Safety, Tolerability, Pharmacokinetics of Intravenous RPX2003 (Biapenem) in Healthy Adult Subjects

Study Overview
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Brief Summary
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RPX2003 (biapenem) is being studied in combination with a beta-lactamase inhibitor to treat bacterial infections, including those due to multi-drug resistant bacteria.

Detailed Description
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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 of biapenem, administered alone, in healthy adult subjects.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Single- and Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics of Intravenous RPX2003 in Healthy Adult Subjects

Conditions
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Healthy Volunteers, Bacterial Infections

Intervention / Treatment
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* Drug: RPX2003 (Biapenem)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 1. 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. Hypersensitivity or idiosyncratic reaction to compounds related to the study drug (e.g. beta-lactam antibiotics such as penicillins, carbapenems, etc). History of seizures (e.g., epilepsy). 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. Blood donation or significant blood loss (i.e., > 500 mL) within 56 days prior to Day 1. Subjects who have any abnormalities on laboratory values at screening or check-in (Day -1).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RPX2003 (Biapenem)<br>Single and multiple dose of RPX2003 (Biapenem). | Drug: RPX2003 (Biapenem)<br>* Six (6) cohorts of 3 active or 8 subjects of 6 active are planned for evaluation. Single dose followed by multiple dose, three times a day.<br>|
| Placebo Comparator: Normal Saline<br>Single and multiple doses of normal saline. | Drug: Placebo<br>* Six (6) cohorts of 1 placebo or 8 subjects of 2 placebo are planned for evaluation. Single dose followed by multiple dose, three times a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Study Day 1 to 13. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of PK parameters RPX2003 & placebo following single dose administration. | plasma AUC0-t, AUC0-inf, Cmax, and Tmax. | Part 1A Study Day 1 to 3. | 
| Composite of PK parameters RPX2003 & placebo following multiple dose administration. | plasma AUC0-t, AUC0-inf, Cmax, and Tmax. | Part 1B Day 4 to 12 |