A Phase I study of inhaled PB01 in healthy male volunteers to assess the anti-inflammatory effects of PB01 on lung inflammation.

INTERVENTION: PB01 solution for oral inhalation is administered using a nebuliser and consists of PB01 in 20mM sodium phosphate buffer and 500mM sodium chloride, pH7. A randomised, double blind, placebo‐controlled, two period crossover study in healthy male participants. Over the two Treatment Periods, all participants will be randomised to receive a single orally inhaled dose of either 30mg PB01 or Placebo (in either sequence) at each Treatment Period. Investigational Medicinal Product (IMP) will be administered by an Aerogen Aeroneb Go vibrating mesh nebuliser for a duration of 15 minutes. Participants will be trained on the use of the Aeroneb Go nebuliser. An inhaled lipopolysaccharide (LPS) challenge (30 microgram) will be administered 1 hour post commencement of the IMP dose administration. The total dose of 30 microgram LPS (from Escherichia coli 026:B6 (Sigma)) will be delivered by a total of 5 inhalations using a calibrated breath activated nebuliser. Following Screening, eligible participants will be admitted to the study unit on Treatment Period 1 Day 1 and will be randomised in a 1:1 ratio to receive either PB01 followed by Placebo or Placebo followed by PB01 in a two period crossover design. IMP will be administered on Treatment Period 1 Day 1 followed by the LPS challenge. Administration of the IMP and LPS will be performed at the study unit under the supervision of the clinical site personnel and participants will be confined to the study unit overnight (i.e. 24 hours) and discharged from the study unit after completion of all study procedures on Treatment Period 1 Day 2. There will be a minimum of 24 days and a maximum of 65 days wash‐out between dosing on Treatment Period 1 Day 1 and Treatment Period 2 Day 1. At least 72 hrs and no more than 10 days prior to Treatment Period 2 Day 1 participants will attend a Baseline Visit which will include sputum sampling to determine eligibility to continue to Treatment Period 2. On Treatment Period 2 Day 1, participants will be admitted to the study unit for IMP administration followed by the LPS challenge under the supervision of the clinical site personnel and participants will be confined to the study unit overnight (i.e. 24 hours) and discharged from the study unit after completion of all study procedures on Treatment Period 2 Day 2. An End of Study visit will be performed 7 days (+ 5 days) after the last dose of IMP (i.e on Day 8 (+5)). The maximum planned study duration will be 99 days per participant. The investigator is responsible for maintaining accurate IMP accountability records throughout the study. Drug accountability will be performed by the monitor during monitoring visits to reconcile the number of IMP vials dispensed with that used/returned. CONDITION: Airway inflammation and fibrosis PRIMARY OUTCOME: Change in neutrophil content of an induced sputum sample collected 6 hours post LPS challenge compared with the baseline neutrophil content of an induced sputum sample collected at least 72 hours prior to dosing with IMP. SECONDARY OUTCOME: Change in serum levels of C‐reactive protein. Changes in blood inflammatory cell counts (neutrophils, monocytes, eosinophils). Changes in sputum inflammatory cell counts (total cells, macrophages, eosinophils). Sputum concentrations of PB01 measured at 7 hours post commencement of PB01 dose administration. To evaluate the safety and tolerability of orally inhaled PB01 in healthy male participants. INCLUSION CRITERIA: Able to speak, read and understand English sufficiently to understand the purposes and risks of the study and to provide written informed consent. Healthy males aged 18 to 55 years inclusive at the time of consent. Body Mass Index (BMI) of greater than or equal to 18 to less than or equal to 32.0 kg/m2. Normal pulmonary function and performance on pulmonary function tests, defined as Forced expiratory volume measured in one second, expressed in litres (FEV1), and Forced vital capacity, expressed in litres (FVC) both greater than or equal to 80% of their predicted value for age, ethnicity, sex and height. Participants must be willing and able to comply with scheduled visits, study restrictions, treatment plan, laboratory tests and other study procedures. Participants must be willing not to donate sperm and to comply with the medically acceptable contraceptive requirements of the study from first dose of IMP to 30 days afte