Acute Kidney Injury, Chronic Kidney Disease
Conditions
Keywords
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
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).
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.
Interventions
DEVICE75 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.
Sponsors
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
FAST BioMedical
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
19 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
| 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) |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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. |
| 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. |
| 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 |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Estimated GFR (mL/min)
≥60 mL/min/1.73m2 BSA | 8 |
| Cohort 2 Estimated GFR (mL/min) 30-59 mL/min/1.73m2 BSA | 8 |
| Cohort 3 Estimated GFR (mL/min) 15-29 mL/min/1.73m2 BSA | 8 |
| Cohort 4 Estimated GFR (mL/min) sCr: ≥2-fold increase or eGFR: \>50% decrease compared to baseline | 1 |
| Cohort 5 Estimated GFR (mL/min)
≥60 mL/min/1.73m2 BSA | 8 |
| Total | 33 |
Baseline characteristics
| Characteristic | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 1 | Cohort 5 | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 1 Participants | 8 Participants | 8 Participants | 33 Participants |
| Age, Continuous | 56.6 years STANDARD_DEVIATION 7.03 | 55.6 years STANDARD_DEVIATION 17.74 | 63.0 years STANDARD_DEVIATION 0 | 27.9 years STANDARD_DEVIATION 5.19 | 31.8 years STANDARD_DEVIATION 14.1 | 46.98 years STANDARD_DEVIATION 7.78 |
| Region of Enrollment United States | 8 participants | 8 participants | 1 participants | 8 participants | 8 participants | 33 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 0 Participants | 5 Participants | 8 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 1 | 0 / 8 |
| other Total, other adverse events | 3 / 8 | 4 / 8 | 6 / 8 | 1 / 1 | 5 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 1 | 0 / 8 |
Outcome results
Primary
Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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
Population: Intent-to-treat subject population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of treatment-emergent adverse events | 5 adverse events |
| Cohort 1 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of serious treatment-emergent adverse event | 0 adverse events |
| Cohort 2 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of treatment-emergent adverse events | 6 adverse events |
| Cohort 2 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of serious treatment-emergent adverse event | 0 adverse events |
| Cohort 3 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of treatment-emergent adverse events | 9 adverse events |
| Cohort 3 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of serious treatment-emergent adverse event | 0 adverse events |
| Cohort 4 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of serious treatment-emergent adverse event | 0 adverse events |
| Cohort 4 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of treatment-emergent adverse events | 3 adverse events |
| Cohort 5 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of treatment-emergent adverse events | 14 adverse events |
| Cohort 5 | Number of Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | Number of serious treatment-emergent adverse event | 0 adverse events |
Primary
Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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
Population: Intent-to-treat subject population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | 3 participants |
| Cohort 2 | Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | 4 participants |
| Cohort 3 | Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | 6 participants |
| Cohort 4 | Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | 1 participants |
| Cohort 5 | Number of Subjects With Adverse Events Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | 5 participants |
Secondary
AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 42462 ng∙hr/mL | Standard Deviation 12128 |
| Cohort 2 | AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1701850 ng∙hr/mL | Standard Deviation 276886 |
| Cohort 3 | AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 80058 ng∙hr/mL | Standard Deviation 25030 |
| Cohort 3 | AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1642731 ng∙hr/mL | Standard Deviation 443350 |
| Cohort 5 | AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 19924 ng∙hr/mL | Standard Deviation 2441 |
| Cohort 5 | AUCall of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1710348 ng∙hr/mL | Standard Deviation 355518 |
Secondary
AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 1641 [(ng∙hr/mL)/(mg/m^2)] | Standard Deviation 590 |
| Cohort 2 | AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 150220 [(ng∙hr/mL)/(mg/m^2)] | Standard Deviation 22006 |
| Cohort 3 | AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 1071 [(ng∙hr/mL)/(mg/m^2)] | Standard Deviation 34.6 |
| Cohort 3 | AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 141337 [(ng∙hr/mL)/(mg/m^2)] | Standard Deviation 35933 |
| Cohort 5 | AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 731 [(ng∙hr/mL)/(mg/m^2)] | Standard Deviation 129 |
| Cohort 5 | AUCinf/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 131599 [(ng∙hr/mL)/(mg/m^2)] | Standard Deviation 19656 |
Secondary
AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 38844 ng∙hr/mL | Standard Deviation 12960 |
| Cohort 2 | AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1821296 ng∙hr/mL | Standard Deviation 302728 |
| Cohort 3 | AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 76554 ng∙hr/mL | Standard Deviation 26430 |
| Cohort 3 | AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1756948 ng∙hr/mL | Standard Deviation 503557 |
| Cohort 5 | AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 19127 ng∙hr/mL | Standard Deviation 2107 |
| Cohort 5 | AUCinf of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1755162 ng∙hr/mL | Standard Deviation 366071 |
Secondary
AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 37594 ng∙hr/mL | Standard Deviation 12938 |
| Cohort 2 | AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1701850 ng∙hr/mL | Standard Deviation 276886 |
| Cohort 3 | AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 74317 ng∙hr/mL | Standard Deviation 27069 |
| Cohort 3 | AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1642731 ng∙hr/mL | Standard Deviation 443350 |
| Cohort 5 | AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 18681 ng∙hr/mL | Standard Deviation 2066 |
| Cohort 5 | AUClast of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1710348 ng∙hr/mL | Standard Deviation 355518 |
Secondary
CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 677 mL/hr/m^2 | Standard Deviation 190 |
| Cohort 2 | CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 6.82 mL/hr/m^2 | Standard Deviation 1.26 |
| Cohort 3 | CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 143 mL/hr/m^2 | Standard Deviation 39.5 |
| Cohort 3 | CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 7.65 mL/hr/m^2 | Standard Deviation 2.67 |
| Cohort 5 | CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 1404 mL/hr/m^2 | Standard Deviation 242 |
| Cohort 5 | CL of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 7.74 mL/hr/m^2 | Standard Deviation 1.14 |
Secondary
Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 369 [(ng/mL)/(mg/m^2)] | Standard Deviation 43.1 |
| Cohort 2 | Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 787 [(ng/mL)/(mg/m^2)] | Standard Deviation 125 |
| Cohort 3 | Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 73.8 [(ng/mL)/(mg/m^2)] | Standard Deviation 18.7 |
| Cohort 3 | Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 877 [(ng/mL)/(mg/m^2)] | Standard Deviation 135 |
| Cohort 5 | Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 354 [(ng/mL)/(mg/m^2)] | Standard Deviation 55 |
| Cohort 5 | Cmax/Dose of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 956 [(ng/mL)/(mg/m^2)] | Standard Deviation 197 |
Secondary
Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 8949 ng/mL | Standard Deviation 1350 |
| Cohort 2 | Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 9569 ng/mL | Standard Deviation 1809 |
| Cohort 3 | Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 9725 ng/mL | Standard Deviation 1847 |
| Cohort 3 | Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 10906 ng/mL | Standard Deviation 2307 |
| Cohort 5 | Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 9336 ng/mL | Standard Deviation 1553 |
| Cohort 5 | Cmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 12663 ng/mL | Standard Deviation 2680 |
Secondary
T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 9.48 hr | Standard Deviation 4.28 |
| Cohort 2 | T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 123 hr | Standard Deviation 38.9 |
| Cohort 3 | T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 18.3 hr | Standard Deviation 12.6 |
| Cohort 3 | T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 125 hr | Standard Deviation 32.8 |
| Cohort 5 | T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 5.64 hr | Standard Deviation 1.23 |
| Cohort 5 | T1/2, z of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 90.9 hr | Standard Deviation 10.4 |
Secondary
Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 0.281 hr | Standard Deviation 0.0884 |
| Cohort 2 | Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 4.33 hr | Standard Deviation 8.16 |
| Cohort 3 | Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 0.335 hr | Standard Deviation 0.27 |
| Cohort 3 | Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 0.273 hr | Standard Deviation 0.0947 |
| Cohort 5 | Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 0.25 hr | Standard Deviation 0 |
| Cohort 5 | Tmax of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 2.64 hr | Standard Deviation 3.16 |
Secondary
To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | VFI mGFR | 83.20 mL/min | Standard Deviation 16.967 |
| Cohort 1 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | Iohexol GFR | 119.25 mL/min | Standard Deviation 9.898 |
| Cohort 2 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | Iohexol GFR | 57.52 mL/min | Standard Deviation 15.816 |
| Cohort 2 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | VFI mGFR | 42.89 mL/min | Standard Deviation 5.81 |
| Cohort 3 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | VFI mGFR | 30.17 mL/min | Standard Deviation 5.174 |
| Cohort 3 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | Iohexol GFR | 31.76 mL/min | Standard Deviation 8.34 |
| Cohort 4 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | VFI mGFR | 70.86 mL/min | Standard Deviation 0 |
| Cohort 5 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | Iohexol GFR | 110.52 mL/min | Standard Deviation 12.675 |
| Cohort 5 | To Compare the Results From the GFR Determined From the FAST VFI™ to GFR Derived From Iohexol Clearance Methods. | VFI mGFR | 65.17 mL/min | Standard Deviation 10.065 |
Secondary
To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume.
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | FAST Plasma Volume | 3251.088 mL | Standard Deviation 452.618 |
| Cohort 1 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | Nadler's Formula Plasma Volume | 2859.671 mL | Standard Deviation 313.2253 |
| Cohort 2 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | FAST Plasma Volume | 2926.941 mL | Standard Deviation 568.126 |
| Cohort 2 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | Nadler's Formula Plasma Volume | 3103.431 mL | Standard Deviation 443.1221 |
| Cohort 3 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | FAST Plasma Volume | 2816.244 mL | Standard Deviation 533.791 |
| Cohort 3 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | Nadler's Formula Plasma Volume | 3150.045 mL | Standard Deviation 393.361 |
| Cohort 4 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | Nadler's Formula Plasma Volume | 5297.820 mL | Standard Deviation 0 |
| Cohort 4 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | FAST Plasma Volume | 6046.770 mL | Standard Deviation 0 |
| Cohort 5 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | FAST Plasma Volume | 2415.950 mL | Standard Deviation 569.1105 |
| Cohort 5 | To Evaluate the Correlation Between FAST's Plasma Volume Method and Standard Clinical Estimates of Plasma Volume. | Nadler's Formula Plasma Volume | 2805.234 mL | Standard Deviation 412.2505 |
Secondary
Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 5430 mL/m^2 | Standard Deviation 781 |
| Cohort 2 | Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1039 mL/m^2 | Standard Deviation 299 |
| Cohort 3 | Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 5464 mL/m^2 | Standard Deviation 1425 |
| Cohort 3 | Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1132 mL/m^2 | Standard Deviation 274 |
| Cohort 5 | Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 6599 mL/m^2 | Standard Deviation 4289 |
| Cohort 5 | Vss of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 937 mL/m^2 | Standard Deviation 181 |
Secondary
Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function
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.
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 2 | Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 8343 mL/m^2 | Standard Deviation 1733 |
| Cohort 2 | Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1177 mL/m^2 | Standard Deviation 293 |
| Cohort 3 | Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 7907 mL/m^2 | Standard Deviation 2613 |
| Cohort 3 | Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1384 mL/m^2 | Standard Deviation 644 |
| Cohort 5 | Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD001 | 11451 mL/m^2 | Standard Deviation 3430 |
| Cohort 5 | Vz of FD001 and FD003 Following Administration of VFI™ in Patients With Varying Degrees of Kidney Function | FD003 | 1018 mL/m^2 | Standard Deviation 208 |