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

Healthy Subjects Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02073812
• Other study ID #: Rempex 503
• Status: Completed
• Phase: Phase 1
• First received: February 14, 2014
• Last updated: March 1, 2018
• Start date: February 2014
• Est. completion date: April 2014

Study information

• Verified date: March 2018
• Source: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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).

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

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)

Locations

Country	Name	City	State
United States	Pulmonary Associates	Phoenix	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	IV Carbavance concentrations in lung fluid	Plasma, ELF and AM concentrations of intravenous Carbavance in healthy adult subjects.	2 days