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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
ClinicalTrials.gov Identifier:
NCT01897779
First received: July 9, 2013
Last updated: April 27, 2014
Last verified: April 2014
  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
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, 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 ] [ 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 PK parameters RPX7009, RPX2014, combination of RPX7009 and RPX2014 & placebo following single and multiple dose administration. [ Time Frame: Study Day1 to Day 14 ] [ Designated as safety issue: No ]
    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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

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

No publications provided

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
Study First Received: July 9, 2013
Last Updated: April 27, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
United States: Food and Drug Administration

Additional relevant MeSH terms:
Bacterial Infections

ClinicalTrials.gov processed this record on October 23, 2014