A two-part, open-label study to assess the pharmacokinetics, pharmacodynamics and safety of single doses of inhaled and intravenously administered D,L lysine acetylsalicylate • glycine (LASAG) in healthy adult subjects: Study Part A follows a randomized, cross-over design to compare three dose levels of inhaled LASAG to one dose level of intravenously administered LASAG and Study Part B follows a single group design to investigate a XXXXX LASAG inhalation solution.

Prior treatment

• Positive test for alcohol, drugs or cotinine.
• Use of any concomitant medication or any drugs / medicines (including dietary supplements, natural and herbal remedies) within 14 days or 10 times their elimination half-life, whichever is longer, prior to the first study treatment administration. Allowed treatments are the use of contraceptives (as detailed in Appendix 2) and hormonal replacement therapy if the female subject has been on stable treatment for at least 3 months and continues treatment throughout the study. Also, the occasional use of paracetamol up to 2 g/day is permitted.
• Use of any investigational drug or participation in any clinical study within 30 days or 10 elimination half-lives of the study drug administered in a previous study, whichever is longer, prior to the expected date of first administration of study treatment.
• Previous randomization, respectively assignment, to study treatment in this study.
• History of drug or alcohol abuse within 6 months prior to screening.
• Excessive consumption of caffeine- or xanthine-containing products (>5 cups of coffee a day or equivalent) or inability to stop consuming from 48 hours prior to study treatment administration.
• Consumption of resveratrol-containing products or products with enzyme-inducing or enzyme-inhibiting properties (for details refer to Section 5.3.1) within 14 days prior to first study treatment administration.
• Consumption of poppy seeds within 72 hours prior to first study treatment administration.
• Any significant blood loss or donation of more than 450 mL of blood / blood products or having been transfused any blood or blood products within 30 days prior to first study treatment administration.
• Chronic or acute viral, bacterial, or fungal airway infections, including laryngeal infections, mouth and throat infections and hoarseness, within 2 weeks prior to screening.
• Other clinically relevant chronic or acute infectious illness or febrile illness within 2 weeks prior to screening.

Other illness

• Any history or evidence of any clinically relevant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinologic, hematologic, immunologic, metabolic, genitourinary, pulmonary, neurologic, dermatologic, musculoskeletal, psychiatric and/or other major disease or malignancy as determined by medical evaluation capable of significantly altering the absorption, metabolism, or elimination of drugs, constituting a risk when taking the study treatment or interfering with the interpretation of data.
• Tendency for vasovagal reactions (e.g., after venipuncture) or history of syncope.
• Evidence of COVID-19 signs or symptoms or confirmed COVID-19 infection within the last 2 weeks.
• Thyroid disorders as evidenced by thyroid-stimulating hormone outside normal range and confirmed by free triiodothyronine and free thyroxine outside normal range. (Subjects with suspected compensated thyroid hormone formation disorders as indicated by thyroid-stimulating hormone outside normal range but free triiodothyronine and free thyroxine within normal range may be included at the discretion of the Investigator).
• Positive test for hepatitis B surface antigen, hepatitis C virus antibodies and anti-human immunodeficiency virus (HIV) antibodies (anti-HIV 1+2) and HIV p24 antigen.
• Any clinically relevant history of allergic conditions, also including relevant seasonal allergies or allergies to any other drugs.
• History of any surgery of the gastrointestinal or respiratory tract which might interfere with drug absorption from any of both organ systems or with regular drug distribution and deposition in the airways (excluding minor abdominal surgery without significant tissue resection, e.g., appendectomy and herniotomy).
• Any other conditions or factors which in the opinion of the Investigator may interfere with study conduct.
• Known or suspected hypersensitivity to acetylsalicylic acid, lysine, or glycine.
• Contraindications for the use of the study treatments, such as hypersensitivity to LASAG or other salicylates or a history of asthma or other allergic reactions induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory drugs, history of peptic ulcers or hemorrhagic conditions, renal or hepatic impairment, anamnesis of gout or relevantly elevated urate levels.
• Suspicion of bleeding diathesis, e.g., also including epistaxis or hemorrhoids/anal fissures with bleeding tendency.

Lab values

• Clinically relevant abnormality (excluding minor excursions from normal ranges) following the Investigator’s review of the physical examination, ECG, lung function and clinical study laboratory tests that, in the opinion of the Investigator, would preclude inclusion in the study.
• ECG with clinically relevant abnormality or showing a QT interval frequency-corrected according to Fridericia’s formula (QTcF) >450 ms for male and >470 ms for female subjects, PR >215 ms, or QRS >120 ms.
• Elevations in alanine aminotransferase ≥1.1 x upper limit of normal (ULN), aspartate aminotransferase ≥1.2 x ULN, serum bilirubin ≥1.2 x ULN or creatinine ≥1.1 x ULN.
• Known glucose-6-phosphate dehydrogenase deficiency.

Other

• Supine systolic blood pressure >140 mmHg or <90 mmHg; diastolic blood pressure >90 mmHg or <50 mmHg and pulse rate <50 bpm or >90 bpm after at least 5 minutes rest in supine position and body temperature of <35.9 and >37.6°C.
• Thrombocytes in blood < 150 per nL.
• Positive test for SARS-CoV-2.
• Positive pregnancy test in female subjects.
• Higher than low-risk alcohol consumption i.e., average weekly alcohol intake of >14 units/week for men (daily dose of 24 g, weekly dose of 168 g) and 7 units/week for women (daily dose of 12 g, weekly dose of 84 g). One unit (12 g) corresponds to 0.3 L of beer/day or 0.12 L of wine/day or 1 glass (at 2 cL) of spirits/day.
• Following a vegetarian, vegan, or restricted diet (e.g., gluten-free) or not willing or able to eat the meals provided.
• Strenuous physical activity within 72 h before admission.
• Employee of the Sponsor, the Nuvisan Group, or other Contract Research Organization involved in the clinical study.
• Legal incapacity or limited legal capacity, or incarceration.
• Inability to understand or communicate reliably with the Investigator or considered by the Investigator to be unable to or unlikely to co-operate with the protocol requirements, instructions, and study-related restrictions.
• Inability to understand the full nature and purpose of the study, including possible risks and adverse effects.

• Age of 18 to 55 years inclusive, at the time of signing the informed consent.
• Provision of written informed consent as described in Appendix 1 prior to any clinical study specific procedure.
• Able to demonstrate correct inhaler use after training at screening.
• Body weight ≥ 50 kg at screening.
• Body mass index (BMI) within the range 20.0 to 29.9 kg/m2 (inclusive) at screening.
• Male or female.
• A male subject must agree to the following from the signing of the informed consent form (ICF) until 90 days after the last study treatment administration: i. Refrain from donating sperm. AND ii. Use a highly effective contraceptive method (failure rate < 1% per year) as detailed in Appendix 2 of the CSP together with a barrier method if engaging in penile-vaginal intercourse with a female partner of childbearing potential, respectively use a male condom when having penile-vaginal intercourse with a pregnant or breastfeeding partner.
• A female subject is eligible to participate if she is neither pregnant nor breastfeeding and the following applies: i. Subject is not a woman of childbearing potential (WOCBP), meaning that subject is surgically sterilized or postmenopausal as defined in Appendix 2. OR ii. A WOCBP must agree to use highly effective contraception as detailed in Table 8 (Appendix 2) starting at least 90 days before the first study treatment administration and throughout the clinical study period until 90 days after last study treatment administration. Additionally, a barrier method must be used from screening onwards. The subject should be informed of the potential risks associated with becoming pregnant while enrolled in a clinical study.
• Overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, ECG, and laboratory tests.
• Forced expiratory volume in 1 second (FEV1) > 80% of predicted value.
• Non-smoker for at least 30 days before screening. Subjects must also have abstained from the use of other nicotine-containing products (e.g., nicotine patch, chewing gum or e cigarettes) for at least 30 days before screening.