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Safety Study of Intravenous Biapenem (RPX2003) and RPX7009 Given Alone and in Combination

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01772836
First Posted: January 21, 2013
Last Update Posted: July 11, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
  Purpose
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.

Condition Intervention Phase
Healthy Volunteers Bacterial Infections Drug: RPX7009 Drug: Biapenem Drug: Normal saline Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Single and Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous Biapenem (RPX2003) and RPX7009 Given Alone and in Combination in Healthy Adult Subjects.

Resource links provided by NLM:


Further study details as provided by Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company):

Primary Outcome Measures:
  • Safety from baseline to the end of the study [ Time Frame: Day 1 - Day 17 ]
    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:
  • Composite of Pharmacokinetic (PK) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration. [ Time Frame: Day 1 - Day 14 ]

    Comparison will be performed between the cohorts for the plasma AUC0-t, AUC0-inf, Cmax, and Tmax.

    Urine PK parameters such as amount excreted and % dose excreted will be calculated from urinary excretion data.


  • Composite of Pharmacodynamic (PD) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration. [ Time Frame: Days 1-14 ]
    Serum for bactericidal titers (SBT) assessments will be collected on Days 1, 4, 7 and 14 (at the end-of-infusion (EOI)), and at 2, 4, and 8 hours after start of infusion.


Estimated Enrollment: 30
Study Start Date: March 2013
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Normal saline
Single and multiple dose of normal saline
Drug: Normal saline
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Name: Placebo
Experimental: Single dose IV of biapenem or RPX7009
Single dose IV infusion of biapenem or RPX7009
Drug: RPX7009
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Name: (beta-lactamase inhibitor)
Drug: Biapenem
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Name: RPX2003
Experimental: Single dose of biapenem or RPX7009
Single IV dose of biapenem or RPX7009 (for those on active drug, this will be the drug not given in the first IV treatment)
Drug: RPX7009
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Name: (beta-lactamase inhibitor)
Drug: Biapenem
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Name: RPX2003
Experimental: Biapenem and RPX7009 in combination
Single dose followed by a multiple dose of biapenem and RPX7009 in combination
Drug: RPX7009
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Name: (beta-lactamase inhibitor)
Drug: Biapenem
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
Other Name: RPX2003

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 and pharmacodynamics of Intravenous Biapenem and RPX7009, administered alone and in combination in healthy adult subjects.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 beta-lactam antibiotics (e.g. penicillins, cephalosporins, carbapenems, etc.).
  • 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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01772836


Locations
Australia, South Australia
CMAX
Adelaide, South Australia, Australia, 5000
Sponsors and Collaborators
Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Investigators
Study Director: Jefferey Loutit, MBChB Sponsor GmbH
  More Information

Responsible Party: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
ClinicalTrials.gov Identifier: NCT01772836     History of Changes
Other Study ID Numbers: Rempex 403
First Submitted: January 16, 2013
First Posted: January 21, 2013
Last Update Posted: July 11, 2013
Last Verified: July 2013

Additional relevant MeSH terms:
Bacterial Infections
Biapenem
Thienamycins
beta-Lactamase Inhibitors
Anti-Infective Agents
Anti-Bacterial Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action