Evaluating the Plasma, Epithelial Lining, and Alveolar Macrophage Concentrations of Intravenous Carbavance™ (RPX2014/RPX7009) in Healthy Adult Subjects
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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)
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetics from baseline through the end of the study [2 days]
Assessment of plasma, ELF and AM concentrations of RPX2014 and RPX7009 after 3 doses of Carbavance
Secondary Outcome Measures
- IV Carbavance concentrations in lung fluid [2 days]
Plasma, ELF and AM concentrations of intravenous Carbavance in healthy adult subjects.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy adult males and/or females, 18 to 55 years of age (inclusive) at the time of screening.
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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.
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Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, electrocardiograms (ECGs), physical examination) as deemed by the PI.
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Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to Day
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Voluntarily consent to participate in the study.
Exclusion Criteria:
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History or presence of significant oncologic, cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
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Positive urine drug/alcohol testing at screening (or Day -1).
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Positive testing for human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg).
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History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
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Hypersensitivity or idiosyncratic reaction to beta-lactam antibiotics (e.g. penicillins, cephalosporins, carbapenems, etc.).
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Clinically significant pulmonary or any other disease that prevents a subject from undergoing bronchoscopy with bronchopulmonary lavage.
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History of seizures (e.g., epilepsy), head injury or meningitis requiring ongoing anti-seizure medications.
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Use of any prescription medication (with the exception of hormonal contraceptives or hormone replacement therapy for females) within 14 days prior to Day 1.
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Participation in another investigational clinical trial within 30 days prior to Day 1.
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Females who are pregnant or lactating.
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Surgery within the past three months prior to Day 1 determined by the PI to be clinically relevant.
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Any acute illness including clinically significant infection within 30 days prior to Day 1.
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QTcF interval >450 msec, or history of prolonged QT syndrome at screening (or Day 1).
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Calculated creatinine clearance less than 80 mL/min (Cockroft-Gault method) at screening.
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Subjects who have any clinically significant abnormalities on laboratory values at screening (or Day -1), including:
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White blood cell count (WBC) < 3,000/mm3, hemoglobin < 11g/dL.
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Absolute neutrophil count < 1,200/mm3 or platelet count < 120,000/mm3.
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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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pulmonary Associates | Phoenix | Arizona | United States | 85006 |
Sponsors and Collaborators
- Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Investigators
- Principal Investigator: Mark Gotfried, MD, Pulmonary Associates
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Rempex 503