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Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir® Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies

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Abstract

Background and Objective

Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir® hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI.

Methods

Two double-blind, randomized, double-dummy, crossover, multicenter, placebo-controlled studies in persistent asthma patients were conducted. Study 1: 47 adult patients were treated with cumulative doses of albuterol mDPI or ProAir HFA (90 µg/inhalation; 1 + 1 + 2 + 4 + 8 inhalations) or placebo. Study 2: 71 patients aged ≥12 years were randomly assigned to receive 90 or 180 μg of albuterol mDPI or ProAir HFA, or placebo. Primary efficacy endpoints were baseline-adjusted forced expiratory volume in 1 s (FEV1) at 30 min (30-min FEV1) after each cumulative dose (Study 1) and FEV1 area under the effect curve over 6 h (FEV1 AUEC0–6) after dosing (Study 2).

Results

Study 1: differences, with corresponding 90 % confidence intervals, between albuterol mDPI and ProAir HFA in FEV1 after each cumulative dose and in FEV1 AUEC0–6 after the final dose were within pre-established equivalence limits. The difference in FEV1 at high vs. low doses was significant for both active treatments (p < 0.0001). Active treatments were similar in systemic exposure, extrapulmonary pharmacodynamics, and safety. Study 2: mean FEV1 AUEC0–6 was significantly greater than for placebo for both doses of albuterol mDPI and ProAir HFA (p < 0.0001). Albuterol mDPI was comparable to ProAir HFA at 90 and 180 µg. Both study treatments were generally well tolerated.

Conclusion

The bronchodilatory efficacy and pharmacokinetic/pharmacodynamic profiles of albuterol mDPI and ProAir HFA are comparable, with a safety profile consistent with that of inhaled albuterol.

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Acknowledgments

The authors acknowledge and thank the investigators from Study 1 and Study 2 and their respective teams for their valuable contributions during the conduct of this study.

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Authors and Affiliations

  1. Clinical Research Institute of Southern Oregon, PC, 3860 Crater Lake Avenue, Suite B, Medford, OR, 97507, USA

    Edward M. Kerwin

  2. Teva Branded Pharmaceuticals R&D Inc., Frazer, PA, USA

    Herminia Taveras, Harald Iverson, Denise Wayne & Tushar Shah

  3. Maple Glen, PA, USA

    Mark S. Lepore

  4. Northeast Medical Research Associates, North Dartmouth, MA, USA

    David S. Miller

Authors
  1. Edward M. Kerwin
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  2. Herminia Taveras
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  3. Harald Iverson
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  4. Denise Wayne
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  5. Tushar Shah
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  6. Mark S. Lepore
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  7. David S. Miller
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Corresponding author

Correspondence to Edward M. Kerwin.

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Funding

This study was sponsored by Teva Branded Pharmaceutical Products R&D, Inc. Medical writing and editorial assistance during the preparation of this manuscript was provided by ApotheCom, with funding provided by Teva.

Conflicts of interest

Dr. Kerwin has served on advisory boards for Amphastar, AstraZeneca (Pearl), Mylan, Novartis, Sunovion, and Theravance; participated on speaker panels for Amphastar, AstraZeneca (Pearl), Boehringer Ingelheim, Forest, Mylan, Novartis, Sunovion, and Theravance; and has received travel reimbursement for presentations at meetings from Forest, Novartis, and Teva. He has conducted multicenter clinical research trials for approximately 40 pharmaceutical companies. Dr. Miller receives research funding from Teva and served as principal investigator for Teva through Northeast Medical Research Associates. Drs. Iverson, Shah, Taveras, and Wayne are employed by Teva Branded Pharmaceutical Products R&D and may hold stock or stock options in Teva. Dr. Lepore was employed by Teva Branded Pharmaceutical Products R&D at the time the study was conducted and holds stock or stock options in Lupin Inc.

Ethical approval

All procedures in both studies were conducted in accordance with the ethical principles based on the 1964 Declaration of Helsinki (and its amendments) and Good Clinical Practice. Both studies were approved by the institutional review board at each study site.

Informed consent

All patients from both studies provided written informed consent before screening.

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Kerwin, E.M., Taveras, H., Iverson, H. et al. Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir® Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies. Clin Drug Investig 36, 55–65 (2016). https://doi.org/10.1007/s40261-015-0346-y

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  • DOI: https://doi.org/10.1007/s40261-015-0346-y

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