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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cystic Fibrosis Foundation Therapeutics
Information provided by (Responsible Party):
Chris Goss, University of Washington
ClinicalTrials.gov Identifier:
NCT01093521
First received: March 24, 2010
Last updated: December 8, 2015
Last verified: December 2015
  Purpose

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)


Condition Intervention Phase
Cystic Fibrosis
Drug: 100 mg/m2 dose
Drug: 200 mg/m2 dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: Yes ]
    Safety as measured by serous adverse events

  • Number of Events When Study Drug Infusion Was Stopped Early [ Time Frame: 6 days from starting dose ] [ Designated as safety issue: Yes ]
    Tolerability as measured by adverse events of a 5 day continuous infusion of IV Gallium as assessed by stopping study drug infusion


Secondary Outcome Measures:
  • Change in Spirometry From Baseline to Day 8 [ Time Frame: 8 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 56


Enrollment: 20
Study Start Date: April 2010
Estimated Study Completion Date: September 2018
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 100 mg/m2 dose
Five day continuous IV Gallium Nitrate (Ganite®) infusion at 100 mg/m2
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
Experimental: 200 mg/m2 dose
Five day continuous IV Gallium Nitrate (Ganite®) infusion at 200 mg/m2
Drug: 200 mg/m2 dose
5 day infusion of gallium nitrate (IV Ganite®) at 200 mg/m2/day
Other Names:
  • Ganite®
  • gallium nitrate

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01093521

Locations
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242-1083
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21201
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
Cystic Fibrosis Foundation Therapeutics
Investigators
Principal Investigator: Christopher H Goss, MD, MSc University of Washington
  More Information

No publications provided

Responsible Party: Chris Goss, Associate Professor, University of Washington
ClinicalTrials.gov Identifier: NCT01093521     History of Changes
Other Study ID Numbers: 35876-D  US FDA 5R01FD003704 
Study First Received: March 24, 2010
Results First Received: September 15, 2014
Last Updated: December 8, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Washington:
IV Gallium
Gallium
Ganite
Cystic Fibrosis
Gallium Infusion

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Digestive System Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Lung Diseases
Pancreatic Diseases
Pathologic Processes
Respiratory Tract Diseases
Gallium nitrate
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on February 11, 2016