The Safety and Pharmacokinetics of Carbavance™ (RPX2014/RPX7009) in Subjects With Renal Insufficiency

Subjects With Normal Renal Function Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02020434
• Other study ID #: Rempex 504
• Status: Completed
• Phase: Phase 1
• First received: December 10, 2013
• Last updated: March 1, 2018
• Start date: January 2014
• Est. completion date: October 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 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 safety, tolerability and pharmacokinetics of intravenous RPX2014 and RPX7009, administered in combination in subjects with varying degrees of renal insufficiency.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: October 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Renal Insufficiency
• Subjects With Normal Renal Function
• Subjects With Varying Degrees of Renal Insufficiency and

Intervention

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.

Locations

Country	Name	City	State
United States	DaVita Clinical Research	Lakewood	Colorado
United States	DaVita Clinical Research	Minneapolis	Minnesota

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	Safety from baseline through the end of the study	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	7days