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

Phase 1

Completed

• Conditions: Healthy Volunteers; Bacterial Infections
• Interventions: Drug: RPX2003 (Biapenem); Drug: Placebo

• Registration Number: NCT01702649
• Lead Sponsor: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)

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.

Study Timeline

• Study Start: 2012-08
• Study First Submitted: 2012-09-25
• Study First Submitted QC: 2012-10-04
• Study First Posted: 2012-10-08
• Status Verified: 2012-11
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Last Update Submitted: 2012-11-29
• Last Update Posted: 2012-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RPX2003 (Biapenem)	RPX2003 (Biapenem)	Single and multiple dose of RPX2003 (Biapenem).
Normal Saline	Placebo	Single and multiple doses of normal saline.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (1)

Celerion; 🇺🇸 Tempe, Arizona, United States