A Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients
A Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients
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)
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.

 Secondary efficacy assessments will be based on changes in lung function and sputum P.
 aeruginosa density in sputum.

 Total duration of subject participation will be five weeks. Total duration of the study is
 expected to be 20 months.
Inclusion Criteria:

 1. Adult male or female, between 18 and 55 years of age

 2. Documented chronic colonization with Pseudomonas Aeruginosa (Pa)

 3. Confirmed diagnosis of CF:

 1. Documented history of > 60 mmol/L chloride concentration in pilocarpine sweat
 chloride test And/Or

 2. Genotype with two identifiable mutations consistent with CF, accompanied by one
 or more phenotypic features consistent with diagnosis of CF

 4. Forced expiratory volume in the first second (FEV1) ≥ 30% of predicted value

 5. Able to expectorate sputum

 6. Serum liver function tests ≤ 2.5 x upper limit of normal

 7. Serum urea nitrogen (BUN) and creatinine ≤ 1.5 x upper limit of normal

 8. Serum creatinine ≤ 2.0 mg/dl

 9. Hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/mm3, and white blood cells (WBC) ≥ 4,500/mm3
 and ≤ 15,000/mm3

 10. Ionized calcium ≥ the lower limit of normal

 11. Able to understand and sign the informed consent document, communicate with the
 Investigator, and comply with the requirements of the protocol

 12. If female and of childbearing potential, must have a negative pregnancy test on Day 1
 prior to receiving study drug

 13. If female and of childbearing potential, is willing to use adequate contraception, as
 determined by the investigator, for the duration of the study

 Exclusion Criteria:

 1. Acute pulmonary exacerbation requiring antibiotic intervention within 2 weeks prior to
 screening

 2. Osteoporosis defined as the most recent dexa scan within the prior 5 years with a
 T-score ≤ -2.5

 3. Pregnant or lactating female

 4. Known sensitivity to gallium

 5. Use of biphosphonates

 6. Use of any investigational drug and/or participated in any clinical trial within 3
 months prior to screening