Safety, Tolerability, Pharmacokinetics of Intravenous RPX2014 and 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 safety, tolerability and pharmacokinetics of intravenous RPX2014 and RPX7009, administered alone and in combination, in healthy adult subjects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single and multiple dose of RPX7009 Single and multiple dose of RPX7009 |
Drug: RPX7009
Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation in cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.
Other Names:
|
| Experimental: Single and multiple dose of RPX2014 Single and multiple dose of RPX2014 |
Drug: RPX2014
Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation for cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.
|
| Placebo Comparator: Normal Saline Single and multiple dose of normal saline |
Drug: Placebo
Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation for cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.
Other Names:
|
| Experimental: Combination RPX7009 and RPX2014 Single and Multiple dose of Combination RPX7009 and RPX2014 |
Drug: Combination RPX7009 and RPX2014
Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation in cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.
|
Outcome Measures
Primary Outcome Measures
- Safety from baseline through the end of the study [Study Day 1 to Day 14]
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 PK parameters RPX7009, RPX2014, combination of RPX7009 and RPX2014 & placebo following single and multiple dose administration. [Study Day1 to Day 14]
Plasma AUC0-t, AUC0-inf, Cmax, and Tmax.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy adult males and females, 18 to 55 years of age (inclusive) at the time of screening.
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Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
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Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, ECGs, physical examination) as deemed by the PI.
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Non-tobacco/nicotine-containing product users for a minimum of Dose Study 6 months prior to Day 1.
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Voluntarily consent to participate in the study.
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Sexually abstinent or agree to use two approved methods of contraception.
Exclusion Criteria:
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History or presence of significant 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 check-in (Day -1).
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Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
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History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
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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.
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Blood donation or significant blood loss (i.e., > 500 mL) within 56 days prior to Day
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Plasma donation within 7 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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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: Jeffery Loutit, Sponsor GmbH
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Rempex 501