FAST GFR: Pilot Study to Evaluate the Safety of the FAST GFR Test in Patients.

• Sponsor: FAST BioMedical (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01978314
• Collaborator: National Institutes of Health (NIH) (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 33
• Location: 1
• Arms: 5
• Duration (Months): 12
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

This is a single site study designed to evaluate the FAST mGFR Test™ in healthy adult volunteers, patients with varying degrees of chronic kidney disease (CKD), and patients with acute kidney injury (AKI).

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease; Acute Kidney Injury	Device: 75 mg / 6 mL VFI™	N/A

Detailed Description

A rapid and accurate measurement of glomerular filtration rate (GFR) is important in acute kidney injury (AKI) and chronic kidney disease (CKD) for assessment of impairment, diagnosis, and prompt treatment. FAST BioMedical is an emerging technology company whose mission is to quantify clinically meaning ful physiological parameters that have been difficult or impossible to measure. GFR is the most clinically relevant metric for understanding renal function, as it is the rate by which the kidney is able to filter waste products in the bloodstream. The FAST mGFR is for direct measurement of GFR that relies on reading the ratio of fluorescent markers attached to different size dextran molecules introduced into the bloodstream. The test is intended as an adjunct to current methods utilized to assess kidney function.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This pilot study was a prospective, open-label, single site study designed to evaluate the safety of the FAST mGFR Test™ in healthy adult volunteers, patients with varying degrees of renal impairment and hemodynamically stable AKI.This pilot study was a prospective, open-label, single site study designed to evaluate the safety of the FAST mGFR Test™ in healthy adult volunteers, patients with varying degrees of renal impairment and hemodynamically stable AKI.
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Single-Center Prospective Study Evaluating the FAST Measured Glomerular Filtration Rate (mGFR) Test™ in Adults With Preserved Kidney Function and Impaired Kidney Function With Comparison to Iohexol Clearance Methods
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Experimental: Cohort 2 eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Experimental: Cohort 3 eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Experimental: Cohort 4 a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Experimental: Cohort 5 eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	Device: 75 mg / 6 mL VFI™; Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [Baseline through day 22]

   An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product or investigational medical device.

2. Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [Baseline through day 22]

   An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product or investigational medical device.

Secondary Outcome Measures

1. Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   Cmax = maximum observed concentration occurring at Tmax

2. Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   Tmax = time of maximum observed concentration

3. AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   AUClast = area under the concentration-time curve (time 0 to last sample with a quantifiable measurable concentration)

4. AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   AUCall = area under the concentration-time curve (time 0 to last scheduled sample)

5. AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   AUCinf = area under the concentration-time curve (time 0 extrapolated to infinity based on the last observed concentration)

6. T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   T1/2 = terminal half-life = ln(2)/λz

7. Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   Vz = volume of distribution based upon terminal phase

8. Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   Vss = volume of distribution at steady state

9. CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

   CL = total body clearance

10. Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

    Cmax/Dose = maximum observed concentration occurring at Tmax/Dose

11. AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function [PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.]

    AUCinf/Dose = area under the concentration-time curve (time 0 extrapolated to infinity based on the last observed concentration)/Dose

12. To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. [Baseline through Day 22]

    This analysis will compare estimates of kidney function derived from the results of FAST VFI™ to those derived through conventional Iohexol clearance methods.

13. To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. [Baseline through day 22]

    This analysis will compare estimates of plasma volume derived by FAST's plasma volume method with that derived using the conventional Nadler's Formula for plasma volume.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria for Groups 1-3:

• Female subjects: women must have a negative urine pregnancy test at screening and before dosing on Visit 2 and be either confirmed by the Investigator to be infertile or using a reliable method of contraception Male subjects: reproductively active men must agree to either practice abstinence or utilize adequate contraception.

• Ages 19 to 75

• Subject's screening must fall into one of the available categories of estimated glomerular filtration rate (eGFR) renal function: ≥ 60 mL/min for stage normal function; 30-59 mL/min for stage 3, moderate CKD; 15-29 mL/min for stage 4, severe CKD,

• Patients must not be on inotropes or vasopressors, and must be absent of significant hemodynamic instabilities.

• Patients must have ceased use of the following:

• nonsteroidal anti-inflammatory drugs - 6 days prior,

• herbal supplements - 6 days prior to testing and

• cimetidine and trimethoprim - 14 days prior to testing.

• Ability to comply with study conditions

Inclusion Criteria for Group 4:

• Female subjects; women must have a negative urine pregnancy test at screening and before dosing on Visit 2 and be either confirmed by the Investigator to be infertile or using a reliable method of contraception.

Male subjects: reproductively active men must agree to either practice abstinence or utilize adequate contraception.

• Ages 19 to 75

• For cohort 4: patients diagnosed with [either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI]

• Patients must not be on inotropes or vasopressors, and must be absent of significant hemodynamic instabilities.

• Patients must be without evidence of clinically significant liver dysfunction

• Ability to comply with study conditions

Exclusion Criteria for Groups 1-3:

• Positive history of any clinically significant allergic or negative reactions, side effects, or anaphylaxis to sulfa, iodine, dyes, shellfish, isotopes or dextran molecules

• Previous history of nephrectomy or kidney transplant

• A body weight below 40kg

• A body mass index <17 or >40

• Subjects using Coumadin (Warfarin) who have an INR >4 at Screening or pre-dose on Visit 2

• Past history of liver disease or screening Liver Function tests which exceed 1.5 times the upper limit of normal or an albumin of < 2mg/dl.

• Clinically significant illness within 4 weeks or a clinically significant infection within 4 weeks of screening

• Received blood, donated blood, have clinically significant on-going bleeding, changing haemoglobin, or experienced significant blood loss within 2 weeks of dosing

• Subjects with significant abnormal findings upon physical examination, vital signs, ECG, or clinical laboratory results at Screening

• Subjects with a supine blood pressure after resting for at least 5 minutes outside the 90-145 (systolic) or mmHg or 50-95 mmHg (diastolic) range

• Subjects with a supine (ECG) heart rate outside 45-105 beats/min after resting for at least 5 minutes.

• Subjects with a known or suspected history of drug or alcohol misuse within 6 months prior to screening, subjects who have consumed alcohol within 48 hours of dosing, or subjects who the Investigator believes to be unfit to participate in the study due to abuse of illegal or controlled substances.

• Subjects who had a positive result for Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb) screen.

• Subjects who have been diagnosed with acquired immune deficiency syndrome (AIDS), or test positive for human immunodeficiency virus (HIV).

• Subjects who participated in another clinical trial less than 1 month prior to dosing, or who are currently enrolled in another clinical trial.

• Subjects who have any condition that:

• Would make him/her, in the opinion of the Investigator, unsuitable for the study

• Whose condition is likely to deteriorate

• Who, in the opinion of the Investigator, is not likely to complete the study for any reason

Exclusion Criteria for Group 4:

• Positive history of any clinically significant allergic or negative reactions, side effects, or anaphylaxis to sulfa, iodine, dyes, shellfish, isotopes or dextran molecules

• Previous history of nephrectomy or kidney transplant

• A body weight below 40kg

• A body mass index <17 or >40

• Current use of prescribed anticoagulants

• Past history of liver disease or screening Liver Function tests which exceed 1.5 times the upper limit of normal or an albumin of < 2mg/dl.

• Received blood, donated blood, have clinically significant on-going bleeding, changing haemoglobin, or experienced significant blood loss within 2 weeks of dosing

• Subjects with a supine blood pressure after resting for at least 5 minutes outside the 90-145 (systolic) or mmHg or 50-95 mmHg (diastolic) range

• Subjects with a supine (ECG) heart rate outside 45-105 beats/min after resting for at least 5 minutes.

• Subjects with a known or suspected history of drug or alcohol abuse within 6 months prior to admission, who have a positive drug test or alcohol test, or who have consumed alcohol within 24 of testing

• Subjects who had a positive result for Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCVAb) screen.

• Subjects who have been diagnosed with acquired immune deficiency syndrome (AIDS), or test positive for human immunodeficiency virus (HIV).

• Subjects who participated in another clinical trial less than 1 month prior to dosing, or who are currently enrolled in another clinical trial.

• Subjects who have any condition that:

• Would make him/her, in the opinion of the Investigator, unsuitable for the study

• Whose condition is likely to deteriorate

• Who, in the opinion of the Investigator, is not likely to complete the study for any reason

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama Birmingham, Division of Nephrology	Birmingham	Alabama	United States	35294-0007

Sponsors and Collaborators

• FAST BioMedical
• National Institutes of Health (NIH)
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Dana V Rizk, M.D, University of Alabama Birmingham, 205-934-9509, [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Publications

• Wang E, Meier DJ, Sandoval RM, Von Hendy-Willson VE, Pressler BM, Bunch RM, Alloosh M, Sturek MS, Schwartz GJ, Molitoris BA. A portable fiberoptic ratiometric fluorescence analyzer provides rapid point-of-care determination of glomerular filtration rate in large animals. Kidney Int. 2012 Jan;81(1):112-7. doi: 10.1038/ki.2011.294. Epub 2011 Aug 31.

• Responsible Party: FAST BioMedical
• ClinicalTrials.gov Identifier: NCT01978314
• Other Study ID Numbers: FAST mGFR -002; 1R44DK093274-01
• First Posted: Nov 7, 2013
• Last Update Posted: Dec 12, 2017
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by FAST BioMedical: Chronic Kidney Disease; Acute Kidney Injury; AKI; CKD; Plasma Volume; GFR; Glomerular Filtration Rate; Blood volume; mGFR; measured GFR; kidney biomarker; renal disease; renal biomarker; Renal function; kidney function; organ function; kidney monitor; kidney device
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Acute Kidney Injury

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function	eGFR renal function 30-59 mL/min for stage 3, moderate CKD	eGFR renal function 15-29 mL/min for stage 4, severe CKD	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI	eGFR renal function ≥60 mL/min for normal function
Period Title: Overall Study
STARTED	8	8	8	1	8
COMPLETED	8	8	8	1	8
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5	Total
Arm/Group Description	Estimated GFR (mL/min) ≥60 mL/min/1.73m2 BSA	Estimated GFR (mL/min) 30-59 mL/min/1.73m2 BSA	Estimated GFR (mL/min) 15-29 mL/min/1.73m2 BSA	Estimated GFR (mL/min) sCr: ≥2-fold increase or eGFR: >50% decrease compared to baseline	Estimated GFR (mL/min) ≥60 mL/min/1.73m2 BSA	Total of all reporting groups
Overall Participants	8	8	8	1	8	33
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	8 100%	8 100%	8 100%	1 100%	8 100%	33 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.9 (5.19)	56.6 (7.03)	55.6 (17.74)	63.0 (0)	31.8 (14.10)	46.98 (7.78)
Sex: Female, Male (Count of Participants)
Female	3 37.5%	2 25%	2 25%	1 100%	0 0%	8 24.2%
Male	5 62.5%	6 75%	6 75%	0 0%	8 100%	25 75.8%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	8 100%	1 100%	8 100%	33 100%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product or investigational medical device.
Time Frame	Baseline through day 22

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function	eGFR renal function 30-59 mL/min for stage 3, moderate CKD	eGFR renal function 15-29 mL/min for stage 4, severe CKD	sCr: ≥2-fold increase or eGFR: >50% decrease compared to baseline	eGFR renal function ≥60 mL/min for normal function
Measure Participants	8	8	8	1	8
Number [participants]	3 37.5%	4 50%	6 75%	1 100%	5 62.5%

2. Primary Outcome

Title	Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product or investigational medical device.
Time Frame	Baseline through day 22

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function	eGFR renal function 30-59 mL/min for stage 3, moderate CKD	eGFR renal function 15-29 mL/min for stage 4, severe CKD	sCr: ≥2-fold increase or eGFR: >50% decrease compared to baseline	eGFR renal function ≥60 mL/min for normal function
Measure Participants	8	8	8	1	8
Number of treatment-emergent adverse events	5	6	9	3	14
Number of serious treatment-emergent adverse event	0	0	0	0	0

3. Secondary Outcome

Title	Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	Cmax = maximum observed concentration occurring at Tmax
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	8949 (1350)	9725 (1847)	9336 (1553)
FD003	9569 (1809)	10906 (2307)	12663 (2680)

4. Secondary Outcome

Title	Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	Tmax = time of maximum observed concentration
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	0.281 (0.0884)	0.273 (0.0947)	0.25 (0)
FD003	4.33 (8.16)	0.335 (0.27)	2.64 (3.16)

5. Secondary Outcome

Title	AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	AUClast = area under the concentration-time curve (time 0 to last sample with a quantifiable measurable concentration)
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	37594 (12938)	74317 (27069)	18681 (2066)
FD003	1701850 (276886)	1642731 (443350)	1710348 (355518)

6. Secondary Outcome

Title	AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	AUCall = area under the concentration-time curve (time 0 to last scheduled sample)
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	42462 (12128)	80058 (25030)	19924 (2441)
FD003	1701850 (276886)	1642731 (443350)	1710348 (355518)

7. Secondary Outcome

Title	AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	AUCinf = area under the concentration-time curve (time 0 extrapolated to infinity based on the last observed concentration)
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	38844 (12960)	76554 (26430)	19127 (2107)
FD003	1821296 (302728)	1756948 (503557)	1755162 (366071)

8. Secondary Outcome

Title	T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	T1/2 = terminal half-life = ln(2)/λz
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	9.48 (4.28)	18.3 (12.6)	5.64 (1.23)
FD003	123 (38.9)	125 (32.8)	90.9 (10.4)

9. Secondary Outcome

Title	Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	Vz = volume of distribution based upon terminal phase
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	8343 (1733)	7907 (2613)	11451 (3430)
FD003	1177 (293)	1384 (644)	1018 (208)

10. Secondary Outcome

Title	Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	Vss = volume of distribution at steady state
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	5430 (781)	5464 (1425)	6599 (4289)
FD003	1039 (299)	1132 (274)	937 (181)

11. Secondary Outcome

Title	CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	CL = total body clearance
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	677 (190)	143 (39.5)	1404 (242)
FD003	6.82 (1.26)	7.65 (2.67)	7.74 (1.14)

12. Secondary Outcome

Title	Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	Cmax/Dose = maximum observed concentration occurring at Tmax/Dose
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	369 (43.1)	73.8 (18.7)	354 (55)
FD003	787 (125)	877 (135)	956 (197)

13. Secondary Outcome

Title	AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
Description	AUCinf/Dose = area under the concentration-time curve (time 0 extrapolated to infinity based on the last observed concentration)/Dose
Time Frame	PK parameters were evaluated using samples collected pre and post dose at day 2, as well as post dose on days 4, 8, 15, 22.

Outcome Measure Data

Analysis Population Description

Intent-to-treat subject population analyzed. PK was not evaluated in Cohort 1 due to a contamination problem caused by the sample collection catheter used in this cohort. In addition, PK data was not collected for the single subject dosed in Group 4.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol
Measure Participants	0	8	8	0	8
FD001	1641 (590)	1071 (34.6)	731 (129)
FD003	150220 (22006)	141337 (35933)	131599 (19656)

14. Secondary Outcome

Title	To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods.
Description	This analysis will compare estimates of kidney function derived from the results of FAST VFI™ to those derived through conventional Iohexol clearance methods.
Time Frame	Baseline through Day 22

Outcome Measure Data

Analysis Population Description

The subject in Cohort 4 did not receive Iohexol. One subject in Cohort 5 withdrew from the study before receiving Iohexol. Samples were missing for 1 subject in each of Cohorts 1 and 3.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function	eGFR renal function 30-59 mL/min for stage 3, moderate CKD	eGFR renal function 15-29 mL/min for stage 4, severe CKD	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI	eGFR renal function ≥60 mL/min for normal function
Measure Participants	8	8	8	1	8
VFI mGFR	83.20 (16.967)	42.89 (5.810)	30.17 (5.174)	70.86 (0)	65.17 (10.065)
Iohexol GFR	119.25 (9.898)	57.52 (15.816)	31.76 (8.340)	110.52 (12.675)

15. Secondary Outcome

Title	To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume.
Description	This analysis will compare estimates of plasma volume derived by FAST's plasma volume method with that derived using the conventional Nadler's Formula for plasma volume.
Time Frame	Baseline through day 22

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol 75 mg / 6 mL VFI™: Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.	eGFR renal function 30-59 mL/min for stage 3, moderate CKD 75 mg / 6mL VFI™ and 5mL of Iohexol 75 mg / 6 mL VFI™: Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.	eGFR renal function 15-29 mL/min for stage 4, severe CKD 75 mg / 6mL VFI™ and 5mL of Iohexol 75 mg / 6 mL VFI™: Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.	a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI 75 mg / 6mL VFI™ and 5mL of Iohexol 75 mg / 6 mL VFI™: Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.	eGFR renal function ≥60 mL/min for normal function 75 mg / 6mL VFI™ and 5mL of Iohexol 75 mg / 6 mL VFI™: Visible fluorescent injectate, a mixture of two different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.
Measure Participants	8	8	8	1	8
FAST Plasma Volume	3251.088 (452.6180)	2926.941 (568.1260)	2816.244 (533.7910)	6046.770 (0)	2415.950 (569.1105)
Nadler's Formula Plasma Volume	2859.671 (313.2253)	3103.431 (443.1221)	3150.045 (393.3610)	5297.820 (0)	2805.234 (412.2505)

Adverse Events

Time Frame	Baseline through day 22.
Arm/Group Title	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
Arm/Group Description	eGFR renal function ≥60 mL/min for normal function		eGFR renal function 30-59 mL/min for stage 3, moderate CKD		eGFR renal function 15-29 mL/min for stage 4, severe CKD		a diagnosis of either RIFLE stage I or Acute Kidney Injury Network (AKIN) stage 2 AKI		eGFR renal function ≥60 mL/min for normal function
All Cause Mortality
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		0/8 (0%)
Serious Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		0/8 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4		Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)		4/8 (50%)		6/8 (75%)		1/1 (100%)		5/8 (62.5%)
Cardiac disorders
Sinus bradycardia	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Eye disorders
Conjunctival Hyperaemia	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Conjunctival Oedema	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Conjunctivitis	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Miosis	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/1 (100%)		0/8 (0%)
Vision Blurred	2/8 (25%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		0/8 (0%)
Gastrointestinal disorders
Abdominal Pain	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/1 (100%)		0/8 (0%)
Diarrhoea	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Nausea	0/8 (0%)		1/8 (12.5%)		1/8 (12.5%)		0/1 (0%)		2/8 (25%)
Vomiting	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/1 (0%)		2/8 (25%)
General disorders
Oedema	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/1 (0%)		0/8 (0%)
Oedema Peripheral	0/8 (0%)		0/8 (0%)		2/8 (25%)		0/1 (0%)		0/8 (0%)
Pain	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/1 (0%)		0/8 (0%)
Infections and infestations
Tinea Versicolour	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Urinary Tract Infection	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Investigations
Aspartate Aminotransferase Increased	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Blood Creatine Phosphokinase Increased	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Blood Creatinine Increased	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/1 (0%)		0/8 (0%)
Blood Potassium Increased	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/1 (0%)		0/8 (0%)
Cardiac Murmur	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/1 (0%)		0/8 (0%)
Liver Palpable Subcostal	0/8 (0%)		0/8 (0%)		0/8 (0%)		1/1 (100%)		0/8 (0%)
Metabolism and nutrition disorders
Fluid Overload	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/1 (0%)		0/8 (0%)
Nervous system disorders
Migraine	1/8 (12.5%)		0/8 (0%)		1/8 (12.5%)		0/1 (0%)		0/8 (0%)
Psychiatric disorders
Depression	0/8 (0%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		0/8 (0%)
Skin and subcutaneous tissue disorders
Petechiae	0/8 (0%)		0/8 (0%)		1/8 (12.5%)		0/1 (0%)		0/8 (0%)
Pruritis	0/8 (0%)		1/8 (12.5%)		0/8 (0%)		0/1 (0%)		0/8 (0%)
Vascular disorders
Haematoma	1/8 (12.5%)		0/8 (0%)		0/8 (0%)		0/1 (0%)		0/8 (0%)

Limitations/Caveats

Too restrictive entry criteria for enrollment into the AKI cohort and the expiry of the clinical VFI led to a decision, in consultation with FDA, to stop the study prematurely.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.