Back to resultsA Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
100 mg/m2 dose
200 mg/m2 dose
Sponsored by
About this trial
This is an interventional other trial for Cystic Fibrosis focused on measuring IV Gallium, Gallium, Ganite, Cystic Fibrosis, Gallium Infusion
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- University of Iowa
- Johns Hopkins University
- University of Washington
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
100 mg/m2 dose
200 mg/m2 dose
Arm Description
Five day continuous IV Gallium Nitrate (Ganite®) infusion at 100 mg/m2
Five day continuous IV Gallium Nitrate (Ganite®) infusion at 200 mg/m2
Outcomes
Primary Outcome Measures
Pharmacokinetic Assessment of a 5 Day Infusion of Gallium Nitrate (IV Ganite®)
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
Safety as measured by serous adverse events
Number of Events When Study Drug Infusion Was Stopped Early
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
Change in spirometry as measured by FEV1 in liters from baseline to day 8
Change in Lung Function From Baseline to Day 15
Change in FEV1 in liters from baseline to day 15
Change in Spirometry From Baseline to Day 28
Change in lung function as measured by FEV1 in liters from baseline to day 28
Change in Spirometry From Baseline to Day 56
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
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
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
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
Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 56
Full Information
NCT ID
NCT01093521
First Posted
March 24, 2010
Last Updated
October 31, 2022
Sponsor
University of Washington
Collaborators
Cystic Fibrosis Foundation
1. Study Identification
Unique Protocol Identification Number
NCT01093521
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
August 31, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
Cystic Fibrosis Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
IV Gallium, Gallium, Ganite, Cystic Fibrosis, Gallium Infusion
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
100 mg/m2 dose
Arm Type
Experimental
Arm Description
Five day continuous IV Gallium Nitrate (Ganite®) infusion at 100 mg/m2
Arm Title
200 mg/m2 dose
Arm Type
Experimental
Arm Description
Five day continuous IV Gallium Nitrate (Ganite®) infusion at 200 mg/m2
Intervention Type
Drug
Intervention Name(s)
100 mg/m2 dose
Other Intervention Name(s)
Ganite®, gallium nitrate
Intervention Description
5 day infusion of gallium nitrate (IV Ganite®) at a dose of 100 mg/m2/day
Intervention Type
Drug
Intervention Name(s)
200 mg/m2 dose
Other Intervention Name(s)
Ganite®, gallium nitrate
Intervention Description
5 day infusion of gallium nitrate (IV Ganite®) at 200 mg/m2/day
Primary Outcome Measure Information:
Title
Pharmacokinetic Assessment of a 5 Day Infusion of Gallium Nitrate (IV Ganite®)
Description
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.
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
Title
Number of Serious Adverse Events
Description
Safety as measured by serous adverse events
Time Frame
56 days from starting dose
Title
Number of Events When Study Drug Infusion Was Stopped Early
Description
Tolerability as measured by adverse events of a 5 day continuous infusion of IV Gallium as assessed by stopping study drug infusion
Time Frame
6 days from starting dose
Secondary Outcome Measure Information:
Title
Change in Spirometry From Baseline to Day 8
Description
Change in spirometry as measured by FEV1 in liters from baseline to day 8
Time Frame
8 days
Title
Change in Lung Function From Baseline to Day 15
Description
Change in FEV1 in liters from baseline to day 15
Time Frame
15 days from starting dose
Title
Change in Spirometry From Baseline to Day 28
Description
Change in lung function as measured by FEV1 in liters from baseline to day 28
Time Frame
28 days from starting dose
Title
Change in Spirometry From Baseline to Day 56
Description
Change in lung function as measured by FEV1 in liters from baseline to day 56
Time Frame
56 days from starting dose
Title
Change in Spirometry as Measured by FVC From Baseline to Day 8
Description
Change from baseline in lung function assessed by FVC in liters after treatment with IV Ga at day 8
Time Frame
8 days from starting dose
Title
Change in P. Aeruginosa Density From Baseline to Day 8
Description
Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 8
Time Frame
8 days from starting dose
Title
Change in Sputum P. Aeruginosa Density From Baseline to Day 15
Description
Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 15
Time Frame
15 days from starting dose
Title
Change in P. Aeruginosa Density From Baseline to Day 56
Description
Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 56
Time Frame
56 days from starting dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christopher H Goss, MD, MSc
Organizational Affiliation
University of Washington
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242-1083
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients
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