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

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01897779
• Other study ID #: Rempex 501
• Status: Completed
• Phase: Phase 1
• First received: July 9, 2013
• Last updated: April 27, 2014
• Start date: July 2013
• Est. completion date: February 2014

Study information

• Verified date: April 2014
• Source: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Infections
• Healthy Volunteers

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Australia	CMAX	Adelaide	South Australia

Sponsors (1)

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

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety from baseline through the end of the study	Number of patients with adverse events; assessed by patient reporting, collection of vital signs, ECGs and absolute values and changes over time of hematology, chemistry and urinalysis.	Study Day 1 to Day 14	No
Secondary	Composite of PK parameters RPX7009, RPX2014, combination of RPX7009 and RPX2014 & placebo following single and multiple dose administration.	Plasma AUC0-t, AUC0-inf, Cmax, and Tmax.	Study Day1 to Day 14	No