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

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

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

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.

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).