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

NCT03182504 | Completed Phase 1 FDA Drug

• 2 other identifiers: NP397502016-004478-16
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Gram-negative Bacterial Infections

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• ELF Concentration of Meropenem to Plasma Concentration of Meropenem Ratio

  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

Study Arms (1)

Nacubactam Plus Meropenem

EXPERIMENTAL

Participants will receive a single dose of nacubactam co-administered with meropenem.

Drug: nacubactam; Drug: meropenem

Interventions

nacubactam DRUG

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

Also known as: RO7079901

Nacubactam Plus Meropenem

meropenem DRUG

Participants will receive a single 2000 mg IV infusion of meropenem over 1.5 hours.

Also known as: Merrem

Nacubactam Plus Meropenem

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Pulmonary Associates Clinical Trials (PACT)

Phoenix, Arizona, 85006, United States

Location

MeSH Terms

Conditions

Gram-Negative Bacterial Infections

Interventions

nacubactam; Meropenem

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: June 9, 2017
• Study Start: June 15, 2017
• Primary Completion: August 10, 2017
• Study Completion: August 10, 2017
• Last Updated: April 23, 2018

Record last verified: 2018-04

Locations

US (1)