Safety Study of Intravenous Biapenem (RPX2003) and RPX7009 Given Alone and in Combination
Study Details
Study Description
Brief Summary
RPX7009 (beta-lactamase inhibitor) is being studies in combination with a carbapenem biapenem 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 (RPX2003 or biapenem) 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 and pharmacodynamics of Intravenous Biapenem and RPX7009, administered alone and in combination in healthy adult subjects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Normal saline Single and multiple dose of normal saline |
Drug: Normal saline
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Names:
|
| Experimental: Single dose IV of biapenem or RPX7009 Single dose IV infusion of biapenem or RPX7009 |
Drug: RPX7009
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Names:
Drug: Biapenem
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Names:
|
| Experimental: Single dose of biapenem or RPX7009 Single IV dose of biapenem or RPX7009 (for those on active drug, this will be the drug not given in the first IV treatment) |
Drug: RPX7009
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Names:
Drug: Biapenem
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Names:
|
| Experimental: Biapenem and RPX7009 in combination Single dose followed by a multiple dose of biapenem and RPX7009 in combination |
Drug: RPX7009
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Names:
Drug: Biapenem
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Safety from baseline to the end of the study [Day 1 - Day 17]
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.
Secondary Outcome Measures
- Composite of Pharmacokinetic (PK) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration. [Day 1 - Day 14]
Comparison will be performed between the cohorts for the plasma AUC0-t, AUC0-inf, Cmax, and Tmax. Urine PK parameters such as amount excreted and % dose excreted will be calculated from urinary excretion data.
- Composite of Pharmacodynamic (PD) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration. [Days 1-14]
Serum for bactericidal titers (SBT) assessments will be collected on Days 1, 4, 7 and 14 (at the end-of-infusion (EOI)), and at 2, 4, and 8 hours after start of infusion.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy adult males and/or females, 18 to 55 years of age
-
Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
-
Medically healthy with clinically insignificant screening results
-
Non-tobacco/nicotine-containing product users for a minimum of 6 months prior to Day
- Sexually abstinent or use acceptable methods of birth control
Exclusion Criteria:
-
History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
-
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.).
-
Use of any over-the-counter (OTC) medication, including herbal products and vitamins, within the 7 days prior to Day 1. Up to 2 grams per day of acetaminophen is allowed for acute events at the discretion of the PI.
-
Plasma donation within 7 days prior to Day 1.
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Subjects who have any abnormalities on laboratory values at screening or check-in (Day -1).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CMAX | Adelaide | South Australia | Australia | 5000 |
Sponsors and Collaborators
- Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Investigators
- Study Director: Jefferey Loutit, MBChB, Sponsor GmbH
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Rempex 403