Intrapulmonary penetration of RO7223280 following intravenous administration Not Applicable
Conditions
Interventions
Participants will receive a single dose of RO7223280, 1000 milligrams (mg), as an IV infusion over a period of 1 hour on Day 1.
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female participants aged 18 to 55 years of age, inclusive, at screening 2. Healthy participants. Health status defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, serology, coagulation, and urinalysis 3. Participants must weigh at least 50 kg and must have a body mass index (BMI) within the range of 18 to 32 kg/m², inclusive
Exclusion criteria
Exclusion criteria: 1. History of any clinically significant gastrointestinal, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, haematological, or allergic disease, metabolic disorder, cancer, or cirrhosis 2. Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study 3. History or evidence of any medical condition potentially altering the absorption, metabolism, or elimination of drugs 4. History or presence of clinically significant ECG abnormalities 5. History of malignancy 6. Vaccination is prohibited within 2 months prior to Day 1 7. Use of glucocorticoids and other immunosuppressive medications is prohibited within 30 days (or within 5 times the elimination half-life, whichever is longer) prior to Day 1 8. Currently enrolled in, have participated in, or plan to participate in any other clinical study involving an investigational medicinal product or medical device study from within 30 days directly preceding screening or within 5 times the elimination half-life, if known (whichever is longer), until completion of the follow-up visit 9. Normal lung function with forced expiratory volume in the first second (FEV1) predicted =80% and FEV1/forced vital capacity (FVC) >0.7. 10. Clinically significant abnormalities in laboratory test results (including complete blood count, chemistry panel, and urinalysis) 11. Evidence of human immunodeficiency virus (HIV) infection and/or positive result for human HIV antibodies 12. Presence of hepatitis B surface antigen or positive hepatitis C antibody test result 13. Participants who may not tolerate a BAL or cannot undergo a BAL because of the presence of contraindications to a BAL including suspected intolerance to medications required for bronchoscopy 14. History of hypersensitivity to lidocaine (and other local anaesthetics of the amino amide type) or to any of its formulation ingredients 15. History of hypersensitivity to any of the excipients in the formulation of RO7223280 16. Participants with insufficient venous access.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Concentrations of RO7223280 in epithelial lining fluid (ELF) (CELF) measured using bronchoalveolar lavage (BAL) and plasma samples collected at a specific timepoint, up to 8 and 12 hours post-dose on Day 1 respectively 2. ELF-to-Plasma ratios of RO7223280 in ELF measured using BAL and plasma samples collected at a specific timepoint, up to 8 hours post-dose on Day 1 3. Concentrations of RO7223280 in alveolar macrophages (AM) measured using BAL and plasma samples collected at a specific timepoint, up to 8 and 12 hours post-dose on Day 1 respectively 4. AM-to-Plasma ratios of RO7223280 in AM measured using BAL and plasma samples collected at a specific timepoint, up to 8 hours post-dose on Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Maximum observed concentration (Cmax) of RO7223280 and its metabolites, as appropriate, in plasma measured using blood samples at pre-dose and at multiple timepoints, up to 12 hours post-dose on Day 1 and thereafter on Days 2, 3 and 4 2. Time to maximum observed concentration (Tmax) of RO7223280 and its metabolites, as appropriate, in plasma measured using blood samples at pre-dose and at multiple timepoints, up to 12 hours post-dose on Day 1 and thereafter on Days 2, 3 and 4 3. Observed plasma concentration at the end of infusion (Cend) of RO7223280 and its metabolites, as appropriate, in plasma measured using blood samples at pre-dose and at multiple timepoints, up to 12 hours post-dose on Day 1 and thereafter on Days 2, 3 and 4 4. Area under the plasma or blood concentration versus time curve from time zero to the last measurable concentration (AUClast) of RO7223280 and its metabolites, as appropriate, in plasma measured using blood samples at pre-dose and at multiple timepoints, up to 12 hours post-dose on Day 1 and thereafter on Days 2, 3 and 4 5. Area under the plasma or blood concentration versus time curve from time zero extrapolated to infinity (AUCinf) of RO7223280 and its metabolites, as appropriate, in plasma measured using blood samples at pre-dose and at multiple timepoints, up to 12 hours post-dose on Day 1 and thereafter on Days 2, 3 and 4 6. Apparent terminal elimination half-life (T1/2), computed as ln(2)/ ?z of RO7223280 and its metabolites, as appropriate, in plasma measured using blood samples at pre-dose and at multiple timepoints, up to 12 hours post-dose on Day 1 and thereafter on Days 2, 3 and 4 7. Terminal rate constant (?z) calculated by linear regression of the log-transformed terminal part of the concentration time curve of RO7223280 and its metabolites, as appropriate, in plasma measured using blood samples at pre-dose and at multiple time | — |
Countries
United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed