Safety, Tolerability, Pharmacokinetics of Intravenous RPX2014 and RPX7009 in Healthy Adult Subjects

Rempex Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers; Bacterial Infections

Treatments: Drug: Combination RPX7009 and RPX2014; Drug: RPX7009; Drug: Placebo; Drug: RPX2014

Study type: Interventional

Funder types: Industry

Identifiers

NCT01897779

Rempex 501

Details and patient eligibility

About

RPX7009 (beta-lactamase inhibitor) is being studied in combination with a carbapenem (RPX2014) 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 (RPX2014) 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 intravenous RPX2014 and RPX7009, administered alone and in combination, in healthy adult subjects.

Enrollment: 94 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy adult males and females, 18 to 55 years of age (inclusive) at the time of screening.
2. Body mass index (BMI) ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive).
3. Medically healthy with clinically insignificant screening results (e.g., laboratory profiles, medical histories, ECGs, physical examination) as deemed by the PI.
4. Non-tobacco/nicotine-containing product users for a minimum of Dose Study 6 months prior to Day 1.
5. Voluntarily consent to participate in the study.
6. Sexually abstinent or agree to use two approved methods of contraception.

Exclusion criteria

1. History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease.
2. Positive urine drug/alcohol testing at screening or check-in (Day -1).
3. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
4. History or presence of alcoholism or drug abuse within the 2 years prior to Day 1.
5. 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.
6. Blood donation or significant blood loss (i.e., > 500 mL) within 56 days prior to Day 1.
7. Plasma donation within 7 days prior to Day 1.
8. Participation in another investigational clinical trial within 30 days prior to Day 1.
9. 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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94 participants in 4 patient groups, including a placebo group

Single and multiple dose of RPX7009

Experimental group

Description:

Single and multiple dose of RPX7009

Treatment:

Drug: RPX7009

Single and multiple dose of RPX2014

Experimental group

Description:

Single and multiple dose of RPX2014

Treatment:

Drug: RPX2014

Normal Saline

Placebo Comparator group

Description:

Single and multiple dose of normal saline

Treatment:

Drug: Placebo

Combination RPX7009 and RPX2014

Experimental group

Description:

Single and Multiple dose of Combination RPX7009 and RPX2014

Treatment:

Drug: Combination RPX7009 and RPX2014