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Safety, Tolerability, Pharmacokinetics of Intravenous RPX2014 and RPX7009 in Healthy Adult Subjects

Primary Purpose

Healthy Volunteers, Bacterial Infections

Status

Completed

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

RPX7009

RPX2014

Placebo

Combination RPX7009 and RPX2014

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 females, 18 to 55 years of age (inclusive) at the time of screening.
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 (e.g., laboratory profiles, medical histories, ECGs, physical examination) as deemed by the PI.
Non-tobacco/nicotine-containing product users for a minimum of Dose Study 6 months prior to Day 1.
Voluntarily consent to participate in the study.
Sexually abstinent or agree to use two approved methods of contraception.

Exclusion Criteria:

History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
Positive urine drug/alcohol testing at screening or check-in (Day -1).
Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
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.
Plasma donation within 7 days prior to Day 1.
Participation in another investigational clinical trial within 30 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

Experimental

Placebo Comparator

Experimental

Arm Label

Single and multiple dose of RPX7009

Single and multiple dose of RPX2014

Normal Saline

Combination RPX7009 and RPX2014

Arm Description

Single and multiple dose of RPX7009

Single and multiple dose of RPX2014

Single and multiple dose of normal saline

Single and Multiple dose of Combination RPX7009 and RPX2014

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Composite of PK parameters RPX7009, RPX2014, combination of RPX7009 and RPX2014 & placebo following single and multiple dose administration.

Plasma AUC0-t, AUC0-inf, Cmax, and Tmax.

Full Information

NCT ID

NCT01897779

First Posted

July 9, 2013

Last Updated

April 27, 2014

Sponsor

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

1. Study Identification

Unique Protocol Identification Number

NCT01897779

Brief Title

Safety, Tolerability, Pharmacokinetics of Intravenous RPX2014 and RPX7009 in Healthy Adult Subjects

Official Title

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple Ascending-dose Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous RPX2014 and RPX7009 Alone and in Combination in Healthy Adult Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

April 2014

Overall Recruitment Status

Completed

Study Start Date

July 2013 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

February 2014 (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 studied in combination with a carbapenem (RPX2014) 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 (RPX2014) 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 intravenous RPX2014 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

94 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single and multiple dose of RPX7009

Arm Type

Experimental

Arm Description

Single and multiple dose of RPX7009

Arm Title

Single and multiple dose of RPX2014

Arm Type

Experimental

Arm Description

Single and multiple dose of RPX2014

Arm Title

Normal Saline

Arm Type

Placebo Comparator

Arm Description

Single and multiple dose of normal saline

Arm Title

Combination RPX7009 and RPX2014

Arm Type

Experimental

Arm Description

Single and Multiple dose of Combination RPX7009 and RPX2014

Intervention Type

Drug

Intervention Name(s)

RPX7009

Other Intervention Name(s)

(beta-lactamase inhibitor)

Intervention Description

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation in cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Intervention Type

Drug

Intervention Name(s)

RPX2014

Intervention Description

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation for cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Normal saline

Intervention Description

Intervention Type

Drug

Intervention Name(s)

Combination RPX7009 and RPX2014

Intervention Description

Primary Outcome Measure Information:

Title

Safety from baseline through 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

Study Day 1 to Day 14

Secondary Outcome Measure Information:

Title

Composite of PK parameters RPX7009, RPX2014, combination of RPX7009 and RPX2014 & placebo following single and multiple dose administration.

Description

Plasma AUC0-t, AUC0-inf, Cmax, and Tmax.

Time Frame

Study Day1 to Day 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 females, 18 to 55 years of age (inclusive) at the time of screening. 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 (e.g., laboratory profiles, medical histories, ECGs, physical examination) as deemed by the PI. Non-tobacco/nicotine-containing product users for a minimum of Dose Study 6 months prior to Day 1. Voluntarily consent to participate in the study. Sexually abstinent or agree to use two approved methods of contraception. Exclusion Criteria: History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease. Positive urine drug/alcohol testing at screening or check-in (Day -1). Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV). History or presence of alcoholism or drug abuse within the 2 years prior to Day 1. 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. Plasma donation within 7 days prior to Day 1. Participation in another investigational clinical trial within 30 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

Jeffery Loutit

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

Citations:

PubMed Identifier

29437614

Citation

Rubino CM, Bhavnani SM, Loutit JS, Morgan EE, White D, Dudley MN, Griffith DC. Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Vaborbactam and Meropenem Alone and in Combination following Single and Multiple Doses in Healthy Adult Subjects. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e02228-17. doi: 10.1128/AAC.02228-17. Print 2018 Apr.

Results Reference

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Safety, Tolerability, Pharmacokinetics of Intravenous RPX2014 and RPX7009 in Healthy Adult Subjects

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