The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of FAST PV and mGFR Technology™

NCT03095391 | Completed DMC FDA Device

• 1 other identifier: 36770001
• Study Type: observational
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 2b, prospective, open-label study designed to evaluate the safety, tolerability, PK, and PD of FAST PV and mGFR Technology in healthy subjects and patients with varying degrees of renal impairment.

Conditions

Kidney Diseases; Renal Insufficiency, Chronic; Acute Kidney Injury; Urologic Diseases; Renal Insufficiency

Outcome Measures

Primary Outcomes (13)

• Incidence of serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)

  * Subjects will be monitored for AEs from administration of the first dose of study drug through the end of study visit * Abnormal clinical laboratory tests, physical examination findings, 12-lead electrocardiograms (ECGs), and vital signs including pulse oximetry that (1) are considered clinically significant initially and on confirmation, (2) require a subject to be discontinued from the study, (3) require a subject to receive treatment, or (4) require a change or discontinuation from the study drug (if applicable) will be recorded as AEs

  21 ± 1 days

• Maximum observed plasma concentration (Cmax)

  21 ± 1 days

• Time that Cmax was observed (tmax)

  21 ± 1 days

• Area under the plasma concentration-time curve (AUC) from time 0 to 12 hours (AUC0 12: FD001 only)

  21 ± 1 days

• AUC from time 0 to the time of the last quantifiable concentration (AUClast)

  21 ± 1 days

• AUC from time 0 extrapolated to infinity (AUCinf)

  21 ± 1 days

• Terminal elimination half-life (t½)

  21 ± 1 days

• Terminal elimination rate constant (λz)

  21 ± 1 days

• Total body clearance (CL)

  21 ± 1 days

• Renal clearance (CLr; FD001 only)

  21 ± 1 days

• Volume of distribution during the terminal phase (Vz)

  21 ± 1 days

• Volume of distribution at steady state (Vss)

  21 ± 1 days

• Fraction of dose excreted unchanged in the urine (Ae0-12)

  21 ± 1 days

Secondary Outcomes (6)

• PV as assessed by FAST PV and mGFR Technology

  21 ± 1 days

• PV as assessed by Nadler's formula

  21 ± 1 days

• Changes in PV after fluid challenge

  21 ± 1 days

• Repeatability of GFR measurements over 24 hours

  21 ± 1 days

• mGFR as assessed by FAST VFI and Iohexol clearance methods

  21 ± 1 days

Study Arms (4)

Cohort 1

GFR: ≥ 60 mL/min/1.73 m2 VFI dose: 47 mg/3 mL Number of doses: 1 Comparator: none Comparator dose: none

Device: VFI

Cohort 2

GFR: ≥ 60 mL/min/1.73 m2 VFI dose: 47 mg/3 mL Number of doses: 2 Comparator: Iohexol 5 mL Comparator dose: 1

Device: VFI; Device: Iohexol

Cohort 3

GFR: ≥ 30 and \< 60 mL/min/1.73 m2 VFI dose: 47 mg/3 mL Number of doses: 1 Comparator: Iohexol 5 mL Comparator dose: 1

Device: VFI; Device: Iohexol

Cohort 4

GFR: ≥ 15 and \< 30 mL/min/1.73 m2 VFI dose: 47 mg/3 mL Number of doses: 1 Comparator: Iohexol 5 mL Comparator dose: 1

Device: VFI; Device: Iohexol

Interventions

VFI DEVICE

The IV administered visible fluorescent injectate (VFI)™ agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Iohexol DEVICE

Iohexol is a contrast enhancement agent which, following intravascular injection, is distributed in the extracellular fluid compartment and is excreted unchanged by glomerular filtration.

Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Community sample

You may qualify if:

• All Subjects/Patients:
• Males or females ≥ 18 and ≤ 75 years of age.
• Females must be of non-childbearing potential (eg, postmenopausal \[defined as cessation of regular menstrual periods for at least 1 year confirmed by follicle-stimulating hormone (FSH) test\] or surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation \[documentation required\] or be using a medically acceptable form of birth control \[eg, a barrier method, intrauterine device, or hormonal contraception\]) from screening until 30 days after last dose.
• Males who are sexually active and whose partners are females of childbearing potential must agree to practice abstinence or use condoms from screening through 90 days after administration of the last dose of study drug, and their partners must be willing to use a medically acceptable method of contraception (a barrier method, intrauterine device, or hormonal contraception) from screening through 90 days after administration of the last dose of study drug.
• Males must agree to not donate sperm from screening through 90 days after administration of the last dose of study drug.
• Subjects must be able to communicate effectively with the study personnel.
• Subjects must be informed of the nature and risks of the study and give written informed consent prior to screening.
• Body mass index ≥ 18.0 and ≤ 40.0 kg/m2, and body weight ≥ 40 kg at screening and CRU admission.
• BMI = weight (kg)/(height \[m\])2
• Subjects with Normal Renal Function (Cohorts 1 and 2):
• Subjects must have an eGFR (calculated using the CKD-EPI Equation) ≥ 60 mL/min/1.73 m2 consistent with the National Kidney Foundation stages 1 and 2 of CKD.
• Subjects must be otherwise healthy and without clinically significant abnormalities as assessed by review of medical and surgical history, physical examination, vital signs measurement, pulse oximetry, ECG, and clinical laboratory evaluations conducted at screening and CRU admission. A single repeat measurement/test may be performed, at the discretion of the physician, to confirm vital signs, pulse oximetry, ECG, and clinical laboratory tests abnormalities (ie, to confirm that a subject is eligible).
• Patients with Renal Impairment (Cohorts 3 and 4):
• Patients in Cohort 3 must have an eGFR (calculated using the CKD-EPI Equation) ≥ 30 and \< 60 mL/min/1.73 m2 consistent with the National Kidney Foundation stages 3a and 3b of CKD.
• Patients in Cohort 4 must have an eGFR (calculated using the CKD-EPI Equation) ≥ 15 and \< 30 mL/min/1.73 m2 consistent with the National Kidney Foundation stage 4 of CKD.

You may not qualify if:

• All Subjects/Patients:
• Female subject/patient is pregnant or breastfeeding.
• History or presence of conditions which, in the judgment of the investigator, are known to interfere with the distribution, metabolism, or excretion of drugs.
• History or presence of conditions that may place the subject at increased risk as determined by the investigator.
• History of surgery or major trauma within 12 weeks of screening, or surgery planned during the study.
• History of alcohol abuse, illicit drug use, significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction within 6 months of screening.
• Systolic blood pressure (BP) \< 90 or \> 160 mmHg or diastolic BP \< 50 or \> 100 mmHg measured after the subject has been resting quietly in a supine position or in the most recumbent position possible for at least 5 minutes at screening or CRU admission. A single repeat measurement may be performed to confirm vital signs abnormalities (ie, to confirm that a subject is eligible).
• Heart rate (HR) \< 40 or \> 105 beats per minute (bpm) measured on ECG after the subject has been resting quietly in a supine position or in the most recumbent position possible for at least 5 minutes at screening or CRU admission. A single repeat measurement may be performed to confirm ECG abnormalities (ie, to confirm that a subject is eligible).
• Has taken other investigational drugs or participated in any clinical study within 30 days or 5 half-lives of the investigational drug's PK, PD, or biological activity, whichever is longer, prior to first dose of study drug in this study.
• Prior exposure to VFI or known allergy to dextrans.
• History of any clinically significant allergic or negative reactions, side effects, or anaphylaxis to iodine, dyes, shellfish, isotopes, or dextran molecules.
• Significant blood loss (\> 450 mL) or has donated 1 or more units of blood or plasma within 6 weeks prior to study participation.
• Positive screen for human immunodeficiency virus (HIV)-1 or HIV-2 antibodies, hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.
• Diagnosis of acquired immune deficiency syndrome (AIDS).
• History of nephrectomy or kidney transplant.

Sponsors & Collaborators

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

Study Sites (2)

University of Alabama Birmingham, Division of Nephrology

Birmingham, Alabama, 35294, United States

Location

ICON Early Phase Services, LLC

San Antonio, Texas, 78209, United States

Location

MeSH Terms

Conditions

Kidney Diseases; Renal Insufficiency, Chronic; Acute Kidney Injury; Urologic Diseases; Renal Insufficiency

Condition Hierarchy (Ancestors)

Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Emmanuel DeNoia, MD

  ICON Early Phase Services, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2017
• First Posted: March 29, 2017
• Study Start: June 13, 2017
• Primary Completion: September 20, 2017
• Study Completion: September 20, 2017
• Last Updated: December 26, 2018

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)