Evaluating the Plasma, Epithelial Lining, and Alveolar Macrophage Concentrations of Intravenous Carbavance™ (RPX2014/RPX7009) in Healthy Adult Subjects

A Phase 1, Randomized, Open-Label, Trial Evaluating the Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Intravenous Carbavance™ (RPX2014/RPX7009) in Healthy Adult Subjects

RPX7009(beta-lactamase inhibitor) is being studied in combination with a carbapenem (RPX2014) to treat bacterial infections, including those due to multi-drug resistant bacteria.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: RPX7009 and RPX2014

Detailed Description

The worldwide spread of resistance to antibiotics among Gram-negative bacteria, particularly members of the ESKAPE group of pathogens, has resulted in a crisis in the treatment of hospital acquired infections. In particular, the recent dissemination of a serine carbapenemase (e.g., KPC) in Enterobacteriaceae in US hospitals now poses a considerable threat to the carbapenems and other members of the beta-lactam class of antimicrobial agents.

Rempex is developing a fixed combination antibiotic of a carbapenem (RPX2014) plus a new beta-lactamase inhibitor (RPX7009) which has activity against serine beta-lactamases, including KPC. This Phase 1 study will assess the pharmacokinetics of intravenous RPX2014 and RPX7009 in plasma and epithelial fluid.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Pulmonary Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy adult males and/or females, 18 to 55 years of age (inclusive) at the time of screening.
2. Body mass index (BMI) ≥ 18.5 and ≤ 30 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive) at the time of screening.
3. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, electrocardiograms (ECGs), physical examination) as deemed by the PI.
4. Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to Day 1.
5. Voluntarily consent to participate in the study.

Exclusion Criteria:

1. History or presence of significant oncologic, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
2. Positive urine drug/alcohol testing at screening (or Day -1).
3. Positive testing for human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg).
4. History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
5. Hypersensitivity or idiosyncratic reaction to beta-lactam antibiotics (e.g. penicillins, cephalosporins, carbapenems, etc.).
6. Clinically significant pulmonary or any other disease that prevents a subject from undergoing bronchoscopy with bronchopulmonary lavage.
7. History of seizures (e.g., epilepsy), head injury or meningitis requiring ongoing anti-seizure medications.
8. Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to Day 1.
9. Participation in another investigational clinical trial within 30 days prior to Day 1.
10. Females who are pregnant or lactating.
11. Surgery within the past three months prior to Day 1 determined by the PI to be clinically relevant.
12. Any acute illness including clinically significant infection within 30 days prior to Day 1.
13. QTcF interval >450 msec, or history of prolonged QT syndrome at screening (or Day 1).
14. Calculated creatinine clearance less than 80 mL/min (Cockroft-Gault method) at screening.

15. Subjects who have any clinically significant abnormalities on laboratory values at screening (or Day -1), including:

    1. White blood cell count (WBC) < 3,000/mm3, hemoglobin < 11g/dL.
    2. Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm3.
16. Liver function abnormalities at screening (or Day -1) (defined by an elevation in bilirubin, AST or ALT 1.5 x ULN of the normal range for subjects based on age and sex).

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: Multiple dose of Carbavance (RPX7009/RPX2014); Multiple dose of Carbavance	Drug: RPX7009 and RPX2014; The study is designed to enroll approximately 25 healthy subjects. The study will evaluate the plasma, epithelial lining fluid, and alveolar macrophage concentrations of Carbavance (RPX7009/RPX2014)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics from baseline through the end of the study	Assessment of plasma, ELF and AM concentrations of RPX2014 and RPX7009 after 3 doses of Carbavance	2 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IV Carbavance concentrations in lung fluid	Plasma, ELF and AM concentrations of intravenous Carbavance in healthy adult subjects.	2 days

Collaborators and Investigators

• Sponsor: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
• Investigators: Principal Investigator: Mark Gotfried, MD, Pulmonary Associates

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: February 14, 2014
• First Submitted That Met QC Criteria: February 25, 2014
• First Posted (Estimate): February 27, 2014

Study Record Updates

• Last Update Posted (Actual): March 5, 2018
• Last Update Submitted That Met QC Criteria: March 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: Rempex 503