Clinical trial NCT02020434: The Safety and Pharmacokinetics of Carbavance™ (RPX2014/RPX7009) in Subjects With Renal Insufficiency
Official title: A Phase 1, Open-label, Single-dose Study to Determine the Safety and Pharmacokinetics of Carbavance™ (RPX2014/RPX7009) in Subjects With Renal Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Subjects With Varying Degrees of Renal Insufficiency and
Subjects With Normal Renal Function
Lead sponsor: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Sponsor class: INDUSTRY
First posted: 2013-12-25
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Males and females aged 18 through 80 years of age
2. Willing to abstain from alcohol for 48 hours prior to dosing through discharge
3. Normal volunteer first matched by age (± 10 years), BMI (± 20%), and gender to the mean values of the moderate renal insufficiency group.
4. Have negative test results for HBsAg, anti-HCV antibody and anti-HIV antibody.
5. Voluntarily consent to participate in the study
6. Sexually abstinent or agree to use two approved methods of contraception.
7. 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:

1. Unstable or new medical conditions (e.g., cardiovascular, respiratory, hepatic, renal, gastrointestinal, autoimmune, endocrine, or neurological disorders)
2. Hypersensitivity or idiosyncratic reaction to β-lactam antibiotics (e.g. penicillins, cephalosporins, or carbapenems)
3. History of clinically significant seizures, head injury, or meningitis.
4. Current evidence or history of malignancy, excluding basal cell carcinoma, in the 2 years prior to Day -1 with no evidence of recurrence.
5. Females who are pregnant, lactating, or have a positive pregnancy test
6. Previously received any dose of Carbavance (RPX2014/RPX7009).
7. Current participation in another investigational study or participation in another investigational clinical study within 30 days prior to the Screening Visit.
8. Blood donation or significant blood loss (i.e., \> 500 mL) within 56 days prior to Day 1.
9. Plasma or platelet donation within 14 days prior to Day -1.
10. 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.
11. Vigorous exercise from 48 hours prior to Day -1 until the day of discharge from the study.
12. Positive urine drug/alcohol test at the Screening Visit or Day -1
13. 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
14. Abnormal and clinically significant findings on physical examination, medical history, serum chemistry, hematology, or urinalysis
15. Use of any other prescription or nonprescription drugs, vitamins, grapefruit/grapefruit juice or dietary or herbal supplements within 14 days prior to Day -1.

    1. Oral contraceptives are permitted for birth control.
    2. Acetaminophen (≤ 1 g/day) and low-dose ASA (i.e., ≤ 325 mg per day) are permitted.
16. Currently receives hemodialysis or peritoneal dialysis.

Primary outcomes:
measure: Safety from baseline through the end of the study
timeFrame: 7days
Secondary outcomes:
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: DaVita Clinical Research
state: Colorado
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
Study officials:
affiliation: Da Vita Clinical Research
name: Chris Galloway, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Da Vita Clinical Research
name: Jolene K Berg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rubino CM, Bhavnani SM, Loutit JS, Lohse B, Dudley MN, Griffith DC. Single-Dose Pharmacokinetics and Safety of Meropenem-Vaborbactam in Subjects with Chronic Renal Impairment. Antimicrob Agents Chemother. 2018 Feb 23;62(3):e02103-17. doi: 10.1128/AAC.02103-17. Print 2018 Mar.