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

A Non-Randomized, Open Label, One Treatment, One Group Study to Investigate the Intrapulmonary Lung Penetration of RO7079901 in Healthy Volunteers

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 Overview

• Status: Completed
• Conditions: Gram-negative Bacterial Infections
• Intervention / Treatment: Drug: nacubactam; Drug: meropenem

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates Clinical Trials (PACT)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nacubactam Plus Meropenem; Participants will receive a single dose of nacubactam co-administered with meropenem.	Drug: nacubactam; Participants will receive a single 2000 milligram (mg) intravenous (IV) infusion of nacubactam over 1.5 hours.; Other Names: RO7079901; Drug: meropenem; Participants will receive a single 2000 mg IV infusion of meropenem over 1.5 hours.; Other Names: Merrem

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At 2, 3, 4, 6 and 8 hours after study drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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..	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		At 2, 3, 4, 6 and 8 hours after study drug administration
Maximum Concentration (Cmax) of Nacubactam in ELF		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		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Maximum Concentration (Cmax) of Nacubactam in Blood Plasma		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Time to Reach the Maximum Plasma Concentration (Tmax) of Nacubactam		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Clearance (CL) of Nacubactam		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Volume of Distribution of the Central Compartment (Vc) of Nacubactam		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Volume of Distribution at Steady-State (Vss) of Nacubactam		At 0, 0.75, 1.5, 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 Meropenem in ELF		At 2, 3, 4, 6 and 8 hours after study drug administration
Maximum Concentration (Cmax) of Meropenem in ELF		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 Meropenem in Blood Plasma		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Maximum Concentration (Cmax) of Meropenem in Blood Plasma		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Time to Reach the Maximum Plasma Concentration (Tmax) of Meropenem		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Clearance (CL) of Meropenem		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Volume of Distribution of the Central Compartment (Vc) of Meropenem		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Volume of Distribution at Steady-State (Vss) of Meropenem		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Number of Participants with Adverse Events	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	From baseline up to 14 days after study drug administration

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2017
• Primary Completion (Actual): August 10, 2017
• Study Completion (Actual): August 10, 2017

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 7, 2017
• First Posted (Actual): June 9, 2017

Study Record Updates

• Last Update Posted (Actual): April 23, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Gram-Negative Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Meropenem
• Other Study ID Numbers: NP39750; 2016-004478-16 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No