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

Primary Purpose

Healthy Volunteers, Bacterial Infections

Status

Completed

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

RPX7009

Biapenem

Normal saline

About this trial

This is an interventional treatment trial for Healthy Volunteers

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

CMAX

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Arm Label

Normal saline

Single dose IV of biapenem or RPX7009

Single dose of biapenem or RPX7009

Biapenem and RPX7009 in combination

Arm Description

Single and multiple dose of normal saline

Single dose IV infusion 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)

Single dose followed by a multiple dose of biapenem and RPX7009 in combination

Outcomes

Primary Outcome Measures

Safety from baseline to 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.

Secondary Outcome Measures

Composite of Pharmacokinetic (PK) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration.

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.

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.

Full Information

NCT ID

NCT01772836

First Posted

January 16, 2013

Last Updated

July 9, 2013

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT01772836

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

July 2013

Overall Recruitment Status

Completed

Study Start Date

March 2013 (undefined)

Primary Completion Date

March 2013 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

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

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Healthy Volunteers, Bacterial Infections

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Normal saline

Arm Type

Placebo Comparator

Arm Description

Single and multiple dose of normal saline

Arm Title

Single dose IV of biapenem or RPX7009

Arm Type

Experimental

Arm Description

Single dose IV infusion of biapenem or RPX7009

Arm Title

Single dose of biapenem or RPX7009

Arm Type

Experimental

Arm Description

Single IV dose of biapenem or RPX7009 (for those on active drug, this will be the drug not given in the first IV treatment)

Arm Title

Biapenem and RPX7009 in combination

Arm Type

Experimental

Arm Description

Single dose followed by a multiple dose of biapenem and RPX7009 in combination

Intervention Type

Drug

Intervention Name(s)

RPX7009

Other Intervention Name(s)

(beta-lactamase inhibitor)

Intervention Description

Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)

Intervention Type

Drug

Intervention Name(s)

Biapenem

Other Intervention Name(s)

RPX2003

Intervention Description

Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)

Intervention Type

Drug

Intervention Name(s)

Normal saline

Other Intervention Name(s)

Placebo

Intervention Description

Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)

Primary Outcome Measure Information:

Title

Safety from baseline to the end of the study

Description

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.

Time Frame

Day 1 - Day 17

Secondary Outcome Measure Information:

Title

Composite of Pharmacokinetic (PK) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration.

Description

Time Frame

Day 1 - Day 14

Title

Composite of Pharmacodynamic (PD) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration.

Description

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.

Time Frame

Days 1-14

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jefferey Loutit, MBChB

Organizational Affiliation

Sponsor GmbH

Official's Role

Study Director

Facility Information:

Facility Name

CMAX

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

12. IPD Sharing Statement

Learn more about this trial

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

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