A Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- Number of Serious Adverse Events
研究概览
简要总结
The purpose of this research study is to test the pharmacokinetics, safety, and tolerability of an intravenous infusion of a drug called Ganite (gallium nitrate) in patients with cystic fibrosis. We want to see this drug is safe and tolerable and to see if high levels of the drug are found in the sputum.
Funding Source - Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD)
详细描述
This is a two center pharmacokinetic and safety dosing study of IV gallium nitrate (Ganite®) in cystic fibrosis (CF) patients. Eighteen subjects are planned. Each subject will be administered a single 5-day infusion of study medication (one of 2 doses). No placebo is used. Each subject will receive 5 days of continuous infusion of the experimental treatment. There will be two dosing cohorts (cohort 1: 100 mg/m2/day and cohort 2: 200 mg/m2/day). Cohort 2 will begin enrollment only after Data Safety Monitoring Committee (DSMC) safety review and approval of cohort 1 data. Study visits occur at baseline (day 1), day 3 (visit 2), day 6 (visit 3), day 8 (visit 4), day 14 (visit 5), day 28 (visit 6), and day 56 (visit 7).
Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study.
The following treatment regimens will be used:
• Experimental treatment continuous infusion of gallium nitrate at the following doses cohort 1: 100 mg/m2/day and cohort 2: 200 mg/m2/day All subjects who receive at least one dose of study medication will be considered evaluable for safety and efficacy analyses. Incidence of adverse events will be monitored during the trial.
Primary endpoints will be assessment of pharmacokinetic and safety/tolerability data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult male or female, between 18 and 55 years of age
- •Documented chronic colonization with Pseudomonas Aeruginosa (Pa)
- •Confirmed diagnosis of CF:
- •Documented history of > 60 mmol/L chloride concentration in pilocarpine sweat chloride test And/Or
- •Genotype with two identifiable mutations consistent with CF, accompanied by one or more phenotypic features consistent with diagnosis of CF
- •Forced expiratory volume in the first second (FEV1) ≥ 30% of predicted value
- •Able to expectorate sputum
- •Serum liver function tests ≤ 2.5 x upper limit of normal
- •Serum urea nitrogen (BUN) and creatinine ≤ 1.5 x upper limit of normal
- •Serum creatinine ≤ 2.0 mg/dl
- •Hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/mm3, and white blood cells (WBC) ≥ 4,500/mm3 and ≤ 15,000/mm3
- •Ionized calcium ≥ the lower limit of normal
- •Able to understand and sign the informed consent document, communicate with the Investigator, and comply with the requirements of the protocol
- •If female and of childbearing potential, must have a negative pregnancy test on Day 1 prior to receiving study drug
- •If female and of childbearing potential, is willing to use adequate contraception, as determined by the investigator, for the duration of the study
排除标准
- •Acute pulmonary exacerbation requiring antibiotic intervention within 2 weeks prior to screening
- •Osteoporosis defined as the most recent dexa scan within the prior 5 years with a T-score ≤ -2.5
- •Pregnant or lactating female
- •Known sensitivity to gallium
- •Use of biphosphonates
- •Use of any investigational drug and/or participated in any clinical trial within 3 months prior to screening
研究组 & 干预措施
100 mg/m2 dose
Five day continuous IV Gallium Nitrate (Ganite®) infusion at 100 mg/m2
干预措施: 100 mg/m2 dose (Drug)
200 mg/m2 dose
Five day continuous IV Gallium Nitrate (Ganite®) infusion at 200 mg/m2
干预措施: 200 mg/m2 dose (Drug)
结局指标
主要结局
Number of Serious Adverse Events
时间窗: 56 days from starting dose
Safety as measured by serous adverse events
Number of Events When Study Drug Infusion Was Stopped Early
时间窗: 6 days from starting dose
Tolerability as measured by adverse events of a 5 day continuous infusion of IV Gallium as assessed by stopping study drug infusion
Pharmacokinetic Assessment of a 5 Day Infusion of Gallium Nitrate (IV Ganite®)
时间窗: Day 1 at t=1, 2 and 6 hours, Day 3, Day 6 at t= 1, 2, 8, and 12, Day 14 and Day 28
To assess the summed area under the curves of a 5 day infusion of IV Ga from day 1 to day 28 at two doses: 100 mg/m2/day in adult subjects with CF; 200 mg/m2/day in adult subjects with CF. To assess the safety of a 5 day infusion of IV Ga at two doses: 100 mg/m2/day in adult subjects with CF; 200 mg/m2/day in adult subjects with CF. Safety and tolerability of 5 days of treatment with IV administered gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day.
次要结局
- Change in Spirometry From Baseline to Day 8(8 days)
- Change in Lung Function From Baseline to Day 15(15 days from starting dose)
- Change in Spirometry From Baseline to Day 28(28 days from starting dose)
- Change in Spirometry From Baseline to Day 56(56 days from starting dose)
- Change in Spirometry as Measured by FVC From Baseline to Day 8(8 days from starting dose)
- Change in P. Aeruginosa Density From Baseline to Day 8(8 days from starting dose)
- Change in Sputum P. Aeruginosa Density From Baseline to Day 15(15 days from starting dose)
- Change in P. Aeruginosa Density From Baseline to Day 56(56 days from starting dose)
研究者
Chris Goss
Associate Professor
University of Washington