A Study to Assess the Safety, Tolerability and Pharmacokinetics of NXL104 Alone and in Combination With Ceftazidime Administered as Single and Repeated Intravenous Doses in Healthy Japanese Subjects

Study Overview
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Brief Summary
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This is a single and multiple dose study in healthy male and female (of non-childbearing potential) Japanese volunteers, to assess the safety, tolerability, and blood and urine drug levels of intravenous (IV) NXL104 alone and when given in combination with ceftazidime.

Official Title
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A Phase I, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety, Tolerability and Pharmacokinetics of NXL104 Alone and in Combination With Ceftazidime Administered as Single and Repeated Intravenous Doses in Healthy Japanese Subjects

Conditions
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Healthy Male and Female Japanese Volunteers

Intervention / Treatment
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* Drug: NXL104
* Drug: CAZ104
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be considered as 'Japanese', both of the volunteer's parents, and all grandparents must be Japanese. The volunteer must have been born in Japan, have a valid Japanese passport and must not have lived outside Japan for more than 5 years Have a body mass index (BMI) between 17 and 27 kg/m2 inclusive and weigh at least 45 kg and no more than 100 kg. Females must not be lactating, and must be of non-childbearing potential (post-menopausal at least 12 months or documented irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation Exclusion Criteria: History or presence of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs Symptoms of a clinically significant illness in the 3 months before the study History of hypersensitivity (eg, anaphylaxis), serious allergy, or any serious reaction to carbapenem, cephalosporins, or other β-lactam antibiotics Use within 14 days prior to the first study dose of any over-the-counter (including St. John's Wort or any herbal products) or prescription medication Smoker of more than 5 cigarettes/day or equivalent use of nicotine products during the previous 3 months

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NXL104<br>Six Japanese subjects to receive single and repeated 500 mg IV infusions of NXL104 | Drug: NXL104<br>* IV Solution<br>|
| Placebo Comparator: Placebo<br>Three Japanese subjects to receive placebo IV doses | Drug: Placebo<br>* IV saline<br>|
| Experimental: Ceftazidime NXL104 (CAZ104)<br>Six Japanese subjects to receive single and repeated IV infusions of 500 mg NXL104 with 2000 mg ceftazidime | Drug: CAZ104<br>* IV Solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events will be monitored as a measure of safety and tolerability |  | A range of 12 days | 
| Vital signs, physical examinations, clinical laboratory tests, 12 lead electrocardiogram (ECG) and digital ECG will be assessed as a measure of safety and tolerability |  | A range of 12 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pharmacokinetic parameters of plasma of NXL104 alone or in combination with ceftazidime |  | Range of 8 days | 
| The pharmacokinetic parameters of urine of NXL104 alone or in combination with ceftazidime |  | Range of 8 days | 
| The level of intestinal bacterial flora of NXL104 alone or in combination with ceftazidime |  | Range of 12 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NXL104, ceftazidime, CAZ104, Healthy Japanese volunteers, Phase 1, Single and Multiple Dose Study