Back to resultsPharmacokinetics of MB-102 and Use of the Non-invasive Optical Renal Function Monitor (ORFM) Device in Subjects With Normal and Impaired Renal Function and a Range of Skin Color Types
Primary Purpose
Acute Kidney Injury
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
MB-102-- single dose
MB-102-- two doses
Iohexol
QuantumLeap
Radiance
Brilliance
Sponsored by
About this trial
This is an interventional basic science trial for Acute Kidney Injury focused on measuring Glomerular Filtration Rate
Eligibility Criteria
Inclusion Criteria:
- Normal-CKD Stage 2/QuantumLeap; CKD Stage 3-4/QuantumLeap; Normal-CKD Stage 2/Radiance; and CKD Stage 3-5/Radiance groups: Age ≥ 22 years
- Normal-CKD Stage 2/Brilliance algorithm optimization; CKD Stage 3-5/Brilliance algorithm optimization; Normal-CKD Stage 2/Brilliance sensor optimization; Normal-CKD Stage 2/Brilliance sensor validation; CKD Stage 3-5/Brilliance sensor validation; Normal-CKD Stage 2/Brilliance final algorithm and sensor; CKD Stage 3-5/Brilliance final algorithm and sensor groups: Age ≥ 18 years
- Female participants must not be of child-bearing potential or willing to use study-designated contraception methods from screening through the follow-up visit
- Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 7 days post-dose
- Normal or non-clinically significant screening and baseline 12 lead ECG in the opinion of the PI
- Adequate venous access sufficient to allow blood sampling per protocol requirements
Normal-CKD Stage 2/QuantumLeap; Normal-CKD Stage 2/Radiance; Normal-CKD Stage 2/Brilliance algorithm optimization; Normal-CKD Stage 2/Brilliance sensor optimization; Normal-CKD Stage 2/Brilliance sensor validation; and Normal-CKD Stage 2/Brilliance final algorithm and sensor groups:
- Healthy as determined by medical history, with no clinically significant findings on screening and baseline physical exams, vital signs and clinical laboratory panels or conditions that could adversely impact the participant's participation or safety, conduct of the study or interfere with study assessments
- eGFR (CKD-EPI equation) of ≥60 mL/min/1.73m^2 (normal to Stage 2 CKD) at the time of screening
CKD Stage 3-4/QuantumLeap group:
- Stable renal function in the opinion of the PI
- eGFR (CKD-EPI equation) of 15 - 59 mL/min/1.73m^2 at the time of screening
- Stable use of immunosuppressant medications (when applicable)
CKD Stage 3-5/Radiance; CKD Stage 3-5/Brilliance algorithm optimization; CKD Stage 3-5/Brilliance sensor validation; and CKD Stage 3-5/Brilliance final algorithm and sensor groups:
- Possess stable renal function as defined as the most recent historical (within 3 months) eGFR and screening eGFR differing by ≤20%.
- eGFR (CKD-EPI equation) of <59 mL/min/1.73m^2 based on a historical value collected within 3 months or from the screening serum creatinine
- Stable use of immunosuppressant medications (when applicable) defined as no changes in the last 30 days or expected through the follow up visits, and a prednisone dose of <20 mg/day (or another steroid's equivalent dose)
Exclusion Criteria (Normal-CKD Stage 2/QuantumLeap and CKD Stage 3-4/QuantumLeap groups):
- Women who are pregnant, lactating or planning to become pregnant during the study, or women who are of childbearing potential unwilling to use a barrier method of birth control
- Intolerant to venipuncture
- Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication
- Participation in another interventional trial within 30 days of screening or concurrently enrolled in any other medical research study which could impact the results of the study
- History of drug or alcohol abuse within the past year
- History of allergy or hypersensitivity to MB-102 or iohexol, or other related (iodinated contrast media) products, or any of the inactive ingredients
- History of skin sensitivity to adhesives (e.g. Band-Aids, surgical tape)
- Any food allergy, intolerance, restriction or special diet that, in the opinion of the Principal Investigator, could contraindicate the subject's participation in this study
- Subjects who have allergies to 2 or more classes of drugs. (Intolerance to a drug is not considered a drug allergy)
- Stable use (no changes within 30 days) of prescription or OTC medications
- NSAID use within 2 days of dosing day
- History of coagulation disorders or bleeding disorders that in the judgement of the investigator places the subject at undue risks for study related procedures
- Are homozygous for sickle cell disease
- Have a known thyroid disorder
- Have pheochromocytoma
- Currently on Coumadin (warfarin) who have an INR>4 at Screening
- Current history of AIDS or HIV
- Hepatitis B antigen positive, or C antibody positive
- Site personnel immediately associated with the study or their immediate family members
- Any characteristics which, in the opinion of the investigator, makes the subject a poor candidate for participation in the clinical trial
- Prior enrollment and dosing in this Pilot 2 study
- Significant scarring, tattoos or alterations in pigmentation on the sternum that would alter sensor readings versus other areas of the skin
Additional Exclusion Criteria: (Normal-CKD Stage 2/QuantumLeap group):
- History of significant cardiovascular disease, heart failure, myocardial infarction in the past 3 months, pulmonary, hematologic, endocrine, hepatobiliary, nephrologic, immunologic, dermatologic, neurologic (including any history of stroke and/or seizure disorder), psychological, musculoskeletal disease, diagnosis of cancer with the past 2 years or deemed clinically significant or unstable by the Principal Investigator; Note: history of gallstones or kidney stones are not excluded so long as the condition is not acute within 30 days of dosing.
Additional Exclusion Criteria (CKD Stage 3-4/QuantumLeap group):
- Stage 5 CKD at the time of screening
- Recent (within 3 months) significant medical condition or surgical procedure including myocardial infarction, laparoscopic procedures, or other medical inventions
- Doses of prednisone greater than 10 mg/day within the last 90 days
Exclusion Criteria (Normal-CKD Stage 2/Radiance and CKD Stage 3-5/Radiance groups):
Women who are pregnant, lactating or planning to become pregnant during the study, or women who are of childbearing potential unwilling to use a barrier method of birth control
• Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 7 days post dose
- Unable to have venous access placed in both arms
- Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication
- Participation in another interventional trial within 30 days of dosing or concurrently enrolled in any other medical research study which could impact the results of the study
- History of drug or alcohol abuse within the past year
- History of skin sensitivity to adhesives (e.g. Band-Aids, surgical tape)
- History of severe allergic hypersensitivity reactions (unacceptable adverse events) or anaphylactoid reaction to any allergen including drugs, MB102 and iohexol or other related (iodinated contrast media) products (intolerance to a drug is not considered a drug allergy).
- NSAID use within 2 days of dosing day
- History of coagulation disorders or bleeding disorders that in the judgement of the investigator places the subject at undue risks for study related procedures
- Are homozygous for sickle cell disease
- Have hyperthyroidism or current thyroid cancer
- Have pheochromocytoma
- Currently on Coumadin (warfarin) who have an INR>4 at Screening
- Current history of AIDS or HIV
- Current evidence of an active Hepatitis B or C infection. If the subject is Hepatitis C antibody positive, but the hepatitis C RNA is below the level of detection, they are considered immune and may be eligible for enrollment.
- Site personnel immediately associated with the study or their immediate family members
- Any characteristics which, in the opinion of the investigator, makes the subject a poor candidate for participation in the clinical trial
- Prior exposure to MB-102
- Significant scarring, tattoos or alterations in pigmentation on the sternum that would alter sensor readings versus other areas of the skin
Exclusion Criteria (Normal-CKD Stage 2/Brilliance algorithm optimization; CKD Stage 3-5/Brilliance algorithm optimization; Normal-CKD Stage 2/Brilliance final algorithm and sensor; and CKD Stage 3-5/Brilliance final algorithm and sensor groups):
Women who are pregnant, lactating or planning to become pregnant during the study, or women who are of childbearing potential unwilling to use a barrier method of birth control
• Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 7 days post dose
- Unable to have venous access
- Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication
- Participation in another interventional trial within 30 days of dosing or concurrently enrolled in any other medical research study which could impact the results of the study
- History of drug or alcohol abuse within the past year
- History of skin sensitivity to adhesives (e.g. Band-Aids, surgical tape)
- History of severe allergic hypersensitivity reactions (unacceptable adverse events) or anaphylactoid reaction to any allergen including drugs, or MB-102 (intolerance to a drug is not considered a drug allergy).
- NSAID use within 2 days of dosing day
- History of coagulation disorders or bleeding disorders that in the judgement of the investigator places the subject at undue risks for study related procedures
- Currently on Coumadin (warfarin) who have an INR>4 at Screening
- Current history of AIDS or HIV
- Current evidence of an active Hepatitis B or C infection. If the subject is Hepatitis C antibody positive, but the hepatitis C RNA is below the level of detection, they are considered immune and are be eligible for enrollment.
- Site personnel immediately associated with the study or their immediate family members
- Any characteristics which, in the opinion of the investigator, makes the subject a poor candidate for participation in the clinical trial
- Prior exposure to MB-102
- Significant scarring, tattoos or alterations in pigmentation on the sternum that would alter sensor readings versus other areas of the skin
Additional Exclusion Criteria: (Normal-CKD Stage 2/Radiance; Normal-CKD Stage 2/Brilliance algorithm optimization; Normal-CKD Stage 2/Brilliance sensor optimization; Normal-CKD Stage 2/Brilliance sensor validation; and Normal-CKD Stage 2/Brilliance final algorithm and sensor groups):
- History of significant cardiovascular disease, heart failure, myocardial infarction in the past 3 months, or NYHA class III or IV HF
- Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, or psychiatric condition that in the opinion of the investigator would limit the subjects' ability to complete study requirements or may put the subject at increased risk or compromise interpretability of study results. Note: a history of gallstones or kidney stones are not excluded so long as the condition is not acute within 30 days of dosing.
Additional Exclusion Criteria: (CKD Stage 3-5/Radiance; CKD Stage 3-5/Brilliance algorithm optimization; CKD Stage 3-5/Brilliance sensor validation; and CKD Stage 3-5/Brilliance final algorithm and sensor groups):
- Recent (within 3 months) significant medical condition or surgical procedure including myocardial infarction, thoracic laparoscopic procedures, or other significant medical inventions
- Received >20 mg/day of prednisone or an equivalent dose of glucocorticoid for more than 7 days in the last 90 days prior to dosing day for an acute or chronic disorder
- Currently receiving dialysis
- Currently anuric
Sites / Locations
- Riverside Clinical Research
- Orlando Clinical Research Center
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Normal-CKD Stage 2/QuantumLeap
CKD Stage 3-4/QuantumLeap
Normal-CKD Stage 2/Radiance
CKD Stage 3-5/Radiance
Normal-CKD Stage 2/Brilliance algorithm optimization
CKD Stage 3-5/Brilliance algorithm optimization
Normal-CKD Stage 2/Brilliance sensor optimization
Normal-CKD Stage 2/Brilliance sensor verification
CKD Stage 3-5/Brilliance sensor verification
Normal-CKD Stage 2/Brilliance final algorithm and sensor
CKD Stage 3-5/Brilliance final algorithm and sensor
Arm Description
MB-102 and iohexol administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the QuantumLeap ORFM device. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. In order to determine the optimal dose of MB-102, participants may receive different doses.
MB-102 and iohexol administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-4), and fluorescence measured by the QuantumLeap ORFM device. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. In order to determine the optimal dose of MB-102, participants may receive different doses.
MB-102 and iohexol administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Radiance ORFM device. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
MB-102 and iohexol administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Radiance ORFM device. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. Algorithm optimization of the Brilliance sensor will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
MB-102 administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Brilliance ORFM device. Algorithm optimization of the Brilliance sensor will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. Sensor optimization of the Brilliance device will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. Verification of the Brilliance sensor will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
MB-102 administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Brilliance ORFM device. Verification of the Brilliance sensor will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. The optimized algorithm and final device design of the Brilliance device will be tested. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. A subset of participants in this arm will receive two doses of MB-102, 12 hours apart.
MB-102 administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Brilliance ORFM device. The optimized algorithm and final device design of the Brilliance device will be tested. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Outcomes
Primary Outcome Measures
Incidence of Treatment-Emergent Adverse Events
The assessment of safety will be based primarily on the frequency of adverse events and on the number of laboratory values that fall outside of pre-specified normal ranges. The clinical significance of any abnormal findings will be determined by the principal investigators. All safety data including Adverse Events (AEs), vital signs, electrocardiograms (ECGs), and physical examinations will be listed by participant.
Secondary Outcome Measures
Maximum Plasma Concentration (Cmax) for MB-102 and iohexol
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) will be directly determined from the concentration-time data.
Time to Maximum Plasma Concentration (Tmax) for MB-102 and iohexol
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) will be directly determined from the concentration-time data.
The terminal rate constant for MB-102 and iohexol
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The terminal rate constant (λz) will be determined by linear regression of the terminal linear phase of the log plasma concentration-time profile.
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration for MB-102 and iohexol
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng*hr/mL) will be estimated from time 0 to the last measureable concentration using noncompartmental analyses.
Area under the plasma concentration-time curve from time zero to infinity for MB-102 and iohexol
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng*hr/mL) from time 0 to infinity will be calculated as: AUC∞ = AUClast + LQC/λz where LQC is the predicted concentration (based on the terminal regression) at the time of the last measurable concentration.
The elimination half-life of MB-102 and iohexol
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The elimination half-life (the time required for the concentration of the drug to reach half of its original value) will be calculated as t1/2 λz= ln(2)/ λz.
Total plasma clearance of MB-102 and iohexol
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Total plasma clearance (the volume of plasma cleared of the drug over time) will be calculated as: Clp = Dose/ AUC∞.
Renal clearance of MB-102 and iohexol
Urine samples will be collected pre-dose (time 0) and 5 mL urine samples will be collected each time the subject voids. The total volume of urine excreted will be recorded until 12 hours post-dose, and will be analyzed using validated analytical methods. Renal clearance (the volume of plasma cleared of the drug by the kidneys over time) will be calculated as: CLr = Ae/ AUClast, where Ae is the cumulative amount of analyte excreted in urine over the sampling interval.
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Quantum Leap device and plasma concentration of MB-102 at each time point in the renal excretion phase
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the QuantumLeap device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the QuantumLeap device and the plasma concentration of MB-102 at each time point in the renal excretion phase will be calculated.
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Quantum Leap device and plasma concentration of iohexol at each time point in the renal excretion phase
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the QuantumLeap device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Quantum Leap device and the plasma concentration of iohexol at each time point in the renal excretion phase will be calculated.
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Radiance device and plasma concentration of MB-102 at each time point in the renal excretion phase
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the Radiance device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Radiance device and the plasma concentration of MB-102 at each time point in the renal excretion phase will be calculated.
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Radiance device and plasma concentration of iohexol at each time point in the renal excretion phase
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the Radiance device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Radiance device and the plasma concentration of iohexol at each time point in the renal excretion phase will be calculated.
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Brilliance device and plasma concentration of MB-102 at each time point in the renal excretion phase in participants with normal-CKD Stage 2 renal function
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, and 480 minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the Brilliance device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Brilliance device and the plasma concentration of MB-102 at each time point in the renal excretion phase will be calculated.
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Brilliance device and plasma concentration of MB-102 at each time point in the renal excretion phase in participants with CKD Stage 3-5 renal function
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) and 960, 1440, 1920, 2400, and 2880 (±30 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the Brilliance device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Brilliance device and the plasma concentration of MB-102 at each time point in the renal excretion phase will be calculated.
Number of participants with adverse events related to the use of the QuantumLeap device
The number of participants with adverse events related to the use of the QuantumLeap device was documented.
Number of participants with adverse events related to the use of the Radiance device
The number of participants with adverse events related to the use of the Radiance device was documented.
Number of participants with adverse events related to the use of the Brilliance device
The number of participants with adverse events related to the use of the Brilliance device was documented.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02772276
Brief Title
Pharmacokinetics of MB-102 and Use of the Non-invasive Optical Renal Function Monitor (ORFM) Device in Subjects With Normal and Impaired Renal Function and a Range of Skin Color Types
Official Title
A Pilot Safety and Pharmacokinetic Study of MB-102 Versus Iohexol and the Use of the Non-invasive Optical Renal Function Monitor (ORFM) Device in Subjects With Normal and Impaired Renal Function and a Range of Skin Color Types
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
July 12, 2016 (Actual)
Primary Completion Date
August 4, 2021 (Actual)
Study Completion Date
August 4, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MediBeacon
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a pilot, safety, and pharmacokinetic study of MB-102 versus iohexol and the use of the non-invasive optical renal function monitor (ORFM) device in normal and compromised renal function participants with different skin color types.
Detailed Description
The objectives of this study are to evaluate the safety and tolerability of single and multiple doses of MB-102 in participants with normal and impaired kidney function; to determine plasma pharmacokinetics of MB-102 compared to the pharmacokinetics of iohexol in participants with normal and impaired kidney function; to demonstrate that MB-102-transdermal-fluorescence-measured glomerular filtration rate (GFR) using the optical renal function monitor (ORFM) Brilliance device is aligned with MB-102 plasma GFR; to evaluate the safety and effectiveness of the ORFM investigational medical device prototypes QuantumLeap, Radiance, and Brilliance for the non-invasive transdermal fluorescent detection of MB-102 in participants with a range of skin color types; and to determine the optimal dose of MB-102 for non-invasive measurement.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury
Keywords
Glomerular Filtration Rate
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
245 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Normal-CKD Stage 2/QuantumLeap
Arm Type
Experimental
Arm Description
MB-102 and iohexol administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the QuantumLeap ORFM device. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. In order to determine the optimal dose of MB-102, participants may receive different doses.
Arm Title
CKD Stage 3-4/QuantumLeap
Arm Type
Experimental
Arm Description
MB-102 and iohexol administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-4), and fluorescence measured by the QuantumLeap ORFM device. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. In order to determine the optimal dose of MB-102, participants may receive different doses.
Arm Title
Normal-CKD Stage 2/Radiance
Arm Type
Experimental
Arm Description
MB-102 and iohexol administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Radiance ORFM device. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Arm Title
CKD Stage 3-5/Radiance
Arm Type
Experimental
Arm Description
MB-102 and iohexol administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Radiance ORFM device. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Arm Title
Normal-CKD Stage 2/Brilliance algorithm optimization
Arm Type
Experimental
Arm Description
MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. Algorithm optimization of the Brilliance sensor will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Arm Title
CKD Stage 3-5/Brilliance algorithm optimization
Arm Type
Experimental
Arm Description
MB-102 administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Brilliance ORFM device. Algorithm optimization of the Brilliance sensor will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Arm Title
Normal-CKD Stage 2/Brilliance sensor optimization
Arm Type
Experimental
Arm Description
MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. Sensor optimization of the Brilliance device will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Arm Title
Normal-CKD Stage 2/Brilliance sensor verification
Arm Type
Experimental
Arm Description
MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. Verification of the Brilliance sensor will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Arm Title
CKD Stage 3-5/Brilliance sensor verification
Arm Type
Experimental
Arm Description
MB-102 administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Brilliance ORFM device. Verification of the Brilliance sensor will be conducted. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Arm Title
Normal-CKD Stage 2/Brilliance final algorithm and sensor
Arm Type
Experimental
Arm Description
MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. The optimized algorithm and final device design of the Brilliance device will be tested. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. A subset of participants in this arm will receive two doses of MB-102, 12 hours apart.
Arm Title
CKD Stage 3-5/Brilliance final algorithm and sensor
Arm Type
Experimental
Arm Description
MB-102 administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Brilliance ORFM device. The optimized algorithm and final device design of the Brilliance device will be tested. Approximately half of the participants will be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Intervention Type
Drug
Intervention Name(s)
MB-102-- single dose
Intervention Description
4 µmol/kg administered by intravenous injection over 30 seconds, followed by a 10 mL normal saline flush administered intravenously over 30 seconds.
Intervention Type
Drug
Intervention Name(s)
MB-102-- two doses
Intervention Description
4 µmol/kg administered by intravenous injection over 30 seconds, followed by a 10 mL normal saline flush administered intravenously over 30 seconds. A subset of participants will receive two doses of MB-102, 12 hours apart.
Intervention Type
Drug
Intervention Name(s)
Iohexol
Other Intervention Name(s)
Omnipaque 300
Intervention Description
5 mL of a 647 mg/mL solution administered by intravenous injection over 30 seconds, followed by a 10 mL normal saline flush administered intravenously over 30 seconds
Intervention Type
Device
Intervention Name(s)
QuantumLeap
Intervention Description
Optical Renal Function Monitor (ORFM)
Intervention Type
Device
Intervention Name(s)
Radiance
Intervention Description
Optical Renal Function Monitor (ORFM)
Intervention Type
Device
Intervention Name(s)
Brilliance
Intervention Description
Optical Renal Function Monitor (ORFM)
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
The assessment of safety will be based primarily on the frequency of adverse events and on the number of laboratory values that fall outside of pre-specified normal ranges. The clinical significance of any abnormal findings will be determined by the principal investigators. All safety data including Adverse Events (AEs), vital signs, electrocardiograms (ECGs), and physical examinations will be listed by participant.
Time Frame
Up to 10 days following the final study dose
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) for MB-102 and iohexol
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) will be directly determined from the concentration-time data.
Time Frame
Pre-dose and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose.
Title
Time to Maximum Plasma Concentration (Tmax) for MB-102 and iohexol
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) will be directly determined from the concentration-time data.
Time Frame
Pre-dose and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose.
Title
The terminal rate constant for MB-102 and iohexol
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The terminal rate constant (λz) will be determined by linear regression of the terminal linear phase of the log plasma concentration-time profile.
Time Frame
Pre-dose and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose.
Title
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration for MB-102 and iohexol
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng*hr/mL) will be estimated from time 0 to the last measureable concentration using noncompartmental analyses.
Time Frame
Pre-dose and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose.
Title
Area under the plasma concentration-time curve from time zero to infinity for MB-102 and iohexol
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng*hr/mL) from time 0 to infinity will be calculated as: AUC∞ = AUClast + LQC/λz where LQC is the predicted concentration (based on the terminal regression) at the time of the last measurable concentration.
Time Frame
Pre-dose and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose.
Title
The elimination half-life of MB-102 and iohexol
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. The elimination half-life (the time required for the concentration of the drug to reach half of its original value) will be calculated as t1/2 λz= ln(2)/ λz.
Time Frame
Pre-dose and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose.
Title
Total plasma clearance of MB-102 and iohexol
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Total plasma clearance (the volume of plasma cleared of the drug over time) will be calculated as: Clp = Dose/ AUC∞.
Time Frame
Pre-dose and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose.
Title
Renal clearance of MB-102 and iohexol
Description
Urine samples will be collected pre-dose (time 0) and 5 mL urine samples will be collected each time the subject voids. The total volume of urine excreted will be recorded until 12 hours post-dose, and will be analyzed using validated analytical methods. Renal clearance (the volume of plasma cleared of the drug by the kidneys over time) will be calculated as: CLr = Ae/ AUClast, where Ae is the cumulative amount of analyte excreted in urine over the sampling interval.
Time Frame
Pre-dose and each time the participant voids up to 720 minutes post dose
Title
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Quantum Leap device and plasma concentration of MB-102 at each time point in the renal excretion phase
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the QuantumLeap device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the QuantumLeap device and the plasma concentration of MB-102 at each time point in the renal excretion phase will be calculated.
Time Frame
Pre-dose (time 0) and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose
Title
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Quantum Leap device and plasma concentration of iohexol at each time point in the renal excretion phase
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the QuantumLeap device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Quantum Leap device and the plasma concentration of iohexol at each time point in the renal excretion phase will be calculated.
Time Frame
Pre-dose (time 0) and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose
Title
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Radiance device and plasma concentration of MB-102 at each time point in the renal excretion phase
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the Radiance device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Radiance device and the plasma concentration of MB-102 at each time point in the renal excretion phase will be calculated.
Time Frame
Pre-dose (time 0) and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose
Title
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Radiance device and plasma concentration of iohexol at each time point in the renal excretion phase
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the Radiance device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Radiance device and the plasma concentration of iohexol at each time point in the renal excretion phase will be calculated.
Time Frame
Pre-dose (time 0) and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) minutes post dose
Title
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Brilliance device and plasma concentration of MB-102 at each time point in the renal excretion phase in participants with normal-CKD Stage 2 renal function
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, and 480 minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the Brilliance device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Brilliance device and the plasma concentration of MB-102 at each time point in the renal excretion phase will be calculated.
Time Frame
Pre-dose (time 0) and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, and 480 minutes post dose
Title
Correlation between the transdermal fluorescence intensity of MB-102 as measured by the Brilliance device and plasma concentration of MB-102 at each time point in the renal excretion phase in participants with CKD Stage 3-5 renal function
Description
Blood samples will be collected pre-dose (time 0) and at 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) and 960, 1440, 1920, 2400, and 2880 (±30 min) minutes post dose, and will be analyzed using validated analytical methods. Transdermal fluorescence intensity at the time of blood sampling as measured by the Brilliance device will be documented, and the correlation between the transdermal fluorescence intensity of MB-102 as measured by the Brilliance device and the plasma concentration of MB-102 at each time point in the renal excretion phase will be calculated.
Time Frame
Pre-dose (time 0) and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 360, 480, 600 and 720 (±10 min) and 960, 1440, 1920, 2400, and 2880 (±30 min) minutes post dose
Title
Number of participants with adverse events related to the use of the QuantumLeap device
Description
The number of participants with adverse events related to the use of the QuantumLeap device was documented.
Time Frame
Pre-dose (time 0) up to 10 days post dose
Title
Number of participants with adverse events related to the use of the Radiance device
Description
The number of participants with adverse events related to the use of the Radiance device was documented.
Time Frame
Pre-dose (time 0) up to 10 days post dose
Title
Number of participants with adverse events related to the use of the Brilliance device
Description
The number of participants with adverse events related to the use of the Brilliance device was documented.
Time Frame
Pre-dose (time 0) up to 10 days post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Normal-CKD Stage 2/QuantumLeap; CKD Stage 3-4/QuantumLeap; Normal-CKD Stage 2/Radiance; and CKD Stage 3-5/Radiance groups: Age ≥ 22 years
Normal-CKD Stage 2/Brilliance algorithm optimization; CKD Stage 3-5/Brilliance algorithm optimization; Normal-CKD Stage 2/Brilliance sensor optimization; Normal-CKD Stage 2/Brilliance sensor validation; CKD Stage 3-5/Brilliance sensor validation; Normal-CKD Stage 2/Brilliance final algorithm and sensor; CKD Stage 3-5/Brilliance final algorithm and sensor groups: Age ≥ 18 years
Female participants must not be of child-bearing potential or willing to use study-designated contraception methods from screening through the follow-up visit
Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 7 days post-dose
Normal or non-clinically significant screening and baseline 12 lead ECG in the opinion of the PI
Adequate venous access sufficient to allow blood sampling per protocol requirements
Normal-CKD Stage 2/QuantumLeap; Normal-CKD Stage 2/Radiance; Normal-CKD Stage 2/Brilliance algorithm optimization; Normal-CKD Stage 2/Brilliance sensor optimization; Normal-CKD Stage 2/Brilliance sensor validation; and Normal-CKD Stage 2/Brilliance final algorithm and sensor groups:
Healthy as determined by medical history, with no clinically significant findings on screening and baseline physical exams, vital signs and clinical laboratory panels or conditions that could adversely impact the participant's participation or safety, conduct of the study or interfere with study assessments
eGFR (CKD-EPI equation) of ≥60 mL/min/1.73m^2 (normal to Stage 2 CKD) at the time of screening
CKD Stage 3-4/QuantumLeap group:
Stable renal function in the opinion of the PI
eGFR (CKD-EPI equation) of 15 - 59 mL/min/1.73m^2 at the time of screening
Stable use of immunosuppressant medications (when applicable)
CKD Stage 3-5/Radiance; CKD Stage 3-5/Brilliance algorithm optimization; CKD Stage 3-5/Brilliance sensor validation; and CKD Stage 3-5/Brilliance final algorithm and sensor groups:
Possess stable renal function as defined as the most recent historical (within 3 months) eGFR and screening eGFR differing by ≤20%.
eGFR (CKD-EPI equation) of <59 mL/min/1.73m^2 based on a historical value collected within 3 months or from the screening serum creatinine
Stable use of immunosuppressant medications (when applicable) defined as no changes in the last 30 days or expected through the follow up visits, and a prednisone dose of <20 mg/day (or another steroid's equivalent dose)
Exclusion Criteria (Normal-CKD Stage 2/QuantumLeap and CKD Stage 3-4/QuantumLeap groups):
Women who are pregnant, lactating or planning to become pregnant during the study, or women who are of childbearing potential unwilling to use a barrier method of birth control
Intolerant to venipuncture
Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication
Participation in another interventional trial within 30 days of screening or concurrently enrolled in any other medical research study which could impact the results of the study
History of drug or alcohol abuse within the past year
History of allergy or hypersensitivity to MB-102 or iohexol, or other related (iodinated contrast media) products, or any of the inactive ingredients
History of skin sensitivity to adhesives (e.g. Band-Aids, surgical tape)
Any food allergy, intolerance, restriction or special diet that, in the opinion of the Principal Investigator, could contraindicate the subject's participation in this study
Subjects who have allergies to 2 or more classes of drugs. (Intolerance to a drug is not considered a drug allergy)
Stable use (no changes within 30 days) of prescription or OTC medications
NSAID use within 2 days of dosing day
History of coagulation disorders or bleeding disorders that in the judgement of the investigator places the subject at undue risks for study related procedures
Are homozygous for sickle cell disease
Have a known thyroid disorder
Have pheochromocytoma
Currently on Coumadin (warfarin) who have an INR>4 at Screening
Current history of AIDS or HIV
Hepatitis B antigen positive, or C antibody positive
Site personnel immediately associated with the study or their immediate family members
Any characteristics which, in the opinion of the investigator, makes the subject a poor candidate for participation in the clinical trial
Prior enrollment and dosing in this Pilot 2 study
Significant scarring, tattoos or alterations in pigmentation on the sternum that would alter sensor readings versus other areas of the skin
Additional Exclusion Criteria: (Normal-CKD Stage 2/QuantumLeap group):
- History of significant cardiovascular disease, heart failure, myocardial infarction in the past 3 months, pulmonary, hematologic, endocrine, hepatobiliary, nephrologic, immunologic, dermatologic, neurologic (including any history of stroke and/or seizure disorder), psychological, musculoskeletal disease, diagnosis of cancer with the past 2 years or deemed clinically significant or unstable by the Principal Investigator; Note: history of gallstones or kidney stones are not excluded so long as the condition is not acute within 30 days of dosing.
Additional Exclusion Criteria (CKD Stage 3-4/QuantumLeap group):
Stage 5 CKD at the time of screening
Recent (within 3 months) significant medical condition or surgical procedure including myocardial infarction, laparoscopic procedures, or other medical inventions
Doses of prednisone greater than 10 mg/day within the last 90 days
Exclusion Criteria (Normal-CKD Stage 2/Radiance and CKD Stage 3-5/Radiance groups):
Women who are pregnant, lactating or planning to become pregnant during the study, or women who are of childbearing potential unwilling to use a barrier method of birth control
• Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 7 days post dose
Unable to have venous access placed in both arms
Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication
Participation in another interventional trial within 30 days of dosing or concurrently enrolled in any other medical research study which could impact the results of the study
History of drug or alcohol abuse within the past year
History of skin sensitivity to adhesives (e.g. Band-Aids, surgical tape)
History of severe allergic hypersensitivity reactions (unacceptable adverse events) or anaphylactoid reaction to any allergen including drugs, MB102 and iohexol or other related (iodinated contrast media) products (intolerance to a drug is not considered a drug allergy).
NSAID use within 2 days of dosing day
History of coagulation disorders or bleeding disorders that in the judgement of the investigator places the subject at undue risks for study related procedures
Are homozygous for sickle cell disease
Have hyperthyroidism or current thyroid cancer
Have pheochromocytoma
Currently on Coumadin (warfarin) who have an INR>4 at Screening
Current history of AIDS or HIV
Current evidence of an active Hepatitis B or C infection. If the subject is Hepatitis C antibody positive, but the hepatitis C RNA is below the level of detection, they are considered immune and may be eligible for enrollment.
Site personnel immediately associated with the study or their immediate family members
Any characteristics which, in the opinion of the investigator, makes the subject a poor candidate for participation in the clinical trial
Prior exposure to MB-102
Significant scarring, tattoos or alterations in pigmentation on the sternum that would alter sensor readings versus other areas of the skin
Exclusion Criteria (Normal-CKD Stage 2/Brilliance algorithm optimization; CKD Stage 3-5/Brilliance algorithm optimization; Normal-CKD Stage 2/Brilliance final algorithm and sensor; and CKD Stage 3-5/Brilliance final algorithm and sensor groups):
Women who are pregnant, lactating or planning to become pregnant during the study, or women who are of childbearing potential unwilling to use a barrier method of birth control
• Males must be willing to practice abstinence or utilize adequate contraception from dosing day to at least 7 days post dose
Unable to have venous access
Recent donation or loss of blood or plasma: 100 mL to 499 mL within 30 days prior to the initial dose of the study medication; or more than 499 mL within 56 days prior to the initial dose of study medication
Participation in another interventional trial within 30 days of dosing or concurrently enrolled in any other medical research study which could impact the results of the study
History of drug or alcohol abuse within the past year
History of skin sensitivity to adhesives (e.g. Band-Aids, surgical tape)
History of severe allergic hypersensitivity reactions (unacceptable adverse events) or anaphylactoid reaction to any allergen including drugs, or MB-102 (intolerance to a drug is not considered a drug allergy).
NSAID use within 2 days of dosing day
History of coagulation disorders or bleeding disorders that in the judgement of the investigator places the subject at undue risks for study related procedures
Currently on Coumadin (warfarin) who have an INR>4 at Screening
Current history of AIDS or HIV
Current evidence of an active Hepatitis B or C infection. If the subject is Hepatitis C antibody positive, but the hepatitis C RNA is below the level of detection, they are considered immune and are be eligible for enrollment.
Site personnel immediately associated with the study or their immediate family members
Any characteristics which, in the opinion of the investigator, makes the subject a poor candidate for participation in the clinical trial
Prior exposure to MB-102
Significant scarring, tattoos or alterations in pigmentation on the sternum that would alter sensor readings versus other areas of the skin
Additional Exclusion Criteria: (Normal-CKD Stage 2/Radiance; Normal-CKD Stage 2/Brilliance algorithm optimization; Normal-CKD Stage 2/Brilliance sensor optimization; Normal-CKD Stage 2/Brilliance sensor validation; and Normal-CKD Stage 2/Brilliance final algorithm and sensor groups):
History of significant cardiovascular disease, heart failure, myocardial infarction in the past 3 months, or NYHA class III or IV HF
Any other serious or uncontrolled medical disorder, active infection, physical exam finding, laboratory finding, or psychiatric condition that in the opinion of the investigator would limit the subjects' ability to complete study requirements or may put the subject at increased risk or compromise interpretability of study results. Note: a history of gallstones or kidney stones are not excluded so long as the condition is not acute within 30 days of dosing.
Additional Exclusion Criteria: (CKD Stage 3-5/Radiance; CKD Stage 3-5/Brilliance algorithm optimization; CKD Stage 3-5/Brilliance sensor validation; and CKD Stage 3-5/Brilliance final algorithm and sensor groups):
Recent (within 3 months) significant medical condition or surgical procedure including myocardial infarction, thoracic laparoscopic procedures, or other significant medical inventions
Received >20 mg/day of prednisone or an equivalent dose of glucocorticoid for more than 7 days in the last 90 days prior to dosing day for an acute or chronic disorder
Currently receiving dialysis
Currently anuric
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard B Dorshow, PhD
Organizational Affiliation
MediBeacon, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Riverside Clinical Research
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32132
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Pharmacokinetics of MB-102 and Use of the Non-invasive Optical Renal Function Monitor (ORFM) Device in Subjects With Normal and Impaired Renal Function and a Range of Skin Color Types
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