Safety, Tolerability, and Pharmacokinetics After a Single Dose of Orally Inhaled DNAzyme Solution for Nebulisation in Male Patients With Asthma

Exclusion Criteria

• •Presence of clinically significant diseases other than asthma or atopic diseases (cardiovascular, renal, hepatic, gastrointestinal, hematological, neurological, genitourinary, autoimmune, endocrine, metabolic, etc), which, in the opinion of the investigator, may either put the patient at risk because of participation in the trial, or diseases which may influence the results of the study or the patient's ability to take part in it.
• •Presence of relevant pulmonary diseases or history of thoracic surgery, such as:
• •* Known active tuberculosis
• •* Non-small cell lung cancer
• •* Pulmonary arterial hypertension
• •* History of interstitial lung or pulmonary thromboembolic disease
• •* Pulmonary resection during the past 12 months
• •* History of allergic asthma
• •* History of bronchiectasis secondary to respiratory diseases (e.g., cystic fibrosis, Kartagener's syndrome, etc.)
• •* History of chronic bronchitis, emphysema, allergic bronchopulmonary aspergillosis or respiratory infection within the 4 preceding weeks of the first morning IMP administration
• •Any absolute or relative contraindications for methacholine challenge: e.g., severe or moderate airflow limitation (FEV1 \<60% predicted or \<1.5 L), heart attack or stroke in the last 3 months, uncontrolled hypertension, known aortic aneurysm, current use of cholinesterase inhibitor medication.
• •Hospitalisation or emergency room treatment for acute asthma in the 3 months prior to screening, between screening and the start of the treatment period.
• •Intubation (ever) or hospitalisation for longer than 24 hours for the management of an asthma exacerbation within the preceding 3 months of the screening visit.
• •History of allergic reactions to any active or inactive ingredients of the nebuliser solution.
• •ECG abnormalities of clinical relevance (e.g., QTc according to Bazett's \>440 ms, PR ≥210 ms; or QRS ≥120 ms).
• •Patients with a resting heart rate \<45 bpm and \>90 bpm, systolic blood pressure \<100 mmHg and \>140 mmHg, diastolic blood pressure \<60 mmHg and \>90 mmHg.
• •Proneness to orthostatic dysregulation, fainting, or blackouts.
• •History or presence of any malignancy except for basalioma.
• •Clinically relevant abnormalities in clinical chemical, haematological or in any other laboratory variables.
• •Chronic or clinically relevant acute infections.
• •Positive results in any of the following virology tests: Hepatitis B surface antigen, Hepatitis B core antibodies, Hepatitis C antibodies, human immunodeficiency virus (HIV)-1, and HIV -2 antibodies.
• •Positive drug screen.
• •History of previous administration of SB010 or any other registered or investigational oligonucleotide-based drug.
• •History or presence of alcohol or drug abuse.
• •Treatment with any known enzyme inducing or inhibiting agents (St. John's Wort, barbiturates, phenothiazines, cimetidine, ketoconazole etc.) within 30 days before administration of IMP or during the trial.
• •Use of any medication (including over-the-counter medication such as herbal products) except allowed concomitant medication within 2 weeks (for biologics: 6 months) before administration of IMP or within \<10 times the elimination half-life of the respective drug, or the duration of the pharmacodynamic effect, whatever is longer, or anticipated concomitant medication during the treatment period.
• •Consumption of any enzyme inducing or inhibiting aliments and beverages (e.g., broccoli, Brussels sprout, star fruit, etc.) within 14 days prior to administration of IMP or during the trial.
• •Consumption of any caffeine- or theophylline-containing product as well as grapefruit and grapefruit-containing products 12 h before administration of IMP.
• •Vegetarian diet or other peculiar dietary habits which would preclude the patient's acceptance of standardised meals.
• •Surgery of the gastrointestinal tract except for appendectomy or herniotomy.
• •Planned donation of germ cells, blood, organs, bone marrow during the course of the trial or within 6 months thereafter.
• •Participation in another clinical trial with an investigational drug or device within the last 3 months. For biologics, the minimum exclusion period is at least 6 months or the time of duration of the pharmacodynamic effect or 10 times the half-life of the respective drug whatever is longer before inclusion in this trial.
• •Blood donation within the last 30 days before screening.
• •Lack of ability or willingness to give informed consent.
• •Anticipated non-availability for trial visits/procedures.
• •Anticipated lack of willingness or inability to cooperate adequately.
• •Vulnerable patients (e.g., persons kept in detention).