Prescribing information

 

Efficacy and safety of inhaled once-daily low-dose indacaterol acetate/mometasone furoate (IND/MF) in patients with inadequately controlled asthma: Phase III randomised QUARTZ study findings1

 

What was already known?

  • Many patients with asthma remain symptomatic despite receiving inhaled corticosteroid (ICS) monotherapy1
  • The Global Initiative for Asthma (GINA) 2020 guidelines recommend adding a long-acting beta2 agonist (LABA) to ICS monotherapy as the preferred controller and maintenance therapy in patients with inadequately controlled asthma2

 

Why was QUARTZ conducted?

  • The addition of a LABA to ICS monotherapy helps in achieving asthma control by reducing symptoms and improving lung function3–6
  • Several twice-daily LABA/ICS combinations are currently available, along with one once-daily combination (fluticasone furoate/vilanterol), for GINA Step 3–5 treatment of asthma2,7–12
  •  There is a need to evaluate once-daily dosing regimens for effective asthma treatment, which may provide adherence benefits1

 

Trial design1

fs_2_quartz_pic1

 

All treatments were administered in the evening.

Adapted from Kornmann O, et al. 2020. 
IND/MF was administered via Breezhaler® and MF via Twisthaler®.
Trial identifier: QVM149B2303. More information can be found at: https://clinicaltrials.gov/ct2/show/NCT02892344. MF 200 µg (once-daily) via Twisthaler® is equivalent to MF 80 µg (once-daily) via Breezhaler®.
IND/MF low-dose = IND/MF 150/80 µg (once-daily); MF low-dose = MF 200 µg (once-daily).

Objectives and endpoints1

To evaluate efficacy and safety of IND/MF low-dose (once-daily), delivered via Breezhaler®,  vs. MF low-dose (once-daily), delivered via Twisthaler®, in terms of lung function (trough forced expiratory volume in one second [FEV1]) and asthma control (Asthma Control Questionnaire [ACQ-7] score) in inadequately controlled asthma patients.

Primary endpoint: Demonstrate superiority in trough FEV1 of IND/MF low-dose vs. MF low-dose after 12 weeks of treatment

Key secondary endpoint: Demonstrate superiority in ACQ-7 score of IND/MF low-dose vs. MF low-dose after 12 weeks of treatment

Other secondary analyses:13

Assessment of IND/MF low-dose vs. MF low-dose with respect to:

  • Trough FEV1 on Day 2; pre-dose FEV1 at Week 4; forced vital capacity (FVC) and forced expiratory flow between 25% and 75% of FVC over 12 weeks of treatment; morning and evening peak expiratory flow over 4 and 12 weeks of treatment
  • ACQ-7 at Week 4; ACQ-7 responders (patients achieving minimal clinically important difference [MCID] of ≥0.5) at Week 12; symptoms as recorded in an eDiary over weeks of treatment; rescue medication use and rescue medication-free days over 12 weeks of treatment
  • Asthma Quality of Life Questionnaire over 12 weeks of treatment
  • Asthma exacerbations (moderate or severe, severe, all) over 12 weeks of treatment
  • Safety and tolerability1

 

Included patients1

  • 802 male and female adults and adolescents aged ≥12 and ≤75 years with a documented diagnosis of asthma for a period of ≥3 months prior to screening, who were taking low-dose ICS (with or without controller, e.g. LABA) for at least 1 month prior to screening visit
  • Patients had FEV1 <90% predicted and were symptomatic (as measured by ACQ-7 ≥1.5)

 

What are the results and why are they relevant?1

QUARTZ demonstrated that IND/MF low-dose significantly improved lung function and asthma control after 12 weeks of treatment vs. MF low-dose, in symptomatic adult and adolescent patients with inadequately controlled asthma.

 

Lung function1

The primary endpoint was met. IND/MF low-dose demonstrated statistically significant improvements in trough FEV1 compared to MF low-dose after 12 weeks of treatment – mean difference 182 mL (95% confidence interval [CI]: 148, 217; p<0.001).

 

Trough FEV1 at Week 12: IND/MF vs. MF (primary endpoint)

 

Data are presented as least squares (LS) mean.
IND/MF low-dose = IND/MF 150/80 µg (once-daily); MF low-dose = MF 200 µg (once-daily).

Asthma control1

The key secondary endpoint was met. IND/MF low-dose demonstrated statistically significant improvements in asthma control compared with MF low-dose, as measured by ACQ-7 after 12 weeks of treatment – mean treatment difference: -0.218 (95% CI: -0.293, -0.143; p<0.001).

 

ACQ-7 at Week 12: IND/MF vs. MF (key secondary endpoint)

 

Data are presented as LS mean.
IND/MF low-dose = IND/MF 150/80 μg (once-daily); MF low-dose = MF 200 μg (once-daily).

 

The ACQ-7 responder analysis was not controlled for multiplicity; inferences based on these data cannot be made due to lack of power.

In addition, clinically meaningful improvement in ACQ-7 was supported by a responder analysis.

 

ACQ-7 responder rates at Week 12: IND/MF vs. MF (secondary analysis)

 

*Patients with an improvement of ≥0.5 points (MCID) in ACQ-7 score.
IND/MF low-dose = IND/MF 150/80 µg (once-daily); MF low-dose = MF 200 µg (once-daily).

 

These secondary analyses relating to rescue medication and exacerbations were not controlled for multiplicity; inferences based on these data cannot be made due to lack of power.

 

Rescue medication1

There was a treatment difference in mean daily number of puffs of rescue medication of -0.26 between the groups (smaller in IND/MF group; 95% CI: -0.37,-0.14).

There was a treatment difference in rescue medication-free days of 8.1% between the groups (greater in IND/MF group; 95% CI: 4.3,11.8).

 

Exacerbations1

There was a treatment difference in number of patients suffering all exacerbations of 70% between the groups (smaller in IND/MF group; rate ratio 0.30 [95% CI: 0.18, 0.50]).

 

Safety

IND/MF low-dose was generally well-tolerated. The overall incidence of adverse events was lower in the IND/MF low-dose group vs. MF low-dose group (32.3% vs. 38.3% respectively)

  • Common adverse events (with a frequency of ≥1%) included asthma exacerbation, nasopharyngitis, pharyngitis, sinusitis, overdose, cough, dysphonia, allergic rhinitis, headache, upper respiratory tract infection and influenza13
  • Serious adverse events included asthma exacerbation, prostate cancer, osteoarthritis, incisional hernia, oral abscess, dental cyst13
  • No deaths were reported during the study1,13

 

Implications for clinical practice1

QUARTZ demonstrated that IND/MF low-dose significantly improved trough FEV1 and asthma control vs. MF low-dose, and was generally well-tolerated in adult and adolescent patients with inadequately controlled asthma: 

  • Once-daily IND/MF low-dose can be a potential treatment option for adult and adolescent patients with asthma who remain inadequately controlled on ICS
  • Data from this study add to the existing evidence supporting the efficacy of LABA/ICS over ICS alone, and the efficacy of a once-daily combination of IND/MF low-dose in patients with inadequately controlled asthma

 

Indication: ATECTURA® BREEZHALER® is indicated as a maintenance treatment of asthma in adults and adolescents 12 years of age and older not adequately controlled with inhaled corticosteroids and inhaled short-acting beta2-agonists.14

ACQ-7, Asthma Control Questionnaire-7; CI, confidence interval; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; GINA, Global Initiative for Asthma; ICS, inhaled corticosteroid; IND, indacaterol acetate; LABA, long-acting beta2-agonist; LS, least squares; MCID, minimal clinically important difference; MF, mometasone furoate.

Reference

  1. Kornmann O et al. Respir Med 2020;161:105809 [Epub ahead of print].
  2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2020. Available at: https://ginasthma.org/wp-content/uploads/ 2020/04/GINA-2020-full-report_-final-_wms.pdf. Date accessed: December 2020.
  3. Bell A & McIvor A. Can Fam Physician 2007;53(4):687–688.
  4. Corren J et al. Respir Med 2013;107:180–195.
  5. Currie G et al. Br J Clin Pharmacol 2003;56(1):11–17.
  6. Rodrigo G & Castro-Rodriguez J. Thorax 2012;67(4):342–349.
  7. Flutiform Summary of Product Characteristics. January 2019.
  8. Relvar Ellipta Summary of Product Characteristics. January 2019.
  9. Seretide Accuhaler Summary of Product Characteristics. November 2019.
  10. Fostair Summary of Product Characteristics. March 2020.
  11. Symbicort Turbuhaler Summary of Product Characteristics. August 2019.
  12. Dulera Patient Information Leaflet. August 2019.
  13. CinicalTrials.gov. NCT02892344. Available at: https://clinicaltrials.gov/ct2/show/NCT02892344. Date accessed: December 2020.
  14. ATECTURA BREEZALER Summary of Product Characteristics.

 

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UK | February 2021 | 103407
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