Clinical trial NCT01772836: Safety Study of Intravenous Biapenem (RPX2003) and RPX7009 Given Alone and in Combination
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Bacterial Infections
Lead sponsor: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
Sponsor class: INDUSTRY
First posted: 2013-01-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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 and pharmacodynamics of Intravenous Biapenem and RPX7009, administered alone and in combination in healthy adult subjects.

Eligibility 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 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).

Primary outcomes:
measure: Safety from baseline to the end of the study
timeFrame: Day 1 - Day 17
Secondary outcomes:
measure: Composite of Pharmacokinetic (PK) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration.
timeFrame: Day 1 - Day 14
measure: Composite of Pharmacodynamic (PD) parameters of RPX7009, biapenem & the combination following ascending single and multiple dose administration.
timeFrame: Days 1-14
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
Study officials:
affiliation: Sponsor GmbH
name: Jefferey Loutit, MBChB
role: STUDY_DIRECTOR
References: