needed, (i.e. an incidental and limited need) paracetamol/acetaminophen is acceptable, but must be documented in the Concomitant medications / Significant non-drug therapies page of the CRF.

17. History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

18. Patient is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.

19. Pregnant or nursing (lactating) females.

20. Inability to properly train in the use of the In-Check DIAL® at screening (at the investigator's discretion).

21. Inability to properly train in the use of the Twisthaler® or Concept 1 Breezhaler® prior to dosing (at the investigator's discretion).

22. History of paradoxical bronchospasm in response to inhaled medicines.

23. Patients receiving any medications in the classes specified in protocol Table 6-2 unless they undergo the required washout period prior to Day 1.

24. Patients who are sexually active.