Improved bioavailability of cromolyn sodium using inhaled PA101 delivered via eFlow® nebulizer

ABSTRACT

In 1960s, cromolyn sodium (CS) has been introduced as the first non-steroidal anti-inflammatory drug for the treatment of allergic and mast-cell driven diseases. Its applicability has been limited due to a poor bioavailability. Here we present pharmacokinetic data of a novel high concentration formulation of CS (PA101) delivered via a high-efficiency nebulizer (eFlow®) in healthy volunteers (HVs), allergic asthmatics and patients with indolent systemic mastocytosis (ISM). In HVs, PA101 40 mg and 80 mg (30 L) and PA101 40 mg (40 L), Intal^TM (via LC® Plus) 20 mg and Nalcrom® (oral suspension) 200 mg showed maximum measured plasma concentration (C_max) of 156, 236, 88.6, 17.8 and 5.23 ng/mL, respectively, with respective areas under the plasma time-concentration curve (AUC) of 338, 526, 212, 40.6 and 33.3 h·ng/mL. Systemic exposure (AUC) to CS with PA101 40 mg was approximately 8-fold and 11-fold higher compared to Intal^TM and Nalcrom® in HVs, respectively. PA101 via eFlow® yielded comparable PK profiles in HVs and patients. Systemic bioavailability of PA101 was approximately 25% compared to approximately 1% for Nalcrom® and approximately 10% for Intal^TM, respectively. These data warrant further research on the therapeutic potential of PA101 (via eFlow®) in allergic and mast-cell driven diseases.

KEYWORDS:

• Cromolyn sodium
• eFlow® device
• safety
• pharmacokinetics
• bioavailability
• phase 1 study
• asthma
• mastocytosis

Acknowledgments

The authors would like to thank all investigators and staff of the study centre involved in the studies for their effort in conducting these clinical trials.

Disclosure statement

The authors declare the following conflict of interest in relation to this work; K.A-E. and Z.D. are employees of QPS-Netherlands B.V., which received funding for the study conduct from Patara Pharma LLC, manufacturer of PA101 and various pharmaceutical companies for execution of phase 1 and 2 clinical trials. ZD report honoraria, consultancy and speaker fees from Astrazeneca, ALK, Aquilon, Boehringer Ingelheim, CSL, HAL Allergy, MSD, Sanofi-Genzyme. H.O-E is an employee of University Medical Centre Groningen, which received consultancy fees from Patara Pharma LLC for the study conduct. H.O-E report grants and personal fees for speaking from ALK-Abello, Novartis, MEDA pharma, and Chiesi and has received fees for organizing education from Novartis, MEDA Pharma, Mead Johnson, Chiesi, Sanofi and ALK-Abello and fees for consulting from Patara and BluePrint.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was funded by Patara Pharma LLC. San Diego, California, USA.

Notes on contributors

Khalid Abd-Elaziz

Khalid Abd-Elaziz clinical pharmacologist, associate medical director and clinical safety officer QPS-Netherlands.

Hanneke Oude Elberink

Hanneke Oude Elberink Allergist - Internist (Internist-allergologist) at University Medical Center Groningen.

Zuzana Diamant

Zuzana Diamant Professor Respiratory Allergy Research, Pulmonologist/Clin Pharmacologist, Phase 0-II studies, Netherlands.