Clinical trial NCT03182504: A Study to Investigate the Intrapulmonary Lung Penetration of Nacubactam in Healthy Participants
Official title: A Non-Randomized, Open Label, One Treatment, One Group Study to Investigate the Intrapulmonary Lung Penetration of RO7079901 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gram-negative Bacterial Infections
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-06-09
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Epithelial Lining Fluid (ELF) Concentration of Nacubactam to Plasma Concentration of Nacubactam Ratio
timeFrame: At 2, 3, 4, 6 and 8 hours after study drug administration
Secondary outcomes:
measure: ELF Concentration of Meropenem to Plasma Concentration of Meropenem Ratio
timeFrame: At 2, 3, 4, 6 and 8 hours after study drug administration
measure: Area Under the Plasma Concentration-Time Curve from time 0 to 8 hours (AUC0-8) of Nacubactam in ELF
timeFrame: At 2, 3, 4, 6 and 8 hours after study drug administration
measure: Maximum Concentration (Cmax) of Nacubactam in ELF
timeFrame: At 2, 3, 4, 6 and 8 hours after study drug administration
measure: Area Under the Plasma Concentration-Time Curve from Time 0 to 8 Hours (AUC0-8) of Nacubactam in Blood Plasma
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Maximum Concentration (Cmax) of Nacubactam in Blood Plasma
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Nacubactam
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Clearance (CL) of Nacubactam
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Volume of Distribution of the Central Compartment (Vc) of Nacubactam
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Volume of Distribution at Steady-State (Vss) of Nacubactam
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Area Under the Plasma Concentration-Time Curve from Time 0 to 8 Hours (AUC0-8) of Meropenem in ELF
timeFrame: At 2, 3, 4, 6 and 8 hours after study drug administration
measure: Maximum Concentration (Cmax) of Meropenem in ELF
timeFrame: At 2, 3, 4, 6 and 8 hours after study drug administration
measure: Area Under the Plasma Concentration-Time Curve from Time 0 to 8 hours (AUC0-8) of Meropenem in Blood Plasma
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Maximum Concentration (Cmax) of Meropenem in Blood Plasma
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Time to Reach the Maximum Plasma Concentration (Tmax) of Meropenem
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Clearance (CL) of Meropenem
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Volume of Distribution of the Central Compartment (Vc) of Meropenem
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Volume of Distribution at Steady-State (Vss) of Meropenem
timeFrame: At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
measure: Number of Participants with Adverse Events
timeFrame: From baseline up to 14 days after study drug administration
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pulmonary Associates Clinical Trials (PACT)
state: Arizona
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: