Safety, Tolerability, Pharmacokinetics of Intravenous RPX2003 (Biapenem) in Healthy Adult Subjects

Healthy Volunteers Clinical Trial

Official title:

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Single- and Multiple-Dose Study of the Safety, Tolerability, Pharmacokinetics of Intravenous RPX2003 in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01702649
• Other study ID #: Rempex 401
• Status: Completed
• Phase: Phase 1
• First received: September 25, 2012
• Last updated: November 29, 2012
• Start date: August 2012
• Est. completion date: November 2012

Study information

• Verified date: November 2012
• Source: Rempex Pharmaceuticals (a wholly owned subsidiary of The Medicines Company)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RPX2003 (biapenem) is being studied in combination with a beta-lactamase inhibitor 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 (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 of biapenem, administered alone, in healthy adult subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 compounds related to the study drug (e.g. beta-lactam antibiotics such as penicillins, carbapenems, etc).

• History of seizures (e.g., epilepsy).

• 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.

• Blood donation or significant blood loss (i.e., > 500 mL) within 56 days prior to Day 1.

• 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:
• RPX2003 (Biapenem)
Six (6) cohorts of 3 active or 8 subjects of 6 active are planned for evaluation. Single dose followed by multiple dose, three times a day.
• Placebo
Six (6) cohorts of 1 placebo or 8 subjects of 2 placebo are planned for evaluation. Single dose followed by multiple dose, three times a day.

Locations

Country	Name	City	State
United States	Celerion	Tempe	Arizona

Sponsors (1)

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

Country where clinical trial is conducted

United States, 

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 13.	No
Secondary	Composite of PK parameters RPX2003 & placebo following single dose administration.	plasma AUC0-t, AUC0-inf, Cmax, and Tmax.	Part 1A Study Day 1 to 3.	No
Secondary	Composite of PK parameters RPX2003 & placebo following multiple dose administration.	plasma AUC0-t, AUC0-inf, Cmax, and Tmax.	Part 1B Day 4 to 12	No