The Safety and Pharmacokinetics of Carbavance™ (RPX2014/RPX7009) in Subjects With Renal Insufficiency
Study Details
Study Description
Brief Summary
RPX7009(beta-lactamase inhibitor) is being studied in combination with 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 safety, tolerability and pharmacokinetics of intravenous RPX2014 and RPX7009, administered in combination in subjects with varying degrees of renal insufficiency.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single dose of RPX7009 and RPX2014 Single dose of combination RPX7009 and RPX2014 |
Drug: RPX7009 and RPX2014
The study is designed to enroll approximately 32 subjects. There will be approximately 24 subjects with varying degrees of renal insufficiency and approximately 8 subjects with normal renal function.
|
Outcome Measures
Primary Outcome Measures
- Safety from baseline through the end of the study [7days]
Number of patients with adverse events; assessed by patient reporting, collection of vital signs, ECGs and absolute values and changes over time of hematology, chemistry and urinalysis
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Males and females aged 18 through 80 years of age
-
Willing to abstain from alcohol for 48 hours prior to dosing through discharge
-
Normal volunteer first matched by age (± 10 years), BMI (± 20%), and gender to the mean values of the moderate renal insufficiency group.
-
Have negative test results for HBsAg, anti-HCV antibody and anti-HIV antibody.
-
Voluntarily consent to participate in the study
-
Sexually abstinent or agree to use two approved methods of contraception.
-
Assessment of renal insufficiency for assignment to study groups will be based on measurements of eGFR calculated by the MDRD equation at the Screening Visit to determine eligibility.
Exclusion Criteria:
-
Unstable or new medical conditions (e.g., cardiovascular, respiratory, hepatic, renal, gastrointestinal, autoimmune, endocrine, or neurological disorders)
-
Hypersensitivity or idiosyncratic reaction to β-lactam antibiotics (e.g. penicillins, cephalosporins, or carbapenems)
-
History of clinically significant seizures, head injury, or meningitis.
-
Current evidence or history of malignancy, excluding basal cell carcinoma, in the 2 years prior to Day -1 with no evidence of recurrence.
-
Females who are pregnant, lactating, or have a positive pregnancy test
-
Previously received any dose of Carbavance (RPX2014/RPX7009).
-
Current participation in another investigational study or participation in another investigational clinical study within 30 days prior to the Screening Visit.
-
Blood donation or significant blood loss (i.e., > 500 mL) within 56 days prior to Day
-
Plasma or platelet donation within 14 days prior to Day -1.
-
Any acute illness requiring antibiotic drug therapy within 30 days prior to Day 1 or a febrile illness within 7 days prior to Day 1.
-
Vigorous exercise from 48 hours prior to Day -1 until the day of discharge from the study.
-
Positive urine drug/alcohol test at the Screening Visit or Day -1
-
Concurrent use of medications known to affect the elimination of serum creatinine (e.g., trimethoprim/sulfamethoxazole [Bactrim®] or cimetidine [Tagamet®]) and competitors of renal tubular secretion (e.g., probenecid) within 30 days prior to the first dose of study drug
-
Abnormal and clinically significant findings on physical examination, medical history, serum chemistry, hematology, or urinalysis
-
Use of any other prescription or nonprescription drugs, vitamins, grapefruit/grapefruit juice or dietary or herbal supplements within 14 days prior to Day -1.
-
Oral contraceptives are permitted for birth control.
-
Acetaminophen (≤ 1 g/day) and low-dose ASA (i.e., ≤ 325 mg per day) are permitted.
-
Currently receives hemodialysis or peritoneal dialysis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | DaVita Clinical Research | Lakewood | Colorado | United States | 80228 |
| 2 | DaVita Clinical Research | Minneapolis | Minnesota | United States | 55404 |
Sponsors and Collaborators
- Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Investigators
- Principal Investigator: Chris Galloway, MD, Da Vita Clinical Research
- Principal Investigator: Jolene K Berg, MD, Da Vita Clinical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Rempex 504