Safety, Tolerability, Pharmacokinetics of Intravenous RPX2003 (Biapenem) 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:
NCT01702649
First received: September 25, 2012
Last updated: November 29, 2012
Last verified: November 2012
  Purpose

RPX2003 (biapenem) is being studied in combination with a beta-lactamase inhibitor to treat bacterial infections, including those due to multi-drug resistant bacteria.


Condition Intervention Phase
Healthy Volunteers
Bacterial Infections
Drug: RPX2003 (Biapenem)
Drug: Placebo
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 of Intravenous RPX2003 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 13. ] [ 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 RPX2003 & placebo following single dose administration. [ Time Frame: Part 1A Study Day 1 to 3. ] [ Designated as safety issue: No ]
    plasma AUC0-t, AUC0-inf, Cmax, and Tmax.

  • Composite of PK parameters RPX2003 & placebo following multiple dose administration. [ Time Frame: Part 1B Day 4 to 12 ] [ Designated as safety issue: No ]
    plasma AUC0-t, AUC0-inf, Cmax, and Tmax.


Enrollment: 36
Study Start Date: August 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RPX2003 (Biapenem)
Single and multiple dose of RPX2003 (Biapenem).
Drug: RPX2003 (Biapenem)

Six (6) cohorts of 3 active or 8 subjects of 6 active are planned for evaluation.

Single dose followed by multiple dose, three times a day.

Placebo Comparator: Normal Saline
Single and multiple doses of normal saline.
Drug: Placebo

Six (6) cohorts of 1 placebo or 8 subjects of 2 placebo are planned for evaluation.

Single dose followed by multiple dose, three times a day.


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 of biapenem, administered alone, 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 compounds related to the study drug (e.g. beta-lactam antibiotics such as penicillins, carbapenems, etc).
  • History of seizures (e.g., epilepsy).
  • 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.
  • 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: NCT01702649

Locations
United States, Arizona
Celerion
Tempe, Arizona, United States, 85283
Sponsors and Collaborators
Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Investigators
Study Director: Jeff Loutit, MBChB Sponsor GmbH
  More Information

No publications provided

Responsible Party: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
ClinicalTrials.gov Identifier: NCT01702649     History of Changes
Other Study ID Numbers: Rempex 401
Study First Received: September 25, 2012
Last Updated: November 29, 2012
Health Authority: 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 September 16, 2014