Safety Study of Intravenous Ertapenem in Combination With Zidebactam (WCK 6777)
Condition: Bacterial Infection
MeSH terms: Bacterial Infections
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Ertapenem; Placebo; WCK 6777; Zidebactam
Intervention type(s): Drug; Other; Drug; Drug
Intervention description(s): A 1-beta methyl-carbapenem that is structurally related to beta-lactam antibiotics; Placebo; A combination of ertapenem (ERT) and zidebactam (ZID); A betaß-lactamase inhibitor and betaß-lactam enhancer from the diazabicyclooctane (DBO) class
Intervention MeSH terms: Ertapenem
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Double-blind; Intravenous Ertapenem; Phase 1; Safety; Zidebactam (WCK 6777)