Pharmacokinetics of mometasone furoate delivered via two dry powder inhalers

Vaidya, Soniya; Ziegler, Dominik; Tanase, Ana-Maria; Malmqvist, Ulf; Kanniess, Frank; Hederer, Bettina; Hosoe, Motoi

doi:10.1016/j.pupt.2021.102019

Cited by 7 publications

(5 citation statements)

References 13 publications

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“…All monocomponents of IND/GLY/MF act locally in the lungs. We investigated the systemic pharmacokinetics which depend on the amount of drug absorbed from the lungs and from the gastrointestinal tract (for inhaled IND, GLY and MF, absorption occurs predominantly via the lungs [24][25][26][27][28]). For inhaled drug delivery, it is challenging to evaluate the relationship between plasma drug concentrations and pulmonary efficacy due to potentially different drug deposition patterns following inhaled delivery and difficulty in collecting samples to determine drug concentrations in the lung [29,30].…”

Section: Discussionmentioning

confidence: 99%

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

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…IND and GLY have been approved for inhalation via the Breezhaler ® device, whereas MF is approved for inhalation via the Twisthaler ® device [ 15 , 17 , 23 ]. Therefore, a stepwise bridging approach was implemented to facilitate the bridging of MF doses from Twisthaler ® to Breezhaler ® and in IND/GLY/MF and IND/MF formulations [ 27 , 28 ]. MF at doses of 80, 160, and 320 µg delivered via the Breezhaler ® device was assessed to be comparable to MF 200, 400, and 800 µg (two inhalations of 400 µg) delivered via the Twisthaler ® device (Table 1 ), and these adjusted doses were confirmed via a pharmacokinetic/pharmacodynamic study program at different MF dose levels [ 27 – 30 ].…”

Section: Approach To An Accelerated and Unique Drug Development Strategymentioning

confidence: 99%

“…Therefore, a stepwise bridging approach was implemented to facilitate the bridging of MF doses from Twisthaler ® to Breezhaler ® and in IND/GLY/MF and IND/MF formulations [ 27 , 28 ]. MF at doses of 80, 160, and 320 µg delivered via the Breezhaler ® device was assessed to be comparable to MF 200, 400, and 800 µg (two inhalations of 400 µg) delivered via the Twisthaler ® device (Table 1 ), and these adjusted doses were confirmed via a pharmacokinetic/pharmacodynamic study program at different MF dose levels [ 27 – 30 ]. The confirmed doses of MF were then used for the IND/MF FDC.…”

Section: Approach To An Accelerated and Unique Drug Development Strategymentioning

confidence: 99%

A Review of the Unique Drug Development Strategy of Indacaterol Acetate/Glycopyrronium Bromide/Mometasone Furoate: A First-in-Class, Once-Daily, Single-Inhaler, Fixed-Dose Combination Treatment for Asthma

et al. 2022

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A novel, once-daily (o.d.), fixed-dose combination (FDC) of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF), delivered by the inhaler Breezhaler Ò device, is the first long-acting beta2adrenergic agonist/long-acting muscarinic antagonist/inhaled corticosteroid (LABA/LAMA/ICS) therapy to be approved for maintenance treatment of asthma in adults inadequately controlled on LABA/ICS. The approval of IND/GLY/MF in the European Union (EU) also included an optional electronic sensor and smartphone (or other suitable device) application, making it the first ''digital companion'' that can be prescribed with an asthma medication. As a result, the European Medicines Agency included this approval as one of the ''outstanding contributions

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“…15 Notably, due to formulation characteristics, the doses of mometasone in the MF-IND-GLY combinations were halved compared to the corresponding MF-IND comparators. 15,16 ARGON was a 24-week, open-label RCT that investigated the non-inferiority of SITT (MF/IND/GLY) once-daily delivered via the DPI Breezhaler ® vs. FP/SLM high dose (twice-daily) delivered via the DPI Diskus ® plus tiotropium (TIO; once-daily) delivered via Respimat ® in two separate devices on the Asthma Quality of Life Questionnaire (AQLQ) in patients with uncontrolled asthma. 17 Of note, it did not explore other outcomes such as exacerbations.…”

Section: Sys Temati C Re Vie W Of Avail Ab Le E Viden Cementioning

confidence: 99%

“… 15 Notably, due to formulation characteristics, the doses of mometasone in the MF‐IND‐GLY combinations were halved compared to the corresponding MF‐IND comparators. 15 , 16 …”

Section: Systematic Review Of Available Evidencementioning

confidence: 99%

Single inhaler triple therapy (SITT) in asthma: Systematic review and practice implications

Agustí

Fabbri

Lahousse

et al. 2021

Allergy

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A significant number of patients with asthma remain uncontrolled despite treatment with inhaled corticosteroids (ICS) and long‐acting β2 adrenergic bronchodilators (LABA). The addition of long‐acting antimuscarinic agents (LAMA) can improve the management of asthma in these patients. Recently, three novel triple therapy (ICS/LABA/LAMA) formulations in a single‐inhaler device (SITT) have been investigated in patients with uncontrolled asthma despite ICS/LABA treatment. Here, we review systematically the evidence available to date in relation to SITT in patients with uncontrolled asthma despite ICS‐LABA treatment and conclude that SITT is a safe and effective therapeutic alternative in these patients. We also discuss how to position this new therapeutic alternative in their practical clinical management as well as the opportunities and challenges that it may generate for patients, physicians, and payers.

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Pharmacokinetics of mometasone furoate delivered via two dry powder inhalers

Cited by 7 publications

References 13 publications

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

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

A Review of the Unique Drug Development Strategy of Indacaterol Acetate/Glycopyrronium Bromide/Mometasone Furoate: A First-in-Class, Once-Daily, Single-Inhaler, Fixed-Dose Combination Treatment for Asthma

Single inhaler triple therapy (SITT) in asthma: Systematic review and practice implications

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