An inhaled PDGF receptor inhibitor for the treatment of pulmonary arterial hypertension

点击翻译按钮获取中文摘要

 DESCRIPTION (provided by applicant): Pulmokine is developing a novel inhaled PDGF receptor (PDGFR) kinase inhibitor, PK10571 as a treatment for Pulmonary Arterial Hypertension (PAH). The purpose of this Phase IIB Small Market Bridge Award is to progress PK10571 through a phase 1A clinical trial for safety. PAH is an orphan disease with high morbidity and mortality despite currently available treatments. Pulmokine's current Phase II SBIR grant was designed to develop the formulation for inhalation of the API, determine pharmacokinetics, and maximum tolerated dose in the rat. These studies have been accomplished, and set the stage for IND enabling studies. The IND enabling studies will consist of in vivo animal toxicology studies in two species (rat and dog) as required by the FDA. These studies are currently funded separately through a Stage B VITA contract awarded to Pulmokine through the NHLBI. The phase IIB small market award will provide the means to perform a phase 1A first in human exposure clinical trial in healthy volunteers and to perform longer term toxicology studies. After completion of the Phase 1A clinical trial a combined phase 1B/2A clinical trial in patients with PAH will be performed with investor funds. The primary endpoint of the phase 1B/2A trial will be safety, with efficacy as a secondary endpoint. After completion of the phase 1B/2A trial, Pulmokine will form a strategic alliance or partnership with a larger pharmaceutical company (or undergo acquisition). Such an alliance will allow performance of a phase III clinical trial and commercialization of our drug product as a treatment for PAH. The part of the project that will be funded by this phase IIB award includes the following: 1) Performance of a phase 1A safety study of dry powder inhaled PK10571 in healthy human volunteers. This phase 1A clinical trial will consist of a blinded single ascending dose (SAD) placebo controlled protocol followed by a multiple dose ascending (MAD) placebo controlled protocol. All of the key components are in place to perform this first in human clinical trial: 1) cGMP manufacturer of of the API (IRIX Pharmaceuticals) ; 2) cGMP manufacture of spray dry powder formulation (BEND Research Inc.); 3) the Clinical site for Performance: (Parexel Phase 1 Unit). 2) Performance of a 6 month GLP toxicology study in the rat. This study is necessary per ICH M3(R2) guidelines before initiation of the longer phase 2 clinical trial. ICH guidelines recommend toxicology studies of the same length as the clinical trial for trials of 3-6 months duration. Since the Phase 1B/2A trial is planned for six months, we will need the 6 month rat GLP tox study.