Bacterial Infections, Healthy Volunteers
Conditions
Brief summary
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
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.
Interventions
DRUGRPX2003 (Biapenem)
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.
DRUGPlacebo
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.
Sponsors
Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety from baseline through the end of the study. | Study Day 1 to 13. | 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
| Measure | Time frame | Description |
|---|---|---|
| Composite of PK parameters RPX2003 & placebo following single dose administration. | Part 1A Study Day 1 to 3. | plasma AUC0-t, AUC0-inf, Cmax, and Tmax. |
| Composite of PK parameters RPX2003 & placebo following multiple dose administration. | Part 1B Day 4 to 12 | plasma AUC0-t, AUC0-inf, Cmax, and Tmax. |
Countries
United States
Outcome results
None listed