A First-in-Human Study to Assess the Safety and Tolerability of PDNO

Exclusion Criteria

• •History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, might interfere with the drug absorption, distribution, metabolism or excretion of the drug or influence the results or the subject's ability to participate in the study
• •Any clinically significant illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP
• •Malignancy within the past 5 years
• •Any planned major surgery within the duration of the study
• •Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV)
• •Women who are pregnant or who are breast feeding
• •Known patent foramen ovale or other cardiac phenomenon putting the subject at risk in the study
• •Presence of history of Raynaud Syndrome
• •After 10 minutes supine rest at the time of screening, any vital sign values outside the following ranges: Systolic blood pressure \<90 or \>140 mmHg, or Diastolic blood pressure \<50 or \>90 mmHg, or Pulse \<40 or \>90 bpm
• •Prolonged QTcF (\>450 ms), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator
• •Known history of migraine or frequent headache of other genesis (in average \>1 episode of grade 2 (CTCAE v5.0, headache per week)
• •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to PDNO
• •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity to the local anaesthesia planned to be used in the study
• •Known hypersensitivity to propanediol
• •Veins unsuitable for CVC and arterial cannula insertion
• •Failure to perform the FeNO measurement at screening
• •FeNO level ≥ 30 ppb
• •Within 1 month prior to Screening received continuous treatment with non-steroidal anti-inflammatory drugs (NSAIDs), novel oral anticoagulants (NOACs), warfarin, clopidogrel, or acetylsalicylic acid
• •Regular use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals within 2 weeks prior to the (first) administration of IMP
• •Planned treatment or treatment with another investigational drug within 3 months prior to Day -1
• •Current smokers or users of nicotine products
• •Positive screen for drugs of abuse or alcohol
• •Presence or history of alcohol abuse or excessive intake of alcohol
• •Presence or history of drug abuse, as judged by the Investigator
• •History of, or current use of, anabolic steroids
• •Excessive caffeine consumption defined by a daily intake of \>5 cups of caffeine containing beverages
• •Intake of xanthine and/or taurine containing energy drinks at the day of screening.
• •Plasma donation within one month of screening or blood donation
• •Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements
• •Previous confirmed COVID-19 that required hospitalisation
• •Signs or symptoms probably consistent with COVID-19 disease within the last 7 days prior to Visit 2 or close contact with confirmed COVID-19 patient within the last 7 days prior to Visit 2, as judged by the Investigator
• •Positive result for ongoing SARS-CoV-2 presented at Visit 2