Clinical Trials Directory

Trials / Completed

CompletedNCT05645757

Safety Study of Intravenous Ertapenem in Combination With Zidebactam (WCK 6777)

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous Ertapenem in Combination With Zidebactam (WCK 6777) In Healthy Adult Subjects

Status
Completed
Phase
Phase 1
Study type
Interventional
Enrollment
54 (actual)
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) · NIH
Sex
All
Age
18 Years – 45 Years
Healthy volunteers
Accepted

Summary

This is a Phase 1, single center study to investigate the safety, tolerability, and pharmacokinetics (PK) of three dose-level groups of WCK 6777 (ERT and ZID combination), and two dose-level groups of ERT alone and ZID (WCK 5107) alone in 52 healthy adult male and female subjects aged 18 to 45 years old (both inclusive). Seven treatment cohorts will be evaluated in this study. WCK 6777 will be evaluated in three cohorts - Cohorts 1, 4 and 7- of 8 subjects each (6 study drug combinations and 2 placebos); ERT will be evaluated alone in two cohorts - Cohorts 2 and 5- of 8 subject each (6 ERT and 2 placebos); and ZID will be evaluated in two cohorts, Cohorts 3 and 6, of 6 subjects each (all ZID). The study will be placebo-controlled and double-blinded in all cohorts except Cohorts 3 and 6. No placebo subjects are included in standalone ZID cohorts, since adequate safety data for higher doses of ZID alone in comparison with placebo are available from completed Phase 1 studies of WCK 5107 (ZID) alone and the ZID-only arms of WCK 5222 (cefepime + ZID) studies. The primary objective is to assess the safety and tolerability of three dose-escalating regimens of WCK 6777 ( ERT and ZID combination) and two-dose escalating regimens of standalone ERT or ZID following single daily doses for 7 days in healthy adult subjects.

Detailed description

This is a Phase 1, single center study to investigate the safety, tolerability, and pharmacokinetics (PK) of three dose-level groups of WCK 6777 (ERT and ZID combination), and two dose-level groups of ERT alone and ZID (WCK 5107) alone in 52 healthy adult male and female subjects aged 18 to 45 years old (both inclusive). Seven treatment cohorts will be evaluated in this study. WCK 6777 will be evaluated in three cohorts - Cohorts 1, 4 and 7- of 8 subjects each (6 study drug combinations and 2 placebos); ERT will be evaluated alone in two cohorts - Cohorts 2 and 5- of 8 subject each (6 ERT and 2 placebos); and ZID will be evaluated in two cohorts, Cohorts 3 and 6, of 6 subjects each (all ZID). The study will be placebo-controlled and double-blinded in all cohorts except Cohorts 3 and 6. No placebo subjects are included in standalone ZID cohorts, since adequate safety data for higher doses of ZID alone in comparison with placebo are available from completed Phase 1 studies of WCK 5107 (ZID) alone and the ZID-only arms of WCK 5222 (cefepime + ZID) studies. In each cohort, either study drugs alone or their combination will be administered by a single intravenous infusion (IV) of 100 mL daily for 7 consecutive days in Cohort 1 or 250 mL daily for 7 consecutive days in Cohorts 2 to 7. For each treatment cohort, however, the dose will be progressively escalated from 1 g/daily to 2 g/daily and to 3 g/daily, and the duration of infusion time increased from 30 min to 1 h and to 2 h over the course of the study. In Cohort 1, WCK 6777 2 g (ERT 1 g/daily combined with ZID 1 g/daily) will be administered in 30 (±5) minutes (min); in Cohort 2 (ERT 2 g/daily), Cohort 3 (ZID 2 g/daily), and Cohort 4 (WCK 6777 4 g \[ERT 2 g/daily combined with ZID 2 g/daily\]) the study drug(s) will be administered in 60 (±10) min, and in Cohort 5 (ERT 3 g/daily), Cohort 6 (ZID 3 g daily) and Cohort 7 (WCK 6777 6 g \[ERT 3 g/daily combined with ZID 3 g/daily\]), the study drug(s) will be administered in 120 (±10) min. The primary objective is to assess the safety and tolerability of three dose-escalating regimens of WCK 6777 ( ERT and ZID combination) and two-dose escalating regimens of standalone ERT or ZID following single daily doses for 7 days in healthy adult subjects. The secondary objective is to characterize the PK profiles in plasma (total \& free) and in urine of three dose-escalating regimens of WCK 6777 (ERT and ZID combination) and two dose-escalating regimens of standalone ERT or ZID following a single initial dose on Day 1 and after single daily doses for 7 days in healthy adult subjects.

Conditions

Interventions

TypeNameDescription
DRUGErtapenemA 1-beta methyl-carbapenem that is structurally related to beta-lactam antibiotics
OTHERPlaceboPlacebo
DRUGWCK 6777A combination of ertapenem (ERT) and zidebactam (ZID)
DRUGZidebactamA betaß-lactamase inhibitor and betaß-lactam enhancer from the diazabicyclooctane (DBO) class

Timeline

Start date
2023-04-19
Primary completion
2023-11-03
Completion
2023-11-03
First posted
2022-12-09
Last updated
2025-01-20
Results posted
2024-12-05

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT05645757. Inclusion in this directory is not an endorsement.