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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT01093521
• Collaborator: Cystic Fibrosis Foundation (Other)
• Enrollment: 20
• Locations: 3
• Arms: 2
• Duration (Months): 41
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.2

Study Details

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)

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: 100 mg/m2 dose; Drug: 200 mg/m2 dose	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Pharmacokinetic and Safety Study of IV Gallium Nitrate (Ganite) in Cystic Fibrosis Patients
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Aug 31, 2013

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetic Assessment of a 5 Day Infusion of Gallium Nitrate (IV Ganite®) [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.

2. Number of Serious Adverse Events [56 days from starting dose]

   Safety as measured by serous adverse events

3. Number of Events When Study Drug Infusion Was Stopped Early [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

Secondary Outcome Measures

1. Change in Spirometry From Baseline to Day 8 [8 days]

   Change in spirometry as measured by FEV1 in liters from baseline to day 8

2. Change in Lung Function From Baseline to Day 15 [15 days from starting dose]

   Change in FEV1 in liters from baseline to day 15

3. Change in Spirometry From Baseline to Day 28 [28 days from starting dose]

   Change in lung function as measured by FEV1 in liters from baseline to day 28

4. Change in Spirometry From Baseline to Day 56 [56 days from starting dose]

   Change in lung function as measured by FEV1 in liters from baseline to day 56

5. Change in Spirometry as Measured by FVC From Baseline to Day 8 [8 days from starting dose]

   Change from baseline in lung function assessed by FVC in liters after treatment with IV Ga at day 8

6. Change in P. Aeruginosa Density From Baseline to Day 8 [8 days from starting dose]

   Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 8

7. Change in Sputum P. Aeruginosa Density From Baseline to Day 15 [15 days from starting dose]

   Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 15

8. Change in P. Aeruginosa Density From Baseline to Day 56 [56 days from starting dose]

   Change in sputum microbiology (specifically P. aeruginosa density based on quantitative cultures) from baseline to day 56

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

4. Documented history of > 60 mmol/L chloride concentration in pilocarpine sweat chloride test And/Or

5. Genotype with two identifiable mutations consistent with CF, accompanied by one or more phenotypic features consistent with diagnosis of CF

6. Forced expiratory volume in the first second (FEV1) ≥ 30% of predicted value

7. Able to expectorate sputum

8. Serum liver function tests ≤ 2.5 x upper limit of normal

9. Serum urea nitrogen (BUN) and creatinine ≤ 1.5 x upper limit of normal

10. Serum creatinine ≤ 2.0 mg/dl

11. Hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/mm3, and white blood cells (WBC) ≥ 4,500/mm3 and ≤ 15,000/mm3

12. Ionized calcium ≥ the lower limit of normal

13. Able to understand and sign the informed consent document, communicate with the Investigator, and comply with the requirements of the protocol

14. If female and of childbearing potential, must have a negative pregnancy test on Day 1 prior to receiving study drug

15. 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

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa	Iowa City	Iowa	United States	52242-1083
2	Johns Hopkins University	Baltimore	Maryland	United States	21201
3	University of Washington	Seattle	Washington	United States	98195

Sponsors and Collaborators

• University of Washington
• Cystic Fibrosis Foundation

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Chris Goss, Associate Professor, University of Washington
• ClinicalTrials.gov Identifier: NCT01093521
• Other Study ID Numbers: 35876; US FDA 5R01FD003704
• First Posted: Mar 26, 2010
• Last Update Posted: Jan 29, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Chris Goss, Associate Professor, University of Washington: IV Gallium; Gallium; Ganite; Cystic Fibrosis; Gallium Infusion
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Gallium nitrate

Study Results

Participant Flow

Recruitment Details	Subjects were recruited in the Adult cystic fibrosis clinics at 3 centers (the University of Washington, University of Iowa, John's Hopkins University) from the second quarter 2010 and closed February 1, 2012. The study had two dosing cohorts. Cohort 1 completed enrollment in February, 2011. Cohort 2 completed enrollment on February 1, 2012.
Pre-assignment Detail	We employed no run-in period. No subjects withdrew after randomization.

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Overall Participants	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	32.8 (9.5)
Sex: Female, Male (Count of Participants)
Female	10 50%
Male	10 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	19 95%
More than one race	0 0%
Unknown or Not Reported	1 5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5%
Not Hispanic or Latino	17 85%
Unknown or Not Reported	2 10%
Region of Enrollment (participants) [Number]
United States	20 100%
Forced expiratory volume in one second (FEV1) (in liters) (liters) [Mean (Full Range) ]
Mean (Full Range) [liters]	2.25
Forced vital capacity (FVC)(in liters) (liters) [Mean (Full Range) ]
Mean (Full Range) [liters]	3.60
Mean Pseudomonas aeruginosa quantitative sputum culture (CFU's/gr of sputum) (Million CFU/gr of sputum) [Mean (Full Range) ]
Mean (Full Range) [Million CFU/gr of sputum]	116.7

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Gallium (Ganite®) Infusion	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 200 mg/m2/day
Measure Participants	9	11
Mean (Standard Deviation) [ug*hr/mL]	503 (98)	537 (153)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	20
Mean (Standard Deviation) [liters]	0.13 (0.18)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	20
Mean (Standard Deviation) [liters]	0.13 (0.17)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	20
Mean (Standard Deviation) [liters]	0.10 (0.14)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

all those subjects enrolled after the amendment to add a day 56 (ITT)

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	11
Mean (Standard Deviation) [liters]	0.12 (0.19)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	20
Mean (Standard Deviation) [liters]	0.16 (0.20)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All available specimens

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	19
Mean (Standard Deviation) [colony counts in millions per gm sputum]	21.1 (297.5)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	19
Mean (Standard Deviation) [colony counts in millions per gm sputum]	-5.5 (217.9)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All available specimens

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	5
Mean (Standard Deviation) [colony counts in millions per gm sputum]	-76.0 (58.3)

10. Primary Outcome

Title	Number of Serious Adverse Events
Description	Safety as measured by serous adverse events
Time Frame	56 days from starting dose

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	20
Number [Serious Adverse Events]	0

11. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
Measure Participants	20
Number [Number of times study drug interupted]	0

Adverse Events

Time Frame	56 days
Adverse Event Reporting Description	At study visits, all body systems were assessed for adverse events. Serious adverse events were assessed at all study visits and participants were told to inform their research team of any serious adverse events occurring between study visits.
Arm/Group Title	IV Gallium (Ganite®) Infusion
Arm/Group Description	Five day continuous IV Gallium (Ganite®)infusion IV Gallium Nitrate (Ganite®) infusion: 5 day infusion of gallium nitrate (IV Ganite®) at a doses of 100 mg/m2/day and 200 mg/m2/day and 5 day infusion of gallium nitrate (IV Ganite®) 100 mg/m2/day and 200 mg/m2/day
All Cause Mortality
	IV Gallium (Ganite®) Infusion
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IV Gallium (Ganite®) Infusion
	Affected / at Risk (%)	# Events
Total	0/20 (0%)
Other (Not Including Serious) Adverse Events
	IV Gallium (Ganite®) Infusion
	Affected / at Risk (%)	# Events
Total	18/20 (90%)
Blood and lymphatic system disorders
Lymphadenopathy	1/20 (5%)	1
Congenital, familial and genetic disorders
Cystic fibrosis lung	3/20 (15%)	3
Ear and labyrinth disorders
External ear inflammation	2/20 (10%)	2
Gastrointestinal disorders
Abdominal distension	1/20 (5%)	1
Abdominal pain	2/20 (10%)	2
Gastrointestinal reflux disease	1/20 (5%)	1
Nausea	1/20 (5%)	1
Stomach discomfort	1/20 (5%)	1
vomiting	1/20 (5%)	1
General disorders
fatigue	4/20 (20%)	4
Peripheral edema	1/20 (5%)	1
pyrexia	1/20 (5%)	1
Infections and infestations
urinary tract infection	1/20 (5%)	5
Injury, poisoning and procedural complications
infusion site bruising	3/20 (15%)	3
infusion site hematoma	1/20 (5%)	1
infusion site pain	1/20 (5%)	1
infusion site swelling	1/20 (5%)	1
Investigations
Blood glucose increased	1/20 (5%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/20 (10%)	3
Gout	1/20 (5%)	1
Muscle spasms	1/20 (5%)	1
neck stiffness	1/20 (5%)	1
Pain in extremity	1/20 (5%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Paresthesia	1/20 (5%)	2
Nervous system disorders
Dizziness	1/20 (5%)	1
headache	9/20 (45%)	16
Migraine	1/20 (5%)	1
Renal and urinary disorders
albuminuria	1/20 (5%)	1
Haematuria	2/20 (10%)	2
Pyuria	1/20 (5%)	1
Reproductive system and breast disorders
Pelvic pain	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
cough	4/20 (20%)	4
crackles lung	1/20 (5%)	1
Dyspnoea	2/20 (10%)	2
Haemoptysis	5/20 (25%)	5
Nasal congestion	3/20 (15%)	3
Epistaxis	1/20 (5%)	1
Non-cardiac chest pain	3/20 (15%)	3
Productive cough	3/20 (15%)	3
Rhinitis	2/20 (10%)	2
sinus congestion	3/20 (15%)	4
Sinus disorder	1/20 (5%)	1
Sputum discolored	1/20 (5%)	1
Throat irritation	3/20 (15%)	3
Upper respiratory infection	1/20 (5%)	1
Voice alteration	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Rash	1/20 (5%)	1

Limitations/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.

More Information

Certain Agreements

Principal Investigators are NOT 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.