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

NCT ID: NCT01897779

Last Updated: 2014-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 94 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31
• Study Completion Date: 2014-02-28

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.

Conditions

Healthy Volunteers; Bacterial Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Single and multiple dose of RPX7009

Single and multiple dose of RPX7009

Group Type: EXPERIMENTAL

RPX7009

Intervention Type: DRUG

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation in cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Single and multiple dose of RPX2014

Single and multiple dose of RPX2014

Group Type: EXPERIMENTAL

RPX2014

Intervention Type: DRUG

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation for cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Normal Saline

Single and multiple dose of normal saline

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation for cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Combination RPX7009 and RPX2014

Single and Multiple dose of Combination RPX7009 and RPX2014

Group Type: EXPERIMENTAL

Combination RPX7009 and RPX2014

Intervention Type: DRUG

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation in cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Interventions

RPX7009

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation in cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Intervention Type: DRUG

RPX2014

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation for cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Intervention Type: DRUG

Placebo

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation for cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Intervention Type: DRUG

Combination RPX7009 and RPX2014

Two (2) groups of 15 subjects (12 active and 3 placebo) are planned for evaluation in cohort 1. Cohorts 2-5, 14 subjects (11 active and 3 placebo) are planned for evaluation in each cohort. 14 subjects (12 active and 2 placebo) are planned for evaluation in cohort 6.

Intervention Type: DRUG

Other Intervention Names

(beta-lactamase inhibitor); Normal saline

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffery Loutit

Role: STUDY_DIRECTOR

Sponsor GmbH

Locations

CMAX

Adelaide, South Australia, Australia

Countries

Australia

References

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.

Reference Type: DERIVED

PMID: 29437614 (View on PubMed)

Other Identifiers

Rempex 501

Identifier Type: -

Identifier Source: org_study_id