Clinical trial NCT01702649: Safety, Tolerability, Pharmacokinetics of Intravenous RPX2003 (Biapenem) in Healthy Adult Subjects
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
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: 2012-10-08
Enrollment: 36
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: RPX2003 (biapenem) is being studied in combination with a beta-lactamase inhibitor 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 of biapenem, administered alone, 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 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).

Primary outcomes:
measure: Safety from baseline through the end of the study.
timeFrame: Study Day 1 to 13.
Secondary outcomes:
measure: Composite of PK parameters RPX2003 & placebo following single dose administration.
timeFrame: Part 1A Study Day 1 to 3.
measure: Composite of PK parameters RPX2003 & placebo following multiple dose administration.
timeFrame: Part 1B Day 4 to 12
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
affiliation: Sponsor GmbH
name: Jeff Loutit, MBChB
role: STUDY_DIRECTOR
References: