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

NCT01093521 | Completed Phase 1 Results DMC

• 2 other identifiers: 35876US FDA 5R01FD003704
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

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)

Conditions

Cystic Fibrosis

Keywords

IV Gallium; Gallium; Ganite; Cystic Fibrosis; Gallium Infusion

Outcome Measures

Primary Outcomes (3)

• 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.

  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

• Number of Serious Adverse Events

  Safety as measured by serous adverse events

  56 days from starting dose

• 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

  6 days from starting dose

Secondary Outcomes (8)

• 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

Study Arms (2)

100 mg/m2 dose

EXPERIMENTAL

Five day continuous IV Gallium Nitrate (Ganite®) infusion at 100 mg/m2

Drug: 100 mg/m2 dose

200 mg/m2 dose

EXPERIMENTAL

Five day continuous IV Gallium Nitrate (Ganite®) infusion at 200 mg/m2

Drug: 200 mg/m2 dose

Interventions

100 mg/m2 dose DRUG

5 day infusion of gallium nitrate (IV Ganite®) at a dose of 100 mg/m2/day

Also known as: Ganite®, gallium nitrate

100 mg/m2 dose

200 mg/m2 dose DRUG

5 day infusion of gallium nitrate (IV Ganite®) at 200 mg/m2/day

Also known as: Ganite®, gallium nitrate

200 mg/m2 dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (3)

University of Iowa

Iowa City, Iowa, 52242-1083, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21201, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

gallium nitrate

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Limitations and Caveats

The primary limitation of our study was that it was uncontrolled without a blinded placebo. Thus, subjective endpoints could have been biased by either the subjects or the investigators.

Results Point of Contact

• Title: Christopher H. Goss, MD MSc
• Organization: University of Washington

goss@u.washington.edu

206-543-3166

Study Officials

• Christopher H Goss, MD, MSc

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 26, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2012
• Study Completion: August 31, 2013
• Last Updated: November 29, 2022
• Results First Posted: January 12, 2016

Record last verified: 2022-10

Locations

US (3)