We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01897779
First Posted: July 12, 2013
Last Update Posted: April 29, 2014
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 studied in combination with a carbapenem (RPX2014) to treat bacterial infections, including those due to multi-drug resistant bacteria.

Condition Intervention Phase
Healthy Volunteers Bacterial Infections Drug: RPX7009 Drug: RPX2014 Drug: Placebo Drug: Combination RPX7009 and RPX2014 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, 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

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 through the end of the study [ Time Frame: Study Day 1 to Day 14 ]
    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. [ Time Frame: Study Day1 to Day 14 ]
    Plasma AUC0-t, AUC0-inf, Cmax, and Tmax.


Enrollment: 94
Study Start Date: July 2013
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single and multiple dose of RPX7009
Single and multiple dose of RPX7009
Drug: RPX7009
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.
Other Name: (beta-lactamase inhibitor)
Experimental: Single and multiple dose of RPX2014
Single and multiple dose of RPX2014
Drug: RPX2014
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.
Placebo Comparator: Normal Saline
Single and multiple dose of normal saline
Drug: Placebo
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.
Other Name: Normal saline
Experimental: Combination RPX7009 and RPX2014
Single and Multiple dose of Combination RPX7009 and RPX2014
Drug: Combination RPX7009 and RPX2014
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.

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. Healthy adult males and females, 18 to 55 years of age (inclusive) at the time of screening.
  2. Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
  3. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, ECGs, physical examination) as deemed by the PI.
  4. Non-tobacco/nicotine-containing product users for a minimum of Dose Study 6 months prior to Day 1.
  5. Voluntarily consent to participate in the study.
  6. Sexually abstinent or agree to use two approved methods of contraception.

Exclusion Criteria:

  1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
  2. Positive urine drug/alcohol testing at screening or check-in (Day -1).
  3. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
  4. History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
  5. 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.
  6. Blood donation or significant blood loss (i.e., > 500 mL) within 56 days prior to Day 1.
  7. Plasma donation within 7 days prior to Day 1.
  8. Participation in another investigational clinical trial within 30 days prior to Day 1.
  9. 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): NCT01897779


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: Jeffery Loutit Sponsor GmbH
  More Information

Responsible Party: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
ClinicalTrials.gov Identifier: NCT01897779     History of Changes
Other Study ID Numbers: Rempex 501
First Submitted: July 9, 2013
First Posted: July 12, 2013
Last Update Posted: April 29, 2014
Last Verified: April 2014

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