Phase I/II Evaluation of the Safety, Pharmacokinetics, and Preliminary Effectiveness of Nikkomycin Z in the Treatment of Patients With Uncomplicated Coccidioides Pneumonia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Concentration of Nikkomycin Z in the Blood Over Time (AUC)
研究概览
简要总结
The purpose of this study is to determine if nikkomycin Z is safe when administered at different dose levels for 14 days. The study will also determine blood levels and urinary excretion of nikkomycin Z in relation to dose administered. Patients with mild forms of Valley Fever pneumonia will be eligible to participate and will be allocated to receive treatment with nikkomycin Z (various doses) or a placebo. A secondary goal of this study is to evaluate the effectiveness and dose response of nikkomycin Z in an exploratory analysis.
详细描述
Every year there are 50,000 new U.S. cases of coccidioidomycosis (Valley Fever). The majority of these illnesses occur as a result of endemic exposure in Arizona and California. The benefits of antifungal therapy for uncomplicated disease are not currently established. Current therapies for serious and complicated forms of coccidioidomycosis are only partially effective and in themselves are unable to eradicate the fungus from sites of infection, commonly resulting in breakthrough infection and/or relapse. Nikkomycin Z is effective in the mouse model and results in improved microbiological response over fluconazole.
The goals of this study include: 1) Evaluating the safety and tolerance of nikkomycin Z following administration of multiple doses (50 mg Q 12 h to 750 mg Q 8 h) for two week and 2) Evaluating the pharmacokinetics of nikkomycin Z after single and multiple doses in relationship to dose. The study will include patients with uncomplicated Coccidioides pneumonia (mild illness) which will allow exploratory analysis of efficacy and dose response based on biomarkers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years and <= 50 years
- •Male or Female (if female, must have a negative pregnancy test and agree to use an acceptable contraception method)
- •Able to understand study and give written informed consent
- •Have a respiratory illness with at least one of the following: Cough, chest pain dyspnea or tachypnea, sputum production, or fever/chills/night sweats
- •Have a new or suspected new pulmonary infiltrate on Chest X-ray
- •Have a positive coccidioidal serology by EIA or immunodiffusion
排除标准
- •Patients under the age of 18 years or over 50 years
- •Patients with a prior history of confirmed coccidioidal infection
- •Laboratory diagnosis of another etiology for the inclusion-defining illness
- •Inability to comprehend study and provide informed consent
- •History of or current evidence of major organ disease
- •Concomitant use of prednisone and other corticosteroids not permitted
- •Concomitant immunosuppressive therapy is not permitted
- •Concomitant antibacterial therapy is not permitted
研究组 & 干预措施
A - First dose level (n=5)
nikkomycin Z 50 mg BID x 14 days
干预措施: nikkomycin Z (Drug)
B - Second Dose Level (n=10)
nikkomycin Z nikkomycin Z 250 mg BID x 14 days
干预措施: nikkomycin Z (Drug)
C - Third Dose Level (n=10)
nikkomycin Z 500 mg BID x 14 days
干预措施: nikkomycin Z (Drug)
D - Fourth Dose Level (n=5)
nikkomycin Z 750 BID x 14 days
干预措施: nikkomycin Z (Drug)
Placebo
placebo BID x 14 days
干预措施: Placebo (Drug)
结局指标
主要结局
Concentration of Nikkomycin Z in the Blood Over Time (AUC)
时间窗: 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2 , 3, 4, 6, 8 and 12 h hours post-dose on Day 1 and Day 14
Highest Concentration of Nikkomycin Z in the Blood (Cmax)
时间窗: 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2 , 3, 4, 6, 8 and 12 h hours post-dose on Day 1 and Day 14
次要结局
未报告次要终点