AsthmaPhase 2NCT04589663
Study to Compare the Pharmacokinetics of Mometasone Furoate Alone and in Combination With Indacaterol in Patients ≥ 6 to < 12 Years Old With Asthma
A Phase 2 study testing Mometasone furoate and QMF149 in people with Asthma, run by Novartis Pharmaceuticals at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 to 11 years
- Conditions the study is for
- Asthma
- What is being tested?
- Mometasone furoate and QMF149
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 7 Jun 2021to 11 Apr 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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:
Show all 27Show fewer
- 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.
- 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.
- Patients who have a clinically significant ECG abnormality or clinically significant abnormal lab values reported at Screening Visit.
- 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).
- 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.
- 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.
- Patient is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
- Pregnant or nursing (lactating) females.
- Inability to properly train in the use of the In-Check DIAL® at screening (at the investigator's discretion).
- Inability to properly train in the use of the Twisthaler® or Concept 1 Breezhaler® prior to dosing (at the investigator's discretion).
- History of paradoxical bronchospasm in response to inhaled medicines.
- Patients receiving any medications in the classes specified in protocol Table 6-2 unless they undergo the required washout period prior to Day 1.
- Patients who are sexually active.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
South Africa2 sites
Novartis Investigative Site
Cape Town, 7531
Novartis Investigative Site
George, Western Cape, 6529
About this study
Official title: 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.
Read the 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.
- Conditions
- Asthma
- Being tested
- Mometasone furoate, QMF149, Standard of Care (Soc)
- Keywords
- QMF149, mometasone furoate, indacaterol, pediatric, asthma, PK
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mometasone furoateDrug
Also called MF
Single inhaled dose of 100 µg mometasone furoate (MF) administered via Twisthaler® on Day 1
QMF149Drug
Single inhaled dose of QMF149 (75/40 µg indacaterol acetate/MF fixed dose combination) administered via Concept 1 device on Day 6-9
Standard of Care (Soc)Drug
Asthma therapy: budesonide and salbutamol being the most frequently used (excluding MF and indacaterol acetate)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Mometasone furoate; Drug: QMF149; Drug: Standard of Care (Soc) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: pre-dose, 0.25 and 1 hour post-dose on Day 6-9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2020
- Study start7 Jun 2021
- Primary completion11 Apr 2022
- Study completion11 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-sequence crossover study
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04589663
- Sponsor's protocol ID
- CQMF149G2203
- Other IDs
- 2020-002036-78
- Status last verified
- Oct 2023
- First submitted
- 7 Oct 2020
- Last updated
- 13 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04589663
- Acronym / sponsor ID
- CQMF149G2203
- Conditions
- Asthma
- Keywords
- QMF149, mometasone furoate, indacaterol, pediatric, asthma, PK
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Jun 2021 (actual)
- Primary completion
- 11 Apr 2022 (actual)
- Study completion
- 11 Apr 2022 (actual)
- First posted
- 19 Oct 2020 (actual)
- Results
- Posted 27 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-sequence crossover study
| Arm | Type | Receives |
|---|---|---|
| MF followed by QMF149 | Experimental | Drug: Mometasone furoate, Drug: QMF149, Drug: Standard of Care (Soc)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. |
Who may qualify
- Ages
- 6 to 11 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (27 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mometasone furoateAlso: MFSingle inhaled dose of 100 µg mometasone furoate (MF) administered via Twisthaler® on Day 1 | Drug | MF followed by QMF149 |
| QMF149Single inhaled dose of QMF149 (75/40 µg indacaterol acetate/MF fixed dose combination) administered via Concept 1 device on Day 6-9 | Drug | MF followed by QMF149 |
| Standard of Care (Soc)Asthma therapy: budesonide and salbutamol being the most frequently used (excluding MF and indacaterol acetate) | Drug | MF followed by QMF149 |
Primary outcome
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.
1 secondary outcome
Systemic Exposure to Indacaterol in Plasma
Time frame: pre-dose, 0.25 and 1 hour post-dose on Day 6-9
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mometasone furoate and QMF149 in people with Asthma, run by Novartis Pharmaceuticals at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Africa, Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2023.