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

Phase 1

Completed

Interventions: Drug: RPX2014
Drug: Placebo
Drug: Combination RPX7009 and RPX2014
Drug: RPX7009

Lead Sponsor: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)

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.

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.

Recruitment & Eligibility

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).

Arm && Interventions

Group	Intervention	Description
Single and multiple dose of RPX2014	RPX2014	Single and multiple dose of RPX2014
Normal Saline	Placebo	Single and multiple dose of normal saline
Combination RPX7009 and RPX2014	Combination RPX7009 and RPX2014	Single and Multiple dose of Combination RPX7009 and RPX2014
Single and multiple dose of RPX7009	RPX7009	Single and multiple dose of RPX7009

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.