A Phase 2 IV Gallium Study for Patients With Cystic Fibrosis (IGNITE Study)

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT02354859
• Collaborator: Cystic Fibrosis Foundation (Other)
• Enrollment: 119
• Locations: 23
• Arms: 2
• Actual Duration (Months): 23.1
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy of IV gallium to improve pulmonary function as measured by a 5% or greater relative improvement in forced expiratory volume in one second (FEV1) from baseline to Day 28.

Funding Source - FDA OOPD

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: Gallium nitrate; Drug: Normal Saline	Phase 2

Detailed Description

This is a phase 2, multi-center, randomized, placebo-controlled trial in adults with CF chronically infected with P. aeruginosa. The study will evaluate the safety and clinical efficacy of a five day infusion of IV gallium nitrate (IV gallium). The purpose of this study is to assess the efficacy of IV gallium to improve pulmonary function as measured by a 5% or greater relative improvement in forced expiratory volume in one second (FEV1) from baseline to Day 28.

Study Design

• Study Type: Interventional
• Actual Enrollment: 119 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multi-Center, Randomized, Placebo-Controlled Study of IV Gallium Nitrate in Patients With Cystic Fibrosis (IGNITE Study)
• Actual Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Feb 1, 2018
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 5 day of infusion of gallium nitrate Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days.	Drug: Gallium nitrate; Study subjects will receive an infusion of either placebo or gallium nitrate.; Other Names: Ga, GaN3O9
Placebo Comparator: 5 day of infusion of normal saline Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga	Drug: Normal Saline; Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.; Other Names: Sodium Chloride, NS

Outcome Measures

Primary Outcome Measures

1. Number of Participants With 5% or Greater Relative Change in FEV1 (Liters) From Baseline to Day 28 [Baseline to Day 28]

   Difference between treatment groups in the proportion of subjects with 5% or greater relative change in FEV1 (liters) from baseline to Day 28.

Secondary Outcome Measures

1. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 to Day 56]

   Incidence is defined as the number and percentage of participants with at least one event over the 56 day follow-up period.

2. Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Day 1 to Day 56]

   Rate is defined as the number of events per participant follow-up week.

3. Relative Change in FEV1 (Liters) From Baseline to Day 56 [Day 1 to Day 56]

   Difference between treatment groups in the relative change in FEV1 (liters) from Baseline to Day 56

4. Absolute Change in P. Aeruginosa Sputum Density (log10 (CFU)) From Baseline to Day 56 [Day 1 to Day 56]

   Difference between treatment groups in the absolute change in P. aeruginosa sputum density (log10 (CFU)) from Baseline to Day 56 based on quantitative cultures.

5. Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), From Baseline to Day 56 [Day 1 to Day 56]

   Difference between treatment groups in the absolute change in respiratory symptoms, as measured by the the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), from Baseline to Day 56. The Cystic Fibrosis Respiratory Symptoms Daily Diary asks a participant to state the extent of their 8 respiratory symptoms : difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Greater than or equal to 18 years of age at Screening

• Documented chronic colonization with P. aeruginosa defined as dentification in two sputum or oropharyngeal cultures within the year prior to Day 1

• Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:

1. sweat chloride ≥ 60 mEq/liter by quantitative pilocarpine iontophoresis test (QPIT)

2. two well-characterized mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene

3. Abnormal nasal potential difference (NPD; change in NPD in response to a low chloride solution and isoproteronol of less than -5 mV)

• FEV1 ≥ 25 % of predicted value at Screening

• Able to expectorate sputum

• Serum liver function tests ≤ 2.5 x upper limit of normal at Screening

• Serum urea nitrogen (BUN) ≤ 1.5 x upper limit of normal at Screening

• Serum creatinine ≤ 2.0 mg/dl and ≤ 1.5 x upper limit of normal at Screening

• Hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/mm3, and white blood cells (WBC)

≥ 4,500/mm3 at Screening

• Ionized calcium ≥ lower limit of normal at Screening

• Written informed consent obtained from subject or subject's legal representative

• Able to 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 for the duration of the study through Visit 5, as determined by the investigator

• If male and able to father a child, is willing to use adequate contraception for the duration of the study through Visit 5, as determined by the investigator

• Clinically stable with no significant changes in health status within 14 days prior to Day 1

Exclusion criteria:

• Use of inhaled antibiotics within seven days prior to Day 1

• Unable or unwilling to withhold use of chronic inhaled antibiotics through Day 28

• Use of intravenous, inhaled, or oral antibiotics for an acute indication within 14 days prior to Day 1

• Use of bisphosphonates within seven days prior to Day 1

• History of osteoporosis (defined as the most recent dexa scan with a T-score ≤ -2.5 with the dexa scan performed within the five years prior to Screening)

• Lactating female

• Known sensitivity to gallium

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AL Adult Birmingham / The Children's Hospital Atlanta	Birmingham	Alabama	United States	35233
2	UC San Diego Medical Center	La Jolla	California	United States	92037
3	Denver Adult / National Jewish Health	Denver	Colorado	United States	80206
4	Shands Hospital	Gainesville	Florida	United States	32610
5	Jackson Memorial Hospital; University of Miami Hospital; University of Miami Hospital and Clinics	Miami	Florida	United States	33136
6	Atlanta Emory Adult / Emory University Hospital	Atlanta	Georgia	United States	30322
7	Chicago Northwestern Adult / Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
8	Iowa City University of Iowa Adult / University of Iowa Hospitals & Clinics	Iowa City	Iowa	United States	52242
9	Lexington, KY Adult / University of Kentucky Chandler Medical Center	Lexington	Kentucky	United States	40506-9983
10	Portland, ME Adult	Portland	Maine	United States	04102
11	Baltimore Hopkins Adult / John Hopkins Hospital	Baltimore	Maryland	United States	21205
12	Boston CHB Adult / Boston Children's Hospital (BCH)	Boston	Massachusetts	United States	02115
13	Minneapolis CC and Adult / University of Minnesota Medical Center, Fairview	Minneapolis	Minnesota	United States	55455
14	Omaha Adult / The Nebraska Medical Center	Omaha	Nebraska	United States	68198-5300
15	Lebanon, NH Dartmouth-Hitchcock CC and Adult / Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
16	Cleveland CC and Peds, Hospital of Cleveland	Cleveland	Ohio	United States	44106
17	Columbus CC and Peds / Nationwide Children's Hospital	Columbus	Ohio	United States	43205
18	Toledo, OH CC and Peds / The Toledo Hospital; Toledo Children's Hospital	Toledo	Ohio	United States	43606
19	Oklahoma City Adult / Presbyterian Hospital at OU Medical Center	Oklahoma City	Oklahoma	United States	73104
20	Pittsburgh Adult, Children's Hospital of Pittsburgh UPMC	Pittsburgh	Pennsylvania	United States	15224
21	SC CC and Adult Charleston / MUSC	Charleston	South Carolina	United States	29425
22	Salt Lake City Adult, Intermountain Cystic Fibrosis Center	Salt Lake City	Utah	United States	84132
23	Seattle UW Adult / University of Washington Medical Center	Seattle	Washington	United States	98195

Sponsors and Collaborators

• University of Washington
• Cystic Fibrosis Foundation

Investigators

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

Study Documents (Full-Text)

• Statistical Analysis Plan - Oct 6, 2016
• Study Protocol - Aug 28, 2014

More Information

Publications

None provided.

• Responsible Party: Chris Goss, Professor, Medicine/Pulmonary & Critical Care Medicine, University of Washington
• ClinicalTrials.gov Identifier: NCT02354859
• Other Study ID Numbers: STUDY00002609; 2R01FD003704-03A1
• First Posted: Feb 3, 2015
• Last Update Posted: Mar 21, 2019
• Last Verified: Mar 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Chris Goss, Professor, Medicine/Pulmonary & Critical Care Medicine, University of Washington: Cystic Fibrosis; Gallium Nitrate; IV Gallium; Pseudomonas aeruginosa
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Gallium nitrate

Study Results

Participant Flow

Arm/Group Title	Gallium	Placebo
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.	Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
Period Title: Overall Study
STARTED	60	59
COMPLETED	60	57
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Gallium	Placebo	Total
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.	Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.	Total of all reporting groups
Overall Participants	60	59	119
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.7 (10.25)	33.8 (9.62)	32.8 (9.96)
Age, Customized (Count of Participants)
Between 18 and 30 years	30 50%	23 39%	53 44.5%
>= 30 years	30 50%	36 61%	66 55.5%
Sex: Female, Male (Count of Participants)
Female	31 51.7%	24 40.7%	55 46.2%
Male	29 48.3%	35 59.3%	64 53.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 3.3%	1 1.7%	3 2.5%
Not Hispanic or Latino	58 96.7%	58 98.3%	116 97.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	58 96.7%	58 98.3%	116 97.5%
More than one race	1 1.7%	1 1.7%	2 1.7%
Unknown or Not Reported	1 1.7%	0 0%	1 0.8%
Region of Enrollment (participants) [Number]
United States	60 100%	59 100%	119 100%
Cystic Fibrosis (CF) Genotype (Count of Participants)
Delta F508 Homozygous	34 56.7%	38 64.4%	72 60.5%
Delta F508 Heterozygous	21 35%	18 30.5%	39 32.8%
Other	5 8.3%	2 3.4%	7 5.9%
Unidentified	0 0%	0 0%	0 0%
Not Available	0 0%	1 1.7%	1 0.8%
Forced Expiratory Volume in 1 second (FEV1) (liters) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liters]	2.0 (0.95)	2.0 (0.79)	2.0 (0.87)
FEV1 (% Predicted) Distribution (Count of Participants)
< 50%	28 46.7%	29 49.2%	57 47.9%
Between 50 and 70%	15 25%	12 20.3%	27 22.7%
> 70%	17 28.3%	18 30.5%	35 29.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With 5% or Greater Relative Change in FEV1 (Liters) From Baseline to Day 28
Description	Difference between treatment groups in the proportion of subjects with 5% or greater relative change in FEV1 (liters) from baseline to Day 28.
Time Frame	Baseline to Day 28

Outcome Measure Data

Analysis Population Description

Includes only treated participants with FEV1 measurements at Baseline and Day 28.

Arm/Group Title	Gallium	Placebo
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.	Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
Measure Participants	60	56
Count of Participants [Participants]	22 36.7%	17 28.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gallium, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.811
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 95%; -11.2 to 22.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimate is adjusted for baseline FEV1 % predicted strata (<50% of predicted, between 50% and 70% of predicted, and >70% of predicted).

2. Secondary Outcome

Title	Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Incidence is defined as the number and percentage of participants with at least one event over the 56 day follow-up period.
Time Frame	Day 1 to Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gallium	Placebo
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.	Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
Measure Participants	60	59
Incidence of AEs	57 95%	57 96.6%
Incidence of SAEs	11 18.3%	9 15.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gallium, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.807
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions-SAE inicidence
	Estimated Value	3.1
	Confidence Interval	(2-Sided) 95%; -10.6 to 16.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% confidence interval calculated using the Newcombe-Wilson method without continuity correction.

3. Secondary Outcome

Title	Rate of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Rate is defined as the number of events per participant follow-up week.
Time Frame	Day 1 to Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gallium	Placebo
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.	Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
Measure Participants	60	59
Number of AEs per participant week	0.84	1.03
Number of SAEs per participant week	0.02	0.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gallium, Placebo
	Comments	Rate Ratio for Adverse Events calculated using Poisson Regression with an offset for the log of follow-up time in weeks. The total number of follow-up weeks of all participants (not per participant) in the trial was as follows: in the IV Gallium group was 486.86 and in the Placebo group was 473.57.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Poisson Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.71 to 0.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gallium, Placebo
	Comments	Rate Ratio for Serious Adverse Events calculated using Poisson Regression with an offset for the log of follow-up time in weeks. The total number of follow-up weeks in the IV Gallium group was 486.86 and in the Placebo group was 473.57.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.783
	Comments
	Method	Poisson Regression
	Comments
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.39 to 2.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Relative Change in FEV1 (Liters) From Baseline to Day 56
Description	Difference between treatment groups in the relative change in FEV1 (liters) from Baseline to Day 56
Time Frame	Day 1 to Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gallium	Placebo
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.	Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
Measure Participants	60	59
Mean (Standard Error) [percentage change]	1.89 (16.99)	-0.05 (14.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gallium, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.479
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.05
	Confidence Interval	(2-Sided) 95%; -3.66 to 7.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis includes all data for relative change from baseline at Day 6, Day 14, Day 28, and Day 56. Mixed-effects repeated measures model includes terms for the baseline FEV1 (liters), treatment, visit and a visit-by-visit interaction.

5. Secondary Outcome

Title	Absolute Change in P. Aeruginosa Sputum Density (log10 (CFU)) From Baseline to Day 56
Description	Difference between treatment groups in the absolute change in P. aeruginosa sputum density (log10 (CFU)) from Baseline to Day 56 based on quantitative cultures.
Time Frame	Day 1 to Day 56

Outcome Measure Data

Analysis Population Description

Includes only participants with a positive P. aeruginosa (Pa) culture at Baseline.

Arm/Group Title	Gallium	Placebo
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.	Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
Measure Participants	47	45
Mean (Standard Error) [log10 (CFU)]	-1.06 (1.97)	-0.33 (1.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gallium, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.054
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.74
	Confidence Interval	(2-Sided) 95%; -1.49 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis includes all data for relative change from baseline at Day 28 and Day 56. Mixed-effects repeated measures model includes terms for the baseline Pa density (log10 (CFU)), treatment, visit and a visit-by-visit interaction.

6. Secondary Outcome

Title	Absolute Change in Respiratory Symptoms, as Measured by the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), From Baseline to Day 56
Description	Difference between treatment groups in the absolute change in respiratory symptoms, as measured by the the CF Respiratory Symptoms Diary-Chronic Respiratory Infection Symptom Severity Score (CFRSD-CRISS), from Baseline to Day 56. The Cystic Fibrosis Respiratory Symptoms Daily Diary asks a participant to state the extent of their 8 respiratory symptoms : difficulty breathing, feverishness, tiredness, chills or sweats, coughing, coughing up mucus, tightness in the chest and wheezing. Each respiratory symptom is assigned a score from 0-4 based on the response, with zero corresponding to the absence of the symptom and four corresponding to symptom being present 'a great deal' or 'extremely'. A summed score (range from 0-24) is calculated for each participant and converted to a final score with a range of 0 to 100, where the lowest scores indicate improvement of symptoms.
Time Frame	Day 1 to Day 56

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gallium	Placebo
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.	Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
Measure Participants	60	59
Mean (Standard Error) [score on a scale]	3.03 (13.66)	-0.98 (10.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gallium, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.053
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.23
	Confidence Interval	(2-Sided) 95%; -0.06 to 8.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis includes all data for relative change from baseline at Day 6, Day 14, Day 28, and Day 56. Mixed-effects repeated measures model includes terms for the baseline CFRSD-CRISS score, treatment, visit and a visit-by-visit interaction.

Adverse Events

Time Frame	For Serious Adverse Events (SAEs): Informed consent to Day 56. For all Other (Not Including Serious) AEs: Start of study drug to final study visit (Day 56).
Arm/Group Title	Gallium		Placebo
Arm/Group Description	Gallium nitrate will be infused continuously over 5 days at 200 mg/m2/day. Study drug will be administered via a peripheral IV catheter, a peripherally inserted central catheter (PICC) line, midline catheter, or a chronic indwelling vascular access device () using an ambulatory infusion pump infused over 24 hours for 5 sequential days. Gallium nitrate: Study subjects will receive an infusion of either placebo or gallium nitrate.		Placebo with be dispensed as 1,000 milliliters of 0.9% sodium chloride to match the reconstitution volume of the IV Ga Normal Saline: Study subjects will receive an infusion of either placebo (normal saline) or gallium nitrate.
All Cause Mortality
	Gallium		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/59 (0%)
Serious Adverse Events
	Gallium		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/60 (18.3%)		9/59 (15.3%)
Blood and lymphatic system disorders
Haemolytic anaemia	0/60 (0%)	0	1/59 (1.7%)	1
Eye disorders
Visual impairment	0/60 (0%)	0	1/59 (1.7%)	1
Gastrointestinal disorders
Abdominal pain	0/60 (0%)	0	1/59 (1.7%)	1
Distal intestinal obstruction syndrome	1/60 (1.7%)	1	0/59 (0%)	0
Nausea	0/60 (0%)	0	1/59 (1.7%)	1
Vomiting	0/60 (0%)	0	1/59 (1.7%)	1
General disorders
Chest discomfort	3/60 (5%)	3	3/59 (5.1%)	4
Chills	0/60 (0%)	0	1/59 (1.7%)	1
Exercise tolerance decreased	1/60 (1.7%)	1	0/59 (0%)	0
Fatigue	3/60 (5%)	3	3/59 (5.1%)	3
Malaise	0/60 (0%)	0	1/59 (1.7%)	1
Pain	0/60 (0%)	0	1/59 (1.7%)	1
Pyrexia	1/60 (1.7%)	1	4/59 (6.8%)	5
Infections and infestations
Upper respiratory tract infection	0/60 (0%)	0	1/59 (1.7%)	1
Investigations
Blood creatinine increased	0/60 (0%)	0	1/59 (1.7%)	1
Forced expiratory volume decreased	1/60 (1.7%)	1	0/59 (0%)	0
Pulmonary function test decreased	2/60 (3.3%)	2	0/59 (0%)	0
Weight decreased	1/60 (1.7%)	1	2/59 (3.4%)	2
Metabolism and nutrition disorders
Decreased appetite	0/60 (0%)	0	2/59 (3.4%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	1/60 (1.7%)	1	0/59 (0%)	0
Myalgia	1/60 (1.7%)	1	1/59 (1.7%)	1
Nervous system disorders
Migraine with aura	0/60 (0%)	0	1/59 (1.7%)	1
Seizure	1/60 (1.7%)	1	0/59 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	7/60 (11.7%)	7	7/59 (11.9%)	8
Dyspnoea	5/60 (8.3%)	5	8/59 (13.6%)	11
Dyspnoea exertional	1/60 (1.7%)	1	0/59 (0%)	0
Haemoptysis	0/60 (0%)	0	1/59 (1.7%)	3
Hypoxia	0/60 (0%)	0	1/59 (1.7%)	1
Increased viscosity of bronchial secretion	0/60 (0%)	0	1/59 (1.7%)	1
Nasal congestion	0/60 (0%)	0	1/59 (1.7%)	1
Pleuritic pain	0/60 (0%)	0	1/59 (1.7%)	1
Pulmonary congestion	0/60 (0%)	0	1/59 (1.7%)	1
Rales	0/60 (0%)	0	1/59 (1.7%)	1
Sputum increased	3/60 (5%)	3	5/59 (8.5%)	5
Wheezing	1/60 (1.7%)	1	0/59 (0%)	0
Skin and subcutaneous tissue disorders
Night sweats	0/60 (0%)	0	2/59 (3.4%)	2
Other (Not Including Serious) Adverse Events
	Gallium		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/60 (88.3%)		55/59 (93.2%)
Gastrointestinal disorders
Abdominal pain	6/60 (10%)	7	5/59 (8.5%)	5
Abdominal pain upper	1/60 (1.7%)	1	3/59 (5.1%)	3
Constipation	2/60 (3.3%)	2	3/59 (5.1%)	3
Diarrhoea	4/60 (6.7%)	5	7/59 (11.9%)	7
Nausea	9/60 (15%)	13	11/59 (18.6%)	13
Vomiting	4/60 (6.7%)	6	6/59 (10.2%)	6
General disorders
Asthenia	6/60 (10%)	6	2/59 (3.4%)	2
Chest discomfort	12/60 (20%)	12	13/59 (22%)	15
Chest pain	5/60 (8.3%)	6	4/59 (6.8%)	5
Chills	0/60 (0%)	0	4/59 (6.8%)	4
Fatigue	19/60 (31.7%)	20	15/59 (25.4%)	16
Pyrexia	7/60 (11.7%)	7	14/59 (23.7%)	16
Injury, poisoning and procedural complications
Contusion	2/60 (3.3%)	2	3/59 (5.1%)	3
Investigations
Pulmonary function test decreased	3/60 (5%)	3	3/59 (5.1%)	3
Weight decreased	4/60 (6.7%)	5	4/59 (6.8%)	4
Metabolism and nutrition disorders
Decreased appetite	8/60 (13.3%)	9	4/59 (6.8%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	1/60 (1.7%)	1	3/59 (5.1%)	4
Muscle spasms	4/60 (6.7%)	4	0/59 (0%)	0
Myalgia	6/60 (10%)	6	5/59 (8.5%)	5
Pain in extremity	4/60 (6.7%)	4	1/59 (1.7%)	1
Nervous system disorders
Headache	17/60 (28.3%)	20	23/59 (39%)	28
Sinus headache	2/60 (3.3%)	2	3/59 (5.1%)	5
Psychiatric disorders
Insomnia	0/60 (0%)	0	3/59 (5.1%)	3
Respiratory, thoracic and mediastinal disorders
Cough	29/60 (48.3%)	33	27/59 (45.8%)	34
Dyspnoea	8/60 (13.3%)	9	14/59 (23.7%)	17
Haemoptysis	7/60 (11.7%)	11	10/59 (16.9%)	11
Nasal congestion	5/60 (8.3%)	6	6/59 (10.2%)	6
Oropharyngeal pain	8/60 (13.3%)	10	7/59 (11.9%)	9
Paranasal sinus hypersecretion	4/60 (6.7%)	4	1/59 (1.7%)	1
Pulmonary congestion	4/60 (6.7%)	5	6/59 (10.2%)	6
Rales	1/60 (1.7%)	1	6/59 (10.2%)	8
Rhinorrhoea	4/60 (6.7%)	4	6/59 (10.2%)	12
Sinus congestion	9/60 (15%)	9	2/59 (3.4%)	2
Sputum increased	19/60 (31.7%)	21	24/59 (40.7%)	30
Upper-airway cough syndrome	1/60 (1.7%)	1	3/59 (5.1%)	3
Wheezing	5/60 (8.3%)	5	8/59 (13.6%)	11
Skin and subcutaneous tissue disorders
Night sweats	1/60 (1.7%)	1	5/59 (8.5%)	5
Rash	4/60 (6.7%)	4	1/59 (1.7%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.