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

NCT04589663 | Completed Phase 2 Results

• 2 other identifiers: CQMF149G22032020-002036-78
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 3

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.

Conditions

Asthma

Keywords

QMF149; mometasone furoate; indacaterol; pediatric; asthma; PK

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

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

Secondary Outcomes (1)

• Systemic Exposure to Indacaterol in Plasma

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

Study Arms (1)

MF followed by QMF149

EXPERIMENTAL

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.

Drug: Mometasone furoate; Drug: QMF149; Drug: Standard of Care (Soc)

Interventions

Mometasone furoate DRUG

Single inhaled dose of 100 µg mometasone furoate (MF) administered via Twisthaler® on Day 1

Also known as: MF

MF followed by QMF149

QMF149 DRUG

Single inhaled dose of QMF149 (75/40 µg indacaterol acetate/MF fixed dose combination) administered via Concept 1 device on Day 6-9

MF followed by QMF149

Standard of Care (Soc) DRUG

Asthma therapy: budesonide and salbutamol being the most frequently used (excluding MF and indacaterol acetate)

MF followed by QMF149

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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 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.
• 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
• 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).
• History of active bacterial, viral or fungal infection (including SARS-CoV-2) within 6 weeks of first treatment visit (Day 1).
• 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).
• 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.
• 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.
• Hemoglobin levels outside normal ranges at screening.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Nagykanizsa, 8800, Hungary

Location

Novartis Investigative Site

George, Western Cape, 6529, South Africa

Location

Novartis Investigative Site

Cape Town, 7531, South Africa

Location

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Asthma

Interventions

Mometasone Furoate; QMF149; Standard of Care

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-sequence crossover study

Study Record Dates

• First Submitted: October 7, 2020
• First Posted: October 19, 2020
• Study Start: June 7, 2021
• Primary Completion: April 11, 2022
• Study Completion: April 11, 2022
• Last Updated: October 13, 2023
• Results First Posted: July 27, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share

Locations

ZA (2); HU (1)