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

Healthy Volunteers Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01772836
• Other study ID #: Rempex 403
• Status: Completed
• Phase: Phase 1
• First received: January 16, 2013
• Last updated: July 9, 2013
• Start date: March 2013
• Est. completion date: March 2013

Study information

• Verified date: July 2013
• Source: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Infections
• Healthy Volunteers

Intervention

Drug:
• RPX7009
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
• Biapenem
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)
• Normal saline
Up to three (3) cohorts of 10 healthy adult subjects (8 active, 2 placebo)

Locations

Country	Name	City	State
Australia	CMAX	Adelaide	South Australia

Sponsors (1)

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

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 - Day 17	No
Secondary	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.	Day 1 - Day 14	No
Secondary	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.	Days 1-14	No