Clinical trial NCT02772276: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Kidney Injury
Keywords: Glomerular Filtration Rate
Lead sponsor: MediBeacon
Sponsor class: INDUSTRY
First posted: 2016-05-13
Enrollment: 234
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

Detailed description: The objectives of this study were 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.

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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: From the time of dosing through the follow-up visit, up to 10 days
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of MB-102
timeFrame: 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.
measure: Maximum Plasma Concentration (Cmax) of Iohexol
timeFrame: 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.
measure: Time to Maximum Plasma Concentration (Tmax) of MB-102
timeFrame: 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.
measure: Time to Maximum Plasma Concentration (Tmax) of Iohexol
timeFrame: 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.
measure: The Elimination Half-life of MB-102
timeFrame: 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.
measure: The Elimination Half-life of Iohexol
timeFrame: 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.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration for MB-102
timeFrame: 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.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration for Iohexol
timeFrame: 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.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity for MB-102
timeFrame: 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.
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity for Iohexol
timeFrame: 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.
measure: Total Plasma Clearance of MB-102
timeFrame: 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.
measure: Total Plasma Clearance of Iohexol
timeFrame: 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.
measure: The Terminal Rate Constant for MB-102
timeFrame: 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.
measure: The Terminal Rate Constant for Iohexol
timeFrame: 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.
measure: Renal Clearance of MB-102
timeFrame: Pre-dose and each time the participant voids up to 720 minutes post dose
measure: Renal Clearance of Iohexol
timeFrame: Pre-dose and each time the participant voids up to 720 minutes post dose
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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 3-4 Renal Function
timeFrame: 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
measure: Number of Participants With Adverse Events Related to the Use of the QuantumLeap Device
timeFrame: From the time of dosing through the follow-up visit, up to 10 days
measure: Number of Participants With Adverse Events Related to the Use of the Radiance Device
timeFrame: From the time of dosing through the follow-up visit, up to 10 days
measure: Number of Participants With Adverse Events Related to the Use of the Brilliance Device
timeFrame: From the time of dosing through the follow-up visit, up to 10 days
Other outcomes:
Locations:
city: Edgewater
country: United States
facility: Riverside Clinical Research
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: MediBeacon, Inc.
name: Richard B Dorshow, PhD
role: STUDY_DIRECTOR
References: