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

Primary Purpose

Gram-negative Bacterial Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

nacubactam

meropenem

About this trial

This is an interventional treatment trial for Gram-negative Bacterial Infections

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Pulmonary Associates Clinical Trials (PACT)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nacubactam Plus Meropenem

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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..

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

Maximum Concentration (Cmax) of Nacubactam in ELF

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

Maximum Concentration (Cmax) of Nacubactam in Blood Plasma

Time to Reach the Maximum Plasma Concentration (Tmax) of Nacubactam

Clearance (CL) of Nacubactam

Volume of Distribution of the Central Compartment (Vc) of Nacubactam

Volume of Distribution at Steady-State (Vss) of Nacubactam

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

Maximum Concentration (Cmax) of Meropenem in ELF

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

Maximum Concentration (Cmax) of Meropenem in Blood Plasma

Time to Reach the Maximum Plasma Concentration (Tmax) of Meropenem

Clearance (CL) of Meropenem

Volume of Distribution of the Central Compartment (Vc) of Meropenem

Volume of Distribution at Steady-State (Vss) of Meropenem

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.

Full Information

NCT ID

NCT03182504

First Posted

June 7, 2017

Last Updated

April 20, 2018

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT03182504

Brief Title

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

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Completed

Study Start Date

June 15, 2017 (Actual)

Primary Completion Date

August 10, 2017 (Actual)

Study Completion Date

August 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gram-negative Bacterial Infections

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Nacubactam Plus Meropenem

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

nacubactam

Other Intervention Name(s)

RO7079901

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

meropenem

Other Intervention Name(s)

Merrem

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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 Outcome Measure Information:

Title

ELF Concentration of Meropenem to Plasma Concentration of Meropenem Ratio

Description

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

Title

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

Title

Maximum Concentration (Cmax) of Nacubactam in ELF

Time Frame

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

Title

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

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Maximum Concentration (Cmax) of Nacubactam in Blood Plasma

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Time to Reach the Maximum Plasma Concentration (Tmax) of Nacubactam

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Clearance (CL) of Nacubactam

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Volume of Distribution of the Central Compartment (Vc) of Nacubactam

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Volume of Distribution at Steady-State (Vss) of Nacubactam

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

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

Time Frame

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

Title

Maximum Concentration (Cmax) of Meropenem in ELF

Time Frame

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

Title

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

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Maximum Concentration (Cmax) of Meropenem in Blood Plasma

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Time to Reach the Maximum Plasma Concentration (Tmax) of Meropenem

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Clearance (CL) of Meropenem

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Volume of Distribution of the Central Compartment (Vc) of Meropenem

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Volume of Distribution at Steady-State (Vss) of Meropenem

Time Frame

At 0, 0.75, 1.5, 2, 3, 4, 6 and 8 hours after study drug administration

Title

Number of Participants with Adverse Events

Description

Time Frame

From baseline up to 14 days after study drug administration

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Pulmonary Associates Clinical Trials (PACT)

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85006

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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