Clinical trial NCT01291602: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Male and Female Japanese Volunteers
Keywords: NXL104
ceftazidime
CAZ104
Healthy Japanese volunteers
Phase 1
Single and Multiple Dose Study
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-02-08
Enrollment: 15
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Adverse events will be monitored as a measure of safety and tolerability
timeFrame: A range of 12 days
measure: Vital signs, physical examinations, clinical laboratory tests, 12 lead electrocardiogram (ECG) and digital ECG will be assessed as a measure of safety and tolerability
timeFrame: A range of 12 days
Secondary outcomes:
measure: The pharmacokinetic parameters of plasma of NXL104 alone or in combination with ceftazidime
timeFrame: Range of 8 days
measure: The pharmacokinetic parameters of urine of NXL104 alone or in combination with ceftazidime
timeFrame: Range of 8 days
measure: The level of intestinal bacterial flora of NXL104 alone or in combination with ceftazidime
timeFrame: Range of 12 days
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
city: Baltimore
country: United States
facility: Research Site
state: Maryland
Study officials:
affiliation: AstraZeneca
name: Paul Newell, MD
role: STUDY_DIRECTOR
affiliation: PAREXEL Early Phase/California Clinical Trials Medical Group
name: Mark Yen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.