Pulmatrix, a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary diseases announced that the single dose escalation phase of the first-in-human study for Pulmazole (PUR1900) - an inhaled iSPERSE formulation of the anti-fungal drug itraconazole for the treatment of allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma - has commenced.  

ABPA is a disease that occurs most often in patients with underlying asthma or cystic fibrosis, and it is characterized by an exaggerated allergic hypersensitivity response of the immune system to the fungus Aspergillus growing in the airways. Oral itraconazole (Sporanox) is currently used as an adjunctive treatment to corticosteroids in ABPA patients. However, its use is limited by poor bioavailability, variable pharmacokinetics, and toxicity concerns related primarily to the risk of gastrointestinal and cardiac side effects, as well as extensive drug-drug interactions.  The Pulmatrix Pulmazole program is the first inhaled dry powder version of itraconazole known to the company to be advanced into clinical development, with the goal of improving upon the known safety and efficacy profile associated with oral Sporanox by delivering the drug directly to the lung.

This phase 1/1b study is being conducted in healthy subjects and patients with mild to moderate stable asthma.  The study will include single ascending dose (SAD) and multiple ascending dose (MAD) arms in normal healthy volunteers (NHV) to assess safety, tolerability, and pharmacokinetics (PK). A third study arm will evaluate safety and tolerability in patients with mild to moderate stable asthma and will also include PK analysis of itraconazole levels in the blood and sputum following administration of a single dose of oral itraconazole (Sporanox; 200 mg itraconazole) or Pulmazole (20 mg itraconazole) in a crossover study design.

"Dosing our first subject with Pulmazole and entering the clinic represents a major milestone for this program commented Jim Roach, M.D., chief medical officer of Pulmatrix.  In addition to generating the requisite safety and tolerability data from this study to advance dosing of Pulmazole into asthmatic patients with ABPA, we anticipate that the collective pharmacokinetic data obtained in Phase 1 will further corroborate the key PK preclinical findings reported last week at the 8th Advances Against Aspergillosis Conference in Lisbon, Portugal - namely, that Pulmazole can provide higher lung exposure and lower systemic exposure than oral Sporanox."

The study is planned to include up to 42 subjects in the SAD/MAD evaluation in NHV and 16 asthmatics in the crossover study. The company expects that top line results will be available in mid-2018.

Robert Clarke, Ph.D., chief executive officer of Pulmatrix, added "The initiation of our Pulmazole clinical trial is important validation of our iSPERSE dry powder technology as the second program to advance into the clinic along with PUR0200.  We look forward to advancing Pulmazole and our iSPERSE pipeline to improve the treatment approaches for patients with unmet medical needs."