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

Phase 1

Completed

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

Brief Summary: RPX7009 (beta-lactamase inhibitor) is being studies in combination with a carbapenem biapenem 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 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 RPX7009, administered alone, in healthy adult subjects.

Recruitment & Eligibility

Inclusion Criteria

Healthy adult males and/or females (of Non Child-bearing potential), 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.
Documented hypersensitivity reaction or anaphylaxis to any medication.
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.
Plasma donation within 7 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
Ascending Single and Multiple dose of RPX7009	RPX7009	Ascending Single and Multiple dose of RPX7009
Normal Saline	Placebo	Ascending Single and multiple dose of normal saline.

Primary Outcome Measures

Name	Time	Method
Safety from baseline through the end of the study.	Study Day 1 to Day 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 Outcome Measures

Name	Time	Method
Composite of PK parameters RPX7009 & placebo following single dose administration.	Study Day 1 to Day 12	Plasma AUC0-t, AUC0-inf, Cmax, and Tmax.