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

Rempex Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers; Bacterial Infections

Treatments: Drug: RPX7009; Drug: Normal saline; Drug: Biapenem

Study type: Interventional

Funder types: Industry

Identifiers

NCT01772836

Rempex 403

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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30 participants in 4 patient groups, including a placebo group

Normal saline

Placebo Comparator group

Description:

Single and multiple dose of normal saline

Treatment:

Drug: Normal saline

Single dose IV of biapenem or RPX7009

Experimental group

Description:

Single dose IV infusion of biapenem or RPX7009

Treatment:

Drug: Biapenem

Drug: RPX7009

Single dose of biapenem or RPX7009

Experimental group

Description:

Single IV dose of biapenem or RPX7009 (for those on active drug, this will be the drug not given in the first IV treatment)

Treatment:

Drug: Biapenem

Drug: RPX7009

Biapenem and RPX7009 in combination

Experimental group

Description:

Single dose followed by a multiple dose of biapenem and RPX7009 in combination

Treatment:

Drug: Biapenem

Drug: RPX7009