Pulmatrix Announces Positive Top-Line Results from Parts 1 and 2 of the 3-Part Phase 1/1b Clinical Trial of Pulmazole - an Inhaled Dry-Powder iSPERSE™ Formulation of Itraconazole
All doses were well tolerated in normal healthy volunteers in Parts 1 and 2 at up to 35 mg of itraconazole, the maximal dose planned
Substantially lower systemic exposure (100- to 400-fold) was observed in Pulmazole cohorts versus levels reported with oral Sporanox
All objectives from Parts 1 and 2 successfully met
LEXINGTON, Mass., June 25, 2018 /PRNewswire/ -- Pulmatrix, Inc. (NASDAQ: PULM), a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary diseases announced today top-line results for the ongoing first-in-human study for 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 well tolerated across all doses tested in all cohorts in Parts 1 and 2. Additionally, summary data for systemic pharmacokinetics from Part 2 following 14 days of daily inhalation of Pulmazole at doses ranging between 10 and 35 mg inhaled itraconazole suggest that total systemic exposure over 24 hours (AUC0-24h) is approximately 100- to 400-fold lower that what would be expected following administration of 200 mg of oral Sporanox. These results support the potential of Pulmazole to improve the safety profile of oral Sporanox, as there is a progressive increase in the probability of toxicity occurring with increasing concentrations of itraconazole after oral administration.
"The trial results suggest that inhalation of itraconazole can be safe and well tolerated and may be a better approach to treating ABPA, a disease for which there are no currently approved therapies," said Robert W. Clarke, Ph.D., Chief Executive Officer of Pulmatrix. "The reduced systemic exposure combined with the safety and tolerability profile observed supports the feasibility and potential differentiated benefits associated with this route of administration to treat aspergillus-related diseases in the lungs."
The Phase 1/1b study included 58 patients in a 3-part open-label study in healthy adults (Parts 1 and 2) and in adults with mild to moderate, stable asthma (Part 3). The main objectives of Part 1 single ascending dose and Part 2 multiple ascending dose was to evaluate the safety, tolerability, and pharmacokinetics (PK) of Pulmazole administered as either single- or multiple- doses administered daily over 14 days in normal healthy volunteers. The maximum dose of Pulmazole planned to be administered in this study was 35 mg itraconazole (70 mg dry powder including excipients). A total of 23 subjects were dosed across 4 cohorts (5 mg, 10 mg, 25 mg, and 35 mg itraconazole) in Part 1, and a total of 18 subjects were dosed across 3 cohorts (10 mg, 20 mg, and 35 mg itraconazole) in Part 2.
Results from Part 1 and Part 2 of the study demonstrated 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 adverse event was the infrequent occurrence of a mild cough. Pharmacokinetic analysis of plasma showed that following dosing with Pulmazole, systemic drug levels were 100- to 400-fold lower than historically reported levels following dosing of oral Sporanox at the currently prescribed dose.
All subjects in Part 3 have completed their study visits and analysis of the preliminary data is underway and expected to be complete in mid-July 2018.
Jim Roach, MD, Chief Medical Officer of Pulmatrix remarked, "We are extremely pleased that upon review of the preliminary results from the normal healthy volunteer component of the study, Pulmazole was well tolerated up to the maximum dose tested. Additionally, the substantially lower systemic exposure for itraconazole following inhaled administration speaks to the potential for Pulmazole to improve upon the known safety concerns associated with oral Sporanox. We look forward to further reviewing and reporting the data from Part 3 of the study in asthmatic subjects, which included measuring itraconazole in sputum to assess relative lung exposure following administration of either oral Sporanox or Pulmazole, in the next few weeks."
SOURCE Pulmatrix, Inc.