Ethnic pharmacokinetic comparison of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) between Asian and Western healthy subjects

Huang, Ying; Assam, Pryseley Nkouibert; Feng, Cong; Su, Rong; Dorinsky, Paul; Gillen, Michael

doi:10.1016/j.pupt.2020.101976

Cited by 3 publications

(7 citation statements)

References 25 publications

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“…Age, gender, ethnicity (Asian and Western [ 15 , 16 ]) and bodyweight have no clinically relevant effects on the pharmacokinetics of budesonide, glycopyrronium and formoterol [ 3 , 4 ]. Budesonide/glycopyrronium/formoterol has not been formally studied in patients with kidney or hepatic impairment.…”

Section: Pharmacokinetic Propertiesmentioning

confidence: 99%

Budesonide/Glycopyrronium/Formoterol: A Review in COPD

Heo

2021

Drugs

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Budesonide/glycopyrronium/formoterol (BREZTRI AEROSPHERE™; TRIXEO AEROSPHERE™) is an inhaled fixed-dose combination of the inhaled corticosteroid (ICS) budesonide, the long-acting muscarinic antagonist (LAMA) glycopyrronium bromide and the long-acting β 2 -agonist (LABA) formoterol fumarate approved for the maintenance treatment of chronic obstructive pulmonary disease (COPD). It is delivered via a pressurized metered-dose Aerosphere inhaler and is formulated using co-suspension delivery technology. In two pivotal phase III trials of 24–52 weeks’ duration, budesonide/glycopyrronium/formoterol reduced the rates of moderate/severe COPD exacerbations and improved lung function to a greater extent than budesonide/formoterol and/or glycopyrronium/formoterol. Budesonide/glycopyrronium/formoterol also demonstrated beneficial effects on dyspnoea, rescue medication requirements and health-related quality of life (HR-QOL), and reduced the risk of all-cause mortality. Budesonide/glycopyrronium/formoterol was generally well tolerated, with the tolerability profile being generally similar to that of the individual components. Budesonide/glycopyrronium/formoterol provides a useful and convenient option for the maintenance treatment of COPD, including for patients whose disease is inadequately controlled with dual ICS/LABA or LAMA/LABA therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01562-6.

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Section: Pharmacokinetic Propertiesmentioning

confidence: 99%

Budesonide/Glycopyrronium/Formoterol: A Review in COPD

Heo

2021

Drugs

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“…17 Similarly, in a study that evaluated the PK properties of budesonide/FF/GB in Chinese, Japanese, and Caucasian healthy volunteers, systemic exposure to all 3 molecules after a single 320/9.6/18-μg dose was higher in the Japanese participants: the ratio of the unadjusted geometric means for AUC 0-12 and C max was 1.32 and 1.41 for budesonide, 1.15 and 1.38 for formoterol, and 1.33 and 1.24 for GB, respectively, although with the authors concluding that the data indicated ethnic insensitivity. 18 An important finding is that plasma exposure increased with increasing dose of all 3 molecules. For B17MP, C max , AUC 0-t , and AUC 0-∞ increased approximately dose proportionally between the 2 therapeutic doses in both ethnicities, as did AUC 0-t between BDP/FF/GB 200/12/25 μg and the supratherapeutic dose, with C max and AUC 0-∞ increasing dose proportionally or slightly less.…”

Section: Discussionmentioning

confidence: 97%

Ethnic Sensitivity Study of the Extrafine, Single-Inhaler, Triple Therapy Beclomethasone Dipropionate, Formoterol Fumarate, and Glycopyrronium Bromide Pressurized Metered Dose Inhaler in Japanese and Caucasian Healthy Individuals: A Randomized, Double-Blind, Single-Dose Crossover Study

Cella

Täubel

Delestre-Levai

et al. 2021

Clinical Therapeutics

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Purpose: A number of single-inhaler, fixed-dose, triple combinations are available for the management of chronic obstructive pulmonary disease and/or asthma. One of these is the extrafine formulation beclomethasone dipropionate, formoterol fumarate, glycopyrronium bromide (BDP/FF/GB). Given that differences in ethnicity can result in differences in systemic exposure, we evaluated the relative pharmacokinetic (PK) profiles of BDP/FF/GB in Japanese vs Caucasian healthy volunteers to assess the need for dose adjustment.Methods: This randomized, double-blind, singledose, 4-way crossover study recruited healthy men and women 20 to 55 years of age; for each Japanese person a Caucasian was enrolled who matched in terms of sex, age, and weight. Study treatments included BDP/FF/GB 200/12/25 and 400/12/25 μg (therapeutic), 800/48/100 μg (supratherapeutic), and placebo. PK blood samples were taken up to 24 hours for evaluation of BDP, beclomethasone 17-monopropionate (B17MP, an active metabolite of BDP), and formoterol and up to 48 h for GB. The primary objective was to characterize the PK profiles of BDP, FF, and GB after administration of a single dose of BDP/FF/GB in Caucasian and Japanese healthy volunteers in terms of the AUC 0-t and C max of B17MP, formoterol, and GB.Findings: Of the 32 recruited participants (16 Japanese and 16 Caucasian ), 30 completed the study. A clear plasma exposure dose-response relationship was found for all 4 molecules. B17MP C max geometric mean ratios for Japanese vs Caucasian participants for the 3 study treatments ranged from 1.17 to 1.26, and AUC 0-t ratios ranged from 1.16 to 1.22; thus, the findings were comparable between the ethnicities. Formoterol exposure was higher in Japanese than Caucasian participants (C max , 1.22-1.53; AUC 0-t , 1.23-1.40). The GB C max with BDP/FF/GB 400/12/25 μg (1.09) and AUC 0-t values for all three doses (0.98-1.17) were comparable in the 2 populations, but C max with 200/12/25 and 800/48/100 μg were higher in Japanese participants (1.32 and 1.42, respectively). Pharmacodynamic (cortisol, potassium, glucose, blood pressure, heart rate, and QT interval with the Fridericia correction) and safety profile results were similar in the 2 ethnicities, with most patients not experiencing any adverse events.Implications: Exposure to BDP/FF/GB pressurized metered dose inhaler at therapeutic and supratherapeutic doses was associated with higher plasma levels in Japanese versus Caucasian healthy volunteers. These PK differences did not translate into meaningful dif-

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“…In those of Asian descent, systemic budesonide exposure did show a dose-proportional relationship between the 160- and 320-µg doses of BGFF after single and repeated dosing. 6,7 For glycopyrronium, a lower C max was observed in Chinese individuals compared to Western 7 and Japanese individuals 8 ; however, there were no observable differences in safety and efficacy because of this. A follow-up post hoc analysis of phase 1 study data further supports the determination that no appreciable differences in PK parameters exist between healthy, ethnically diverse individuals when single and repeated doses of BGFF are administered.…”

Section: Pharmacology and Pharmacokineticsmentioning

confidence: 93%

“…A follow-up post hoc analysis of phase 1 study data further supports the determination that no appreciable differences in PK parameters exist between healthy, ethnically diverse individuals when single and repeated doses of BGFF are administered. 8…”

Section: Pharmacology and Pharmacokineticsmentioning

confidence: 99%

“…The PK profile of single and repeated doses of BGFF, delivered via pressurized MDI using co-suspension technology, were evaluated in several phase 1, crossover, and parallel-group studies in healthy Western, Japanese, and Chinese individuals. [4][5][6][7][8] To establish bioequivalence, 3 single doses of BGFF MDI (320/14.4/10 µg, 160/14.4/10 µg, and 80/14.4/10 µg) were compared to a FDC of the LAMA/ LABA and ICS/LABA components. The 320 µg dose of BGFF was found to be bioequivalent to BFF, based on peak plasma drug concentration (C max ), area under the curve from time 0 to 12 hours (AUC 0-12 ), and total exposure to the drug (AUC 0-t ).…”

Section: Pharmacology and Pharmacokineticsmentioning

confidence: 99%

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Budesonide/Glycopyrrolate/Formoterol Fumarate Co-suspension Metered Dose Inhaler: A Triple Therapy for the Treatment of Chronic Obstructive Pulmonary Disease

Nigro

Sobieraj

2021

Ann Pharmacother

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Objective: To review current evidence on the use of a fixed-dose combination (FDC) of budesonide/glycopyrrolate/formoterol fumarate (BGFF) triple therapy delivered via metered dose inhaler (MDI) in patients with chronic obstructive pulmonary disease (COPD) and offer clinical practice insights. Data Sources: We used PubMed to conduct the literature search from 1946 through June 30, 2021, using budesonide, glycopyrrolate or glycopyrronium, and formoterol. Study Selection and Extraction: We included clinical trials in patients with COPD along with pharmacokinetic or pharmacodynamic studies. Data Synthesis: In all, 19 citations were included. BGFF MDI reduces the risk of exacerbations regardless of exacerbation history compared with dual bronchodilators or inhaled corticosteroid/long-acting β-agonist. Rescue inhaler use decreased, and patient-reported outcomes of symptoms and well-being improved with triple therapy. Mortality was decreased with the higher-dose BGFF MDI in comparison to dual bronchodilator therapy. Dysphonia and candidiasis were more common with BGFF MDI compared with dual bronchodilators, as was pneumonia. Relevance to Patient Care and Clinical Practice: BGFF MDI is the second FDC triple therapy approved for COPD treatment. BGFF MDI improves important patient outcomes in COPD, including exacerbation risk. The unique co-suspension technology allows delivery of 3 active ingredients in 1 inhaler, a potential benefit to overcome adherence and technique-related barriers. These benefits must be gently weighed against the increased risk of pneumonia. Conclusion: The findings from phase 3 trials support the efficacy and safety of triple therapy in COPD. Future studies are needed to confirm potential mortality benefit and the role of triple therapy in patients without an exacerbation history.

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Ethnic pharmacokinetic comparison of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) between Asian and Western healthy subjects

Cited by 3 publications

References 25 publications

Budesonide/Glycopyrronium/Formoterol: A Review in COPD

Budesonide/Glycopyrronium/Formoterol: A Review in COPD

Ethnic Sensitivity Study of the Extrafine, Single-Inhaler, Triple Therapy Beclomethasone Dipropionate, Formoterol Fumarate, and Glycopyrronium Bromide Pressurized Metered Dose Inhaler in Japanese and Caucasian Healthy Individuals: A Randomized, Double-Blind, Single-Dose Crossover Study

Budesonide/Glycopyrrolate/Formoterol Fumarate Co-suspension Metered Dose Inhaler: A Triple Therapy for the Treatment of Chronic Obstructive Pulmonary Disease

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