Phase-I trial with healthy subjects
Conditions
Interventions
Group 1: E64d Solution for Inhalation, 0.4 ml in ascending doses, single-dose:
Dose-level 1: 0.0136 mg,
Dose-level 2: 0.136 mg,
Dose-level 3: 0.340 mg,
Dose-level 4: 0.850 mg,
Dose-level 5: 2.176 mg,
Sponsors
Universitätsklinikum Freiburg vertreten durch den Leitenden Ärztlichen Direktor und die Kaufmännische Direktorin
Eligibility
Sex/Gender
Male
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent Form (ICF), including consent to use effective contraceptive methods (sexual abstinence or condoms) during the trial and for three months after the end of the study 2. Male subjects 3. Electrocardiogram (ECG) without clinically significant abnormalities (including QTc < 450 ms) 4. Age = 18 and < 65 years at the time of signing ICF 5. Body mass index (BMI) = 18 and = 30 6. Normally active and in good health by medical history and physical examination 7. FEV1 (one-second capacity) must be greater than or equal to the Lower Limit of Normal, which corresponds to the 5% percentile (zscore of -1.645)
Exclusion criteria
Exclusion criteria: 1. Enrollment in any interventional clinical trial in the previous 6 months 2. Healthy volunteers being unable to follow study instructions and not understanding basics and risks of the study 3. Underlying condition that may interfere with inhalation of the IMP 4. Current acute or chronic condition (including airway infection (cough, purulent sputum), fever, chronic obstructive pulmonary disease (COPD), asthma, or other severe respiratory disease, cardiovascular disease, diabetes mellitus, obesity, malignant and autoimmune diseases) unless considered clinically irrelevant and stable by the investigator 5. History of allergies 6. Renal insufficiency (estimated glomerular filtration rate [eGFR] 400 mL) within 90 days before the dosing of Investigational medicinal product (IMP) 12. Consumed alcohol in the 4 days prior to dosing 13. Anamnestic any therapies within 90 days prior to dosing. Nonprescriptive drugs within 90 days prior to dosing are allowed by investigators judgement. 14. Failure to provide contact details of a person with unimpeded access to the trial participant for 24h after inhalation of IMP, who can call for help in case of emergency situations caused by adverse reactions occurring after discharge from the clinic.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of single dosing of inhaled E64d in comparison to placebo: - Number and severity of adverse events (AE), serious AEs (SAEs), treatment emergent AEs (TEAEs), AEs of special interest (AESI) after start of treatment for all dose-levels of E64d solution for inhalation and placebo until day 4. - Change from baseline and frequency of out of range values for all safety variables measured for all dose-levels from signing of ICF until End of Study (EOS). | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): The following PK parameters will be determined for the active drug molecules (E64d and E64c (loxistatin)) in plasma at all applied dose levels: Cmax, tmax, AUC0-t, AUC0-inf, Cl/f*, Vz/f*, terminal elimination rate (lambda_z), terminal elimination half-life (t1/2). E64d and E64c concentration in plasma will be determined 0 -2 h predose, and 3, 10, 20, 30, 40, 50 minutes, 1, 1.5, 2, 4, 6 and 8 h after start of single dose inhalation of E64d solution. | — |
Countries
Germany
Contacts
Public ContactSebastian Fähndrich
Universitätsklinikum Freiburg, Department Innere Medizin, Klinik für Pneumologie
Outcome results
None listed