MAD Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Intravenous Zidebactam in Healthy Adults

Study Overview
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Brief Summary
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Study to evaluate the safety and tolerability of multiple escalating doses of intravenous (IV) Zidebactam in healthy adult human subjects.

Detailed Description
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A double-blind, placebo-controlled study where healthy adult subjects will be randomly assigned to receive either of the investigational products (Zidebactam or placebo) in 2 multiple ascending dose (MAD) cohorts. Primary Objective: to evaluate the safety and tolerability of multiple escalating doses of intravenous (IV) zidebactam in healthy adult human subjects. Secondary Objective: to evaluate the pharmacokinetics (PK) of multiple escalating doses of IV zidebactam in healthy adult human subjects.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Escalating Doses of Intravenous Zidebactam in Healthy Adult Human Subjects

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: 3 g or 6 g Zidebactam
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index of 18 to 30 kg/m2 (both inclusive) calculated as weight (kg)/height (m2). Medical history without any major pathology/surgery in the last 6 months prior to screening. All values of hematology, serum chemistry, coagulation, and urinalysis showing no clinically significant deviations from normal as judged by the Principal Investigator. Resting supine blood pressure of 90 to 139 (systolic)/40 to 89 (diastolic) mmHg and a resting pulse rate of 40 to 100 beats per minute. Calculated creatinine clearance ≥80 mL/min (Cockcroft-Gault method). Computerized 12-lead ECG recording without signs of clinically significant pathology and showing no clinically significant deviation as judged by the Principal Investigator. Exclusion Criteria: History of clinically significant food or drug allergy, including known hypersensitivity to β lactam drugs or other related drugs. History of Clostridium difficile induced diarrhea or infection within 1 year before screening Consumed more than 28 units of alcohol per week at any time in the 6 months before investigational product administration History/evidence of clinically relevant pathology related to the cardiovascular system, central nervous system, respiratory tract, gastrointestinal tract, endocrinology, immunology, hematology or any other systemic disorder/major surgeries, that in the opinion of the Principal Investigator would confound the subject's participation and follow-up in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: 3 g or 6 g of Zidebactam<br>Cohort 1 (Zidebactam): 3 g of Zidebactam (1 g every 8 hours [q8h]) (n=8) IV infusions administered over 60 minutes. Cohort 2 (Zidebactam or placebo): 6 g of Zidebactam (2 g q8h) (n=8) IV infusions administered over 60 minutes. | Drug: 3 g or 6 g Zidebactam<br>* IV for over a duration of 60 minutes<br>* Other names: WCK 5107;|
| Placebo Comparator: Placebo<br>Cohort 1: Placebo every 8 hours [q8h] (n=2) IV infusions administered over 60 minutes. Cohort 2: Placebo every q8h (n=2) IV infusions administered over 60 minutes. | Drug: Placebo<br>* IV matching the Investigational drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability will be evaluated by reported AEs, clinical observations, vital signs measurements, and physical examination findings. |  | 14 days | 
| Safety and tolerability will be evaluated by 12-lead safety ECG results and clinical laboratory test results |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters -maximum plasma concentration will be evaluated. |  | 7 days | 
| Pharmacokinetic parameters- area under the plasma concentration-time curve from zero (pre-dose) to 8 hours will be evaluated. |  | 7 days | 
| Pharmacokinetic parameters- terminal half life etc will be evaluated |  | 7 days |