Clinical trial NCT01897779: Safety, Tolerability, Pharmacokinetics of Intravenous RPX2014 and RPX7009 in Healthy Adult Subjects
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple Ascending-dose Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous RPX2014 and RPX7009 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: 2013-07-12
Enrollment: 94
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 studied in combination with a carbapenem (RPX2014) 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 (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.

Eligibility criteria: 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).

Primary outcomes:
measure: Safety from baseline through the end of the study
timeFrame: Study Day 1 to Day 14
Secondary outcomes:
measure: Composite of PK parameters RPX7009, RPX2014, combination of RPX7009 and RPX2014 & placebo following single and multiple dose administration.
timeFrame: Study Day1 to Day 14
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX
state: South Australia
Study officials:
affiliation: Sponsor GmbH
name: Jeffery Loutit
role: STUDY_DIRECTOR
References:
citation: Rubino CM, Bhavnani SM, Loutit JS, Morgan EE, White D, Dudley MN, Griffith DC. Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Vaborbactam and Meropenem Alone and in Combination following Single and Multiple Doses in Healthy Adult Subjects. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e02228-17. doi: 10.1128/AAC.02228-17. Print 2018 Apr.