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

• ClinicalTrials.gov Identifier: NCT01093521
• Recruitment Status: Completed
• First Posted: March 26, 2010
• Results First Posted: January 12, 2016
• Last Update Posted: November 29, 2022
• Sponsor: University of Washington
• Collaborator: Cystic Fibrosis Foundation
• Information provided by (Responsible Party): Chris Goss, University of Washington

Tracking Information

• First Submitted Date: March 24, 2010
• First Posted Date: March 26, 2010
• Results First Submitted Date: September 15, 2014
• Results First Posted Date: January 12, 2016
• Last Update Posted Date: November 29, 2022
• Study Start Date: April 2010
• Actual Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 8, 2015)

• Pharmacokinetic Assessment of a 5 Day Infusion of Gallium Nitrate (IV Ganite®) [ Time Frame: 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.
• Number of Serious Adverse Events [ Time Frame: 56 days from starting dose ]
  Safety as measured by serous adverse events
• Number of Events When Study Drug Infusion Was Stopped Early [ Time Frame: 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

Original Primary Outcome Measures (submitted: March 25, 2010)

Pharmacokinetic, safety, and tolerability assessment of a 5 day infusion of gallium nitrate (IV Ganite®) [ Time Frame: 28 days ]

To assess the pharmacokinetics 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. 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.

Current Secondary Outcome Measures (submitted: December 8, 2015)

• Change in Spirometry From Baseline to Day 8 [ Time Frame: 8 days ]
  Change in spirometry as measured by FEV1 in liters from baseline to day 8
• Change in Lung Function From Baseline to Day 15 [ Time Frame: 15 days from starting dose ]
  Change in FEV1 in liters from baseline to day 15
• Change in Spirometry From Baseline to Day 28 [ Time Frame: 28 days from starting dose ]
  Change in lung function as measured by FEV1 in liters from baseline to day 28
• Change in Spirometry From Baseline to Day 56 [ Time Frame: 56 days from starting dose ]
  Change in lung function as measured by FEV1 in liters from baseline to day 56
• Change in Spirometry as Measured by FVC From Baseline to Day 8 [ Time Frame: 8 days from starting dose ]
  Change from baseline in lung function assessed by FVC in liters after treatment with IV Ga at day 8
• Change in P. Aeruginosa Density From Baseline to Day 8 [ Time Frame: 8 days from starting dose ]
  Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 8
• Change in Sputum P. Aeruginosa Density From Baseline to Day 15 [ Time Frame: 15 days from starting dose ]
  Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 15
• Change in P. Aeruginosa Density From Baseline to Day 56 [ Time Frame: 56 days from starting dose ]
  Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 56

Original Secondary Outcome Measures (submitted: March 25, 2010)

Change in spirometry, change in sputum microbiology [ Time Frame: 28 days ]

Change in spirometry from baseline to day 8, from baseline to day 15 and from baseline to day 28. Change from baseline in FEV1 after treatment with IV Ga. Change from baseline in FVC after treatment with IV Ga. Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 8, from baseline to day 15, and from baseline to day 28

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients
• Official Title: A Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients

Brief Summary

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)

Detailed Description

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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Cystic Fibrosis

Intervention

• Drug: 100 mg/m2 dose
  5 day infusion of gallium nitrate (IV Ganite®) at a dose of 100 mg/m2/day
  Other Names:

  • Ganite®
  • gallium nitrate
• Drug: 200 mg/m2 dose
  5 day infusion of gallium nitrate (IV Ganite®) at 200 mg/m2/day
  Other Names:

  • Ganite®
  • gallium nitrate

Study Arms

• Experimental: 100 mg/m2 dose
  Five day continuous IV Gallium Nitrate (Ganite®) infusion at 100 mg/m2
  Intervention: Drug: 100 mg/m2 dose
• Experimental: 200 mg/m2 dose
  Five day continuous IV Gallium Nitrate (Ganite®) infusion at 200 mg/m2
  Intervention: Drug: 200 mg/m2 dose

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 14, 2012): 20
• Original Estimated Enrollment (submitted: March 25, 2010): 18
• Actual Study Completion Date: August 31, 2013
• Actual Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01093521
• Other Study ID Numbers: 35876; US FDA 5R01FD003704 ( Other Grant/Funding Number: FDA )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Chris Goss, University of Washington
• Original Responsible Party: Christopher H. Goss, MD, MSc - Principal Investigator, University of Washington
• Current Study Sponsor: University of Washington
• Original Study Sponsor: Same as current
• Collaborators: Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Christopher H Goss, MD, MSc; University of Washington

• PRS Account: University of Washington
• Verification Date: October 2022