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

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.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections; Healthy Volunteers
• Intervention / Treatment: Drug: RPX7009; 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 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.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

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: Ascending Single and Multiple dose of RPX7009	Drug: RPX7009; Ten (10) cohorts of 8 subjects (6 active and 2 placebo) are planned for evaluation.; Other Names: (beta-lactamase inhibitor)
Placebo Comparator: Normal Saline; Ascending Single and multiple dose of normal saline.	Drug: Placebo; Ten (10) cohorts of 8 subjects (6 active and 2 placebo) are planned for evaluation.; Other Names: Normal saline

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 Day 13.

Secondary Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Griffith DC, Loutit JS, Morgan EE, Durso S, Dudley MN. Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of the beta-Lactamase Inhibitor Vaborbactam (RPX7009) in Healthy Adult Subjects. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6326-32. doi: 10.1128/AAC.00568-16. Print 2016 Oct.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: December 13, 2012
• First Submitted That Met QC Criteria: December 14, 2012
• First Posted (Estimate): December 17, 2012

Study Record Updates

• Last Update Posted (Estimate): July 24, 2013
• Last Update Submitted That Met QC Criteria: July 22, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors
• Other Study ID Numbers: Rempex 402