Safety, Tolerability, Pharmacokinetics of Intravenous RPX2014 and RPX7009 in Healthy Adult Subjects

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.

Inclusion criteria

• Healthy adult males and females, 18 to 55 years of age (inclusive) at the time of screening.
• 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 (e.g., laboratory profiles, medical histories, ECGs, physical examination) as deemed by the PI.
• Non-tobacco/nicotine-containing product users for a minimum of Dose Study 6 months prior to Day 1.
• Voluntarily consent to participate in the study.
• Sexually abstinent or agree to use two approved methods of contraception.

Exclusion criteria

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
• Positive urine drug/alcohol testing at screening or check-in (Day -1).
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
• History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
• 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.
• Plasma donation within 7 days prior to Day 1.
• Participation in another investigational clinical trial within 30 days prior to Day 1.
• Subjects who have any abnormalities on laboratory values at screening or check-in (Day -1).