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

Gram-negative Bacterial Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03182504
• Other study ID #: NP39750
• Secondary ID: 2016-004478-16
• Status: Completed
• Phase: Phase 1
• First received: June 7, 2017
• Last updated: April 20, 2018
• Start date: June 15, 2017
• Est. completion date: August 10, 2017

Study information

• Verified date: April 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 10, 2017
• Est. primary completion date: August 10, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Bacterial Infections
• Gram-Negative Bacterial Infections

Intervention

Drug:
• nacubactam
Participants will receive a single 2000 milligram (mg) intravenous (IV) infusion of nacubactam over 1.5 hours.
• meropenem
Participants will receive a single 2000 mg IV infusion of meropenem over 1.5 hours.

Locations

Country	Name	City	State
United States	Pulmonary Associates Clinical Trials (PACT)	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Maximum Concentration (Cmax) of Nacubactam in ELF		At 2, 3, 4, 6 and 8 hours after study drug administration
Secondary	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
Secondary	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
Secondary	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
Secondary	Clearance (CL) of Nacubactam		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Secondary	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
Secondary	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
Secondary	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
Secondary	Maximum Concentration (Cmax) of Meropenem in ELF		At 2, 3, 4, 6 and 8 hours after study drug administration
Secondary	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
Secondary	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
Secondary	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
Secondary	Clearance (CL) of Meropenem		At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration
Secondary	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
Secondary	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
Secondary	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