Pulmatrix, a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary diseases, has received authorization of its Clinical Trial Application from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) to initiate its 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.
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.
This phase 1/1b study will be 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. This program represents the first inhaled dry-powder formulation of itraconazole that the Company is aware of to enter clinical development.
"We have begun to screen subjects and look forward to initiating dosing in our first clinical trial for Pulmazole in early February," commented James Roach, M.D., chief medical officer of Pulmatrix. "There is a significant unmet medical need in patients with both asthma and ABPA, and we believe that by delivering higher doses of itraconazole directly to the lungs while minimizing systemic exposure, Pulmazole has the potential to provide significant advantages in both efficacy and safety relative to oral itraconazole."
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 approval to initiate clinical dosing of Pulmazole is an important step for Pulmatrix in 2018. We expect an ambitious year advancing development of both Pulmazole and PUR1800 as part of our core company strategy, while continuing progress on our US partnership of the PUR0200 once daily bronchodilator program with Vectura."