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.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections; Healthy Volunteers
• Intervention / Treatment: Drug: RPX2003 (Biapenem); Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RPX2003 (Biapenem); Single and multiple dose of RPX2003 (Biapenem).	Drug: RPX2003 (Biapenem); Six (6) cohorts of 3 active or 8 subjects of 6 active are planned for evaluation. Single dose followed by multiple dose, three times a day.
Placebo Comparator: Normal Saline; Single and multiple doses of normal saline.	Drug: Placebo; Six (6) cohorts of 1 placebo or 8 subjects of 2 placebo are planned for evaluation. Single dose followed by multiple dose, three times a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety from baseline through the end of the study.	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.	Study Day 1 to 13.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of PK parameters RPX2003 & placebo following single dose administration.	plasma AUC0-t, AUC0-inf, Cmax, and Tmax.	Part 1A Study Day 1 to 3.
Composite of PK parameters RPX2003 & placebo following multiple dose administration.	plasma AUC0-t, AUC0-inf, Cmax, and Tmax.	Part 1B Day 4 to 12

Collaborators and Investigators

• Sponsor: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
• Investigators: Study Director: Jeff Loutit, MBChB, Sponsor GmbH

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: September 25, 2012
• First Submitted That Met QC Criteria: October 4, 2012
• First Posted (Estimate): October 8, 2012

Study Record Updates

• Last Update Posted (Estimate): December 3, 2012
• Last Update Submitted That Met QC Criteria: November 29, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Anti-Infective Agents; Biapenem
• Other Study ID Numbers: Rempex 401