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
Condition: Acute Kidney Injury
MeSH terms: Acute Kidney Injury; Renal Insufficiency
Intervention: MB-102-- single dose of 4 µmol/kg; MB-102-- single dose of 130 mg; MB-102-single dose of 130 mg or 2 doses of 130 mg 12 hours apart; MB-102-- two doses of 130 mg 24 hours apart; Iohexol; QuantumLeap; Radiance; Brilliance (1 or 2 sensors); Brilliance (2-part sensor)
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.; 130 mg 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.; 130 mg administered by intravenous injection over 30 seconds, followed by a 10 mL normal saline flush administered intravenously over 30 seconds.; 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.; 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; Optical Renal Function Monitor (ORFM); Optical Renal Function Monitor (ORFM); Optical Renal Function Monitor (ORFM); Optical Renal Function Monitor (ORFM)
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 234.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Glomerular Filtration Rate

Summary:

      This study was 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.
    

Eligibility criteria:

        INCLUSION CRITERIA

        Main Criteria for Inclusion (Quantum Leap and Radiance device)

          -  Age > 22 years - male or female

               -  Eligible female non-pregnant participants who are either not of childbearing
                  potential or willing to use adequate contraception during the trial

               -  Males must be willing to practice abstinence or utilize adequate contraception
                  from dosing day to at least 7 days post dose

          -  Participants willing to comply with study requirements

          -  Participants who have signed an informed consent form

          -  Normal or non-clinically significant screening and baseline 12-lead electrocardiogram
             (ECG) in the opinion of the principal investigator (PI)

          -  Adequate venous access sufficient to allow blood sampling per protocol requirements

        Main Criteria for Inclusion (Brilliance device)

          -  Age > 18 years - male or female

               -  Eligible female non-pregnant participants who are either not of childbearing
                  potential or willing to use adequate contraception during the trial

               -  Males must be willing to practice abstinence or utilize adequate contraception
                  from dosing day to at least 7 days post dose

          -  Participants willing to comply with study requirements

          -  Participants who have signed an informed consent form

          -  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 optimization; and Normal-CKD Stage 2/Brilliance (1-2 sensors)

          -  Are 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

          -  Have estimated glomerular filtration rate (eGFR (Chronic kidney disease - epidemiology
             collaboration [CKD-EPI] equation) of ≥60 ml/min/1.73m^2 (normal to Stage 2 CKD) at the
             time of screening

          -  Approximately half of the participants enrolled in each cohort to have Fitzpatrick
             Scale Type I, II or III skin color type

          -  Approximately half of the participants enrolled in each cohort to have Fitzpatrick
             Type IV, V or VI skin color type.

        CKD Stage 3-4/QuantumLeap

          -  Possess stable renal function in the opinion of the PI

          -  Have eGFR (CKD-EPI equation) of 15 - 59 mL/min/1.73m^2 at the time of screening

          -  Stable use of immunosuppressant medications (when applicable)

               -  15 participants per cohort to have Fitzpatrick Type I, II or III skin color type

               -  15 participants per cohort to have Fitzpatrick Type IV, V or VI skin color type

        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 1-2 sensors

          -  Possess stable renal function as defined as the most recent historical (within 3
             months) eGFR and screening eGFR differing by ≤20%.

          -  Have 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)

          -  Approximately half of the participants in each cohort to have Fitzpatrick Type I, II
             or III skin color type

          -  Approximately half of the participants in each cohort to have Fitzpatrick Type IV, V
             or VI skin color type

        EXCLUSION CRITERIA

        Main Criteria for Exclusion (QuantumLeap device)

          -  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
             PI, could contraindicate the subject's participation in this study

          -  Participants 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 over the counter (OTC)
             medications

          -  Non-steroidal anti-inflammatory drug (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 International normalized ratio (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 participant a
             poor candidate for participation in the clinical trial

          -  Prior enrollment and dosing in this Pilot 2 study

          -  Significant scaring, tattoos or alterations in pigmentation on the sternum that would
             alter sensor readings versus other areas of the skin

        Additional Exclusion: Normal-CKD Stage 2/QuantumLeap

        • 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: CKD Stage 3-4/QuantumLeap

          -  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

        Main Criteria for Exclusion: (Radiance device)

          -  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

             o 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, MB-102 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 participant 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 scaring, tattoos or alterations in pigmentation on the sternum that would
             alter sensor readings versus other areas of the skin

        Main Criteria for Exclusion: (Brilliance device)

          -  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

             o Males must be unwilling 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 participant 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 participant a
             poor candidate for participation in the clinical trial

          -  Significant scaring, tattoos or alterations in pigmentation on the sternum that would
             alter sensor readings versus other areas of the skin

        Additional Exclusion: 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 (1-2 sensors)

          -  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 participant's 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: 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 1-2
        sensors

          -  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