Pulmatrix Announces Positive Top-Line Preliminary Results from Part 3 of the 3-Part Phase 1/1b Clinical Trial of Pulmazole - an Inhaled Dry-Powder iSPERSE™ Formulation of Itraconazole
Single dose of Pulmazole safe and well tolerated in subjects with asthma
PK analysis of sputum samples demonstrated ~50-fold higher lung exposure following inhalation of Pulmazole compared to oral Sporanox® despite inhaling only one tenth the dose of itraconazole (20 mg) contained in a dose of oral Sporanox (200 mg)
Total systemic exposure was ~85-fold lower following inhalation of 20 mg Pulmazole compared to 200 mg of oral Sporanox
All objectives from Part 3 successfully met, on track to initiate a Phase 2 study in asthmatic patients with allergic bronchopulmonary aspergillosis (ABPA) in 2018
LEXINGTON, Mass., July 17, 2018 /PRNewswire/ -- Pulmatrix, Inc. (NASDAQ: PULM) announced today that all dosing and follow up visits have been completed for Part 3 of the ongoing first-in-human study of Pulmazole (PUR1900) - an inhaled iSPERSETM formulation of the anti-fungal drug itraconazole for the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma. Pulmazole was safe and well tolerated administered as a single-dose of 20 mg inhaled itraconazole in asthmatic subjects. Based on review of the top-line preliminary data, the study successfully achieved all objectives. The company previously reported positive top line data from Part 1 and 2 of the study in normal healthy volunteers. With these encouraging Phase 1/1b results from Part 3 now also in hand, Pulmatrix plans to initiate a Phase 2 trial in ABPA patients in Q4 2018.
In the pharmacokinetic analysis of the data available, maximum sputum itraconazole concentrations were approximately 50-fold higher following inhalation dosing of 20 mg of Pulmazole compared to oral Sporanox dosing of 200 mg. Additionally, high lung exposure following inhalation of a single dose of 20 mg Pulmazole was maintained over a 24-hour period, whereas sputum concentrations of itraconazole decreased between 2 hours and 6 hours after a single 200 mg oral Sporanox dose. Following inhalation of 20 mg of Pulmazole, total systemic exposure over 24 hours (AUC0-24h) and maximum plasma concentration (Cmax) were approximately 85-fold and 250-fold lower compared to AUC0-24h and Cmax following 200 mg of oral Sporanox, respectively.
Dave Singh, MD, Professor of Clinical Pharmacology and Respiratory Medicine at the University of Manchester and principal investigator on Part 3 of the study commented, "These data in asthmatics are very promising regarding the future potential of Pulmazole as a therapy for patients with ABPA, a disease with significant unmet medical need. Demonstration of significantly higher levels in the lung as well as significantly lower systemic exposure following inhalation of Pulmazole suggests that Pulmazole has the potential to dramatically improve upon the known safety and efficacy of Sporanox."
The main objectives of the study in Part 3 were to evaluate the safety, tolerability, and pharmacokinetics of Pulmazole administered as a single-dose in mild-to-moderate asthmatics. Subjects were administered either a single dose of oral itraconazole (Sporanox; 200 mg itraconazole) or Pulmazole (20 mg itraconazole) in a crossover study design, to compare relative levels of itraconazole in both the blood and sputum after being administered by either route.
Part 3 of the study was planned to include 16 asthmatic subjects. A total of 17 asthmatic subjects (including one replacement subject) were dosed. The preliminary data reviewed suggests that Pulmazole was safe and well tolerated. All study drug-related adverse events (AEs) were characterized as mild, and no moderate, severe or serious study drug-related AEs were reported. The most common AEs in Part 3 following administration of Pulmazole were mild and transient headache, and the infrequent occurrence of a mild cough.
"These preliminary safety, tolerability and pharmacokinetic results from Part 3 in subjects with asthma strongly corroborate and further extend the positive findings we observed in normal healthy volunteers," commented Jim Roach, MD, Chief Medical Officer of Pulmatrix. "Notably, itraconazole levels in the sputum of asthmatic subjects were much higher following inhaled versus oral administration, despite administering much lower doses of itraconazole via the inhaled route. This further supports the potential of Pulmazole to improve upon the efficacy observed with oral Sporanox in patients with ABPA. We believe we have now generated the requisite data to advance to initiation of a Phase 2 study in patients with asthma and ABPA and are planning for study initiation in the fourth quarter of this year. We look forward to submitting the Phase 1/1b study results in the next several weeks for presentation at a major scientific conference later this year."
SOURCE Pulmatrix, Inc.