A randomized, double-blind study to compare the efficacy and safety of two doses of mometasone furoate delivered via Breezhaler® or Twisthaler® in patients with asthma

Buhl, Roland; Tanase, Ana-Maria; Hosoe, Motoi; Cao, Weihua; Demin, Ivan; Bartels, Christian; Jauernig, Juergen; Ziegler, Dominik; Patalano, Francesco; Hederer, Bettina; Kanniess, Frank; Tillmann, Hanns-Christian

doi:10.1016/j.pupt.2020.101919

Cited by 14 publications

(14 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 The choice of dose was corroborated by pharmacodynamics studies during the development programme, which confirmed mometasone doses in Breezhaler in terms of FEV 1 . 21 An in-vitro component interaction study showed an increase in mometasone fine particle mass in MF-IND-GLY, 22 All patients were trained on all devices and dosing was witnessed at site during visits to ensure correct technique. At screening, all patients were provided with a salbutamol or albuterol metered-dose inhaler as rescue medication.…”

Section: Methodsmentioning

confidence: 99%

Once-daily, single-inhaler mometasone–indacaterol–glycopyrronium versus mometasone–indacaterol or twice-daily fluticasone–salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study

Kerstjens

Máspero²,

Chapman

et al. 2020

The Lancet Respiratory Medicine

Self Cite

112

174

View full text Add to dashboard Cite

show abstract

Section: Methodsmentioning

confidence: 99%

Once-daily, single-inhaler mometasone–indacaterol–glycopyrronium versus mometasone–indacaterol or twice-daily fluticasone–salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study

Kerstjens

Máspero²,

Chapman

et al. 2020

The Lancet Respiratory Medicine

Self Cite

112

174

View full text Add to dashboard Cite

show abstract

“…The medium and high MF doses (80 μg and 160 μg) as part of the IND/GLY/MF combination delivered via the Breezhaler ® device are comparable to the 400 μg and 800 µg doses of MF delivered by the Twisthaler device, respectively. The high MF dose (320 μg) as part of the IND/MF combination delivered via the Breezhaler ® device is comparable to the 800 μg dose of MF delivered by the Twisthaler device [22]. The high MF dose (160 μg) as part of the IND/GLY/MF combination is comparable to the high MF dose (320 μg) as part of the IND/MF combination in terms of systemic exposure [23].…”

Section: Study Objectivesmentioning

confidence: 78%

Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler® device (IND/GLY/MF) is being developed for treatment of asthma. This study compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d. Methods This was a single-center, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 μg (inhaled corticosteroid [ICS] medium-dose) or 150/50/160 μg o.d. (ICS high-dose) for 14 days in each period. Pharmacokinetics were characterized up to 24 h post-dose on Days 1 and 14. Results In total, 16 Japanese (median age 31 years [range 20–40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range 21–43 years], mean weight 75.0 kg) were randomized. Geometric mean ratios (Japanese/Caucasian) [90% confidence interval (CI)] for Cmax for IND, GLY and MF at the high ICS dose on Day 14 were 1.31 [1.13, 1.51] 1.38 [1.13, 1.69] and 1.07 [0.969, 1.18], respectively. Geometric mean ratios (Japanese/Caucasian) [90% CI] for AUC0–24h on Day 14 for IND, GLY and MF at the high ICS dose were 1.17 [1.01, 1.35], 1.05 [0.920, 1.20] and 1.15 [1.05, 1.27] respectively. Similar trends were noted for all components for the medium ICS dose treatment. IND/GLY/MF was safe and well tolerated; no AEs suspected to be study drug-related were observed. Conclusion Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as a fixed-dose combination were comparable between Japanese and Caucasian subjects. The IND/GLY/MF combination at the administrated doses was safe and well tolerated in both ethnic groups. Trial registration Japan Registry of Clinical Trial: jRCT2031200227, retrospectively registered on 04, December, 2020.

show abstract

“…A 3-step bridging approach identified doses of MF in the Breezhaler ® device that were comparable to the corresponding doses of MF in the Twisthaler ® device. The approach has been described previously [20]. Table 2…”

Section: Methodsmentioning

confidence: 99%

“…However, popPK models for both IND and GLY have been established when administered as IND/GLY to COPD patients [ 17 ]. The present analysis is based on 3 studies (PALLADIUM [ 18 ], IRIDIUM [ 19 ] and E2201 [ 20 ]) conducted in patients with asthma for which key design elements are provided in Table 1 . The current analysis, utilising different FDC studies, aimed to identify the structural popPK models describing the pharmacokinetics of IND, GLY and MF, and to estimate the effect of covariates on the pharmacokinetics of IND, GLY and MF, including the effect of Japanese ethnicity in patients with asthma.…”

Section: Introductionmentioning

confidence: 99%

“…200 μg o.d. −25 min, 15 min, 1 h on Days 30 and 84 Separate LCMS/MS methods for each analyte LLOQs: IND: 10 pg/mL MF: 0.25 pg/mL E2201 [ 20 ] NCT01555151 Randomised, double-blind, double-dummy, 4-week treatment, parallel-group study 179 MF via Breezhaler ® MF via Breezhaler ® MF via Twisthaler ® MF via Twisthaler ® 80 μg o.d. 320 μg o.d.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Population Pharmacokinetic Analysis of Indacaterol/Glycopyrronium/Mometasone Furoate After Administration of Combination Therapies Using the Breezhaler® Device in Patients with Asthma

Bartels

Jain

Yu³

et al. 2021

Eur J Drug Metab Pharmacokinet

Self Cite

View full text Add to dashboard Cite

Background and Objective Clinical evidence suggests no clinically relevant pharmacokinetic interactions between indacaterol (IND), glycopyrronium (GLY) and mometasone furoate (MF). A population pharmacokinetic (popPK) analysis was conducted to identify structural models describing systemic pharmacokinetic profiles of IND, GLY and MF, and estimate the effect of covariates on their pharmacokinetics following inhalation as IND/GLY/MF. Methods Pharmacokinetic data from 698 patients with asthma were pooled from two Phase III studies that evaluated IND/ MF medium-(150/160 µg) and high-dose (150/320 µg), IND/GLY/MF medium-(150/50/80 μg) and high-dose (150/50/160 μg), and a device bridging Phase II study with MF. One popPK model was developed each for IND, GLY and MF using a nonlinear mixed-effect modelling approach. Maximal and trough plasma concentrations were compared across formulations and studies, including data for IND/GLY from chronic obstructive pulmonary disease (COPD) patients. The effect of predefined covariates on the pharmacokinetics of components was evaluated using a full covariate modelling approach. Results The final pharmacokinetic models were two-compartment disposition models with first-order elimination and sequential zero-order/first-order absorption (IND), with bolus administration and first-order elimination (GLY), and with mixed zero-order/first-order absorption and first-order elimination (MF). All model parameters were estimated with good precision (% relative standard error: IND and MF ≤25%; GLY <10%). No clinically relevant covariate effect was observed on the pharmacokinetics of IND, GLY and MF. IND and GLY pharmacokinetic profiles were similar across different formulations. Conclusion Two-compartment popPK models adequately described the pharmacokinetics of IND, GLY and MF. The effect of covariates was not clinically relevant. The pharmacokinetic profiles of MF were comparable for combination products at corresponding medium-or high-dose inhaled corticosteroids. On a population level, the pharmacokinetics of IND and GLY were comparable between patients with asthma and COPD.

show abstract

A randomized, double-blind study to compare the efficacy and safety of two doses of mometasone furoate delivered via Breezhaler® or Twisthaler® in patients with asthma

Cited by 14 publications

References 16 publications

Once-daily, single-inhaler mometasone–indacaterol–glycopyrronium versus mometasone–indacaterol or twice-daily fluticasone–salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study

Once-daily, single-inhaler mometasone–indacaterol–glycopyrronium versus mometasone–indacaterol or twice-daily fluticasone–salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study

Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects

Population Pharmacokinetic Analysis of Indacaterol/Glycopyrronium/Mometasone Furoate After Administration of Combination Therapies Using the Breezhaler® Device in Patients with Asthma

Contact Info

Product

Resources

About