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

This study is currently recruiting participants.

Verified March 2013 by Rempex Pharmaceuticals

Sponsor:

Information provided by (Responsible Party):

Rempex Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01772836

First received: January 16, 2013

Last updated: March 18, 2013

Last verified: March 2013

History of Changes

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 Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, 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:

MedlinePlus related topics: Bacterial Infections

U.S. FDA Resources

Further study details as provided by Rempex Pharmaceuticals:

Primary Outcome Measures:

Safety from baseline to the end of the study [ Time Frame: Day 1 - Day 17 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	May 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

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01772836

Contacts

Contact: Elizabeth Morgan	858-875-6671	lmorgan@rempexpharma.com
Contact: Jefferey Loutit, MBChB	858-875-6665	jloutit@rempexpharma.com

Locations

Australia, South Australia
CMAX	Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Sepehr Shakib, MB, BS, (Hons) PhD FRACP
Principal Investigator: Sepehr Shakib, MB, BS, (Hons) PhD FRACP

Sponsors and Collaborators

Rempex Pharmaceuticals

Investigators

Study Director:

Jefferey Loutit, MBChB

Sponsor GmbH

More Information

No publications provided

Responsible Party:	Rempex Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT01772836 History of Changes
Other Study ID Numbers:	Rempex 403
Study First Received:	January 16, 2013
Last Updated:	March 18, 2013
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration United States: Food and Drug Administration

Additional relevant MeSH terms:

Bacterial Infections
Biapenem
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013

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