A Study to Investigate the Intrapulmonary Lung Penetration of Nacubactam in Healthy Participants

Hoffmann-La Roche21 enrolled

Overview

The purpose of this study is to characterize the intrapulmonary penetration of nacubactam in healthy volunteers. Nacubactam is a novel non-beta-lactam beta-lactamase inhibitor being developed as a combination therapy with the beta-lactam meropenem for the treatment of serious gram-negative bacterial infections. Adult male and female healthy participants will receive a single intravenous infusion of nacubactam co-administered with meropenem and then undergo a bronchoalveolar lavage (BAL) procedure to collect lung epithelial lining fluid (ELF) for measurement of intrapulmonary concentrations of nacubactam and meropenem.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gram-negative Bacterial Infections

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 18 to 60 years of age, inclusive * Healthy, as judged by the Investigator and defined by the absence of evidence of any active or clinically significant chronic disease identified from a detailed medical and surgical history, physical examination including vital signs and 12-lead electrocardiogram (ECG), and laboratory safety test results * Body mass index (BMI) within the range 18-30 kilogram per square meter (kg/m\^2),inclusive * Non-smoker, or former smoker who has abstained from smoking for at least 6 months * Negative pregnancy test and agreement to comply with measures to prevent pregnancy in women * Refrain from sperm donation and agreement to comply with measures to prevent pregnancy in partner of childbearing potential for men Exclusion Criteria: * History of asthma or clinically significant lung disease * Any condition which contraindicates a BAL procedure * History of clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardiovascular, endocrinological, hematological, dermatological, immunological or allergic disease, metabolic disorder, cancer or cirrhosis * Clinically significant change in health status, as judged by the Investigator, or any major illness within the four weeks before screening, or clinically significant acute infection or febrile illness within the 14 days before screening * History of epilepsy (or known seizure disorder), brain lesions or other significant neurological disorders * Participation in any other clinical study involving an investigational medicinal product or device within 3 months before screening * Known history of clinically significant hypersensitivity or urticaria, or severe allergic reaction to any drug, in particular antibiotics * Donation or loss of over 500 milliliter (mL) of blood within the three months before screening

Outcomes

Primary Outcomes

Epithelial Lining Fluid (ELF) Concentration of Nacubactam to Plasma Concentration of Nacubactam Ratio

The ELF to plasma ratio will be calculated from the concentration of nacubactam in ELF and plasma as a measure of the intrapulmonary penetration of nacubactam in healthy participants.

Time frame: At 2, 3, 4, 6 and 8 hours after study drug administration

Secondary Outcomes

ELF Concentration of Meropenem to Plasma Concentration of Meropenem Ratio

The ELF to plasma ratio will be calculated from the concentration of meropenem in ELF and plasma as a measure of the intrapulmonary penetration of meropenem in healthy participants..

Time frame: At 2, 3, 4, 6 and 8 hours after study drug administration

Area Under the Plasma Concentration-Time Curve from time 0 to 8 hours (AUC0-8) of Nacubactam in ELF

Time frame: At 2, 3, 4, 6 and 8 hours after study drug administration

Maximum Concentration (Cmax) of Nacubactam in ELF

Time frame: At 2, 3, 4, 6 and 8 hours after study drug administration

Area Under the Plasma Concentration-Time Curve from Time 0 to 8 Hours (AUC0-8) of Nacubactam in Blood Plasma