Clinical trial NCT02772276
Conditions: Acute Kidney Injury
Keywords: Glomerular Filtration Rate
Sponsor: MediBeacon
Start date: 2016-05-11; Completion date: 2021-08-04
Enrollment: 234 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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 were to 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 have received different doses. arm 2: 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 were to 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 have received different doses. arm 3: 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 were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. arm 4: 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 were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. arm 5: 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 was conducted. Approximately half of the participants were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. arm 6: 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 was conducted. Approximately half of the participants were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. arm 7: 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 was conducted. Approximately half of the participants were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. arm 8: MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device. Validation of the Brilliance sensor was conducted. Approximately half of the participants were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. arm 9: MB-102 administered to participants with impaired renal function (chronic kidney disease (CKD) Stage 3-5), and fluorescence measured by the Brilliance ORFM device. Validation of the Brilliance sensor was conducted. Approximately half of the participants were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. arm 10: MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device (1-2 sensors). The optimized algorithm and final device design of the Brilliance device was tested. Approximately half of the participants were to 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 received two doses of MB-102, 12 hours apart. arm 11: MB-102 administered to participants with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device (1-2 sensors and 2-part sensor). The optimized algorithm and final device design of the Brilliance device was tested. Approximately half of the participants were to 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 received two doses of MB-102, 12 hours apart. arm 12: Two doses of MB-102 administered to participants 12 hours apart, with normal to chronic kidney disease (CKD) Stage 2 renal function, and fluorescence measured by the Brilliance ORFM device (1-2 sensors and 2-part sensor). The optimized algorithm and final device design of the Brilliance device was tested. Approximately half of the participants were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type. arm 13: 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 was tested. Approximately half of the participants were to be enrolled with Fitzpatrick Scale Type I, II or III, and half with Type IV, V and VI skin color type.
Interventions: intervention 1: MB-102-- single dose of 4 µmol/kg intervention 2: MB-102-- single dose of 130 mg intervention 3: MB-102-single dose of 130 mg or 2 doses of 130 mg 12 hours apart intervention 4: MB-102-- two doses of 130 mg 24 hours apart intervention 5: Iohexol intervention 6: QuantumLeap intervention 7: Radiance intervention 8: Brilliance (1 or 2 sensors) intervention 9: Brilliance (2-part sensor)
Intervention descriptions: intervention 1: 4 µmol/kg administered by intravenous injection over 30 seconds, followed by a 10 mL normal saline flush administered intravenously over 30 seconds. intervention 2: 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. intervention 3: 130 mg administered by intravenous injection over 30 seconds, followed by a 10 mL normal saline flush administered intravenously over 30 seconds. intervention 4: 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 5: 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 6: Optical Renal Function Monitor (ORFM) intervention 7: Optical Renal Function Monitor (ORFM) intervention 8: Optical Renal Function Monitor (ORFM) intervention 9: Optical Renal Function Monitor (ORFM)

Protocol documents:
Prot_SAP_000.pdf: 
MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 1 of 103 
CLINICAL STUDY PROTOCOL 
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 
ClinicalTrials.gov NCT02772276
Statement of Compliance 
The study will be conducted in compliance with the protocol, International Conference on Harmonization Good 
Clinical Practice E6 (ICH-GCP), and the applicable regulatory requirements including: The Code of Federal 
Regulations Title 21 CFR Parts 812, 11, 50, 54 and 56 and ISO 14155: 2011(E) Clinical Investigation of Medical 
Devices for Human Subjects – Good Clinical Practice  
Protocol Number: 
ORFM Pilot 2 
Investigational Product: 
MB-102 / Optical Renal Function Monitor (ORFM) 
Prototypes: QuantumLeap, Radiance, and Brilliance 
Phase: 
Pilot (2) 
Sponsor: 
MediBeacon Inc. 
1100 Corporate Square Drive 
St. Louis, MO 63132 
USA 
Date of Protocol: 
18 June 2021 
Version of Protocol: 
13.0 (Amendment 12) 
CONFIDENTIAL 
This protocol may not be reproduced or communicated to a third party without the 
written permission of MediBeacon Inc. 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 2 of 103 
1 
Synopsis 
Protocol Number: 
ORFM Pilot 2 
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 
Investigational 
Product: 
MB-102 
ORFM Prototypes QuantumLeap, Radiance and Brilliance 
Since the initiation of this protocol, the name of the investigational device has been 
changed to the Transdermal GFR Measurement System (TGFR) which consists of MB-
102, the system monitor, and the prototype sensors QuantumLeap, Radiance and 
Brilliance. Supporting documentation may refer to ORFM or TGFR. Both names refer to 
the same investigational device. 
Number of Study 
Sites: 
This study will take place at up to 4 investigational sites in the US. 
Phase: 
Pilot 2 
Objectives: 
•
To evaluate the safety and tolerability of single dose and multiple doses of
MB-102 in subjects with normal and impaired kidney function
•
To determine plasma pharmacokinetics of MB-102 compared to the
pharmacokinetics of iohexol in subjects with normal and impaired renal
function
•
To show that the MB-102 transdermal fluorescence measured GFR using the
ORFM Brilliance device aligns with the measured MB-102 plasma GFR
(Group 3)
•
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 subjects with a
range of skin color types
•
To determine the optimum dose of MB-102 for non-invasive measurement
Study Design: 
Pilot, non-randomized, stratified open-label study. 
Number of Treated 
Subjects:  
Up to 261 subjects are intended to be enrolled across 3 Groups stratified by 
cohorts:  
Group 1: Approximately 60 subjects will be enrolled: Cohort 1: 30 subjects with 
normal to CKD Stage 2 renal function; and Cohort 2: 30 subjects with impaired 
renal function [CKD stage 3 – 4]). Fluorescence will be measured by the 
QuantumLeap ORFM Device.  
Group 2: Up to 60 subjects will be enrolled: Cohort 3: 20 subjects with normal to 
CKD Stage 2 renal function, Cohort 4: 40 subjects with impaired renal function 
[CKD stage 3-5]. Fluorescence will be measured by the Radiance ORFM Device.  
Approximately 10 subjects from Cohort 4 will undergo extended PK collection 
(out to 48 hours). 
Group 1 and Group 2 have been Completed 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 3 of 103 
Group 3:  Up to 141 subjects will be enrolled: 
•
Cohort 5: 8 subjects with normal to CKD stage 2 renal function,
•
Cohort 6: 8 subjects with impaired renal function [CKD stage 3-5].
Fluorescence will be measured by the Brilliance ORFM Device and algorithm
optimization will be performed.
Sensor Optimization Group (SOG) 
In order to further optimize the sensor device, a Sensor Optimization Group 
(SOG) will be enrolled and consist of 18 healthy subjects with normal to CKD 
stage 2 renal function.  An additional group of 9 healthy subjects may be enrolled 
into the SOG.  Therefore, this cohort of subjects may range from a minimum of 9 
subjects up to 27 subjects. SOG subjects will be followed for 12 hours.  
Sensor Verification Group (SeVG) 
A Sensor Verification Group (SeVG) will consist of up to 50 subjects to validate 
the Brilliance sensor.  Sites will enroll subjects with normal renal function to 
Stage 5 CKD. Subjects with normal to stage 2 CKD will be considered the 
“SeVG-1” group and subject to specific eligibility. Subjects who have impaired 
renal function (CKD Stage 3-5) will be considered the “SeVG-2” group and 
subject to specific eligibility requirements.  
A subset of subjects (up to 20) who weigh greater than 110 lbs (50 kg) will 
receive a fixed dose of 7 mL (130 mg).  
A study interim analysis will be performed after completion of the SeVG cohort 
of all previously collected subject data (Groups 1, 2 and 3 through the SevG 
enrollment). This analysis will be performed to summarize clinical data in support 
of pivotal trial regulatory discussions. It is not the intention to stop the study early 
or revamp sample size for the remaining cohorts.  
Cohorts 7 and 8 
An additional 48 subjects may be enrolled to test the optimized algorithm and 
final device design:   
Cohort 7: up to 24 subjects with normal to CKD stage 2 renal function. A subset 
of Cohort 7 subjects will have 2 doses of MB-102 and will be followed for 24 
hours.  Single dosed cohort 7 subjects will be followed for 12 hours.  
Sites enrolling subjects into Cohort 7 (multiple dose group only for Protocol 
Version 11.0,  12.0 and 13.0) should strive to recruit subjects with a baseline 
eGFR > 90 ml/min/1.73m2 if feasible. The intent to enroll more normal subjects is 
to ensure clearance of MB-102 prior to the second dose in order to establish re-
dose timelines for future subjects. In addition, subjects enrolled into the subsets of 
cohort 7 and 8 (Protocol Version 12.0) should strive to enroll subjects at the 
extremes of the Fitzpatrick Skin Scale (I and II and V and VI). Finally, subjects 
enrolled into Cohort 7A and 7B will an eGFR between 90 and 120 ml/min/1.73m2. 
In addition, subjects in Cohort 7B will have a 24 hour period between doses (for a 
total post dose follow-up period of 36 + hours).  
Cohort 8: up to 24 subjects with impaired renal function [CKD stage 3-5] will be 
followed for 48 hours.  
Cohorts 7 and 8 will each enroll a set of subjects first to test the algorithm and 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 4 of 103 
then may be repeated if additional testing is determined to be required. 
A subset of subjects in Cohort 7 and 8 (Cohorts 7A, 8A and 8B) will have a 
second sensor type placed on the pectoralis or sternum. This sensor (the 2-Part 
Brilliance Sensor) is being tested to evaluate a removable adhesive ring that 
would allow future re-use of the sensor portion.  
Treatment: 
Eligible subjects will receive a single dose of MB-102 followed by a single dose 
of iohexol (Groups 1 and 2). Group 3, Cohorts 5, 6, SOG, SeVG-1, SeVG-2 and 
Cohort 8 will only receive a single dose of MB-102 and will not receive iohexol. 
A subset of subjects in Group 3, Cohort 7 will receive 2 doses of MB-102. Blood 
draws will be taken at pre-defined timepoints and the Optical Renal Function 
Monitor (ORFM) fluorescent measurements will be collected over an 8 - 12 hour 
period or up to 24-48 hours in certain cohorts.   
Group 1, Cohort 1 subjects may receive a range of doses of MB-102. Assessments 
of coefficient of variation will determine dose optimization. Remaining Group 1 
subjects and Group 2 subjects will receive the optimized dose.   
Group 3 subjects (cohorts 5, 6, SOG and over half the subjects in the SeVG 
cohort will receive a single dose of 4 µmol/kg. A subset of the SeVG cohort 
(approximately 20 subjects who weigh greater than 110 lbs (50 kg) will receive a 
fixed dose of 7 mL (130 mg) MB-102.  
Cohorts 7 and 8 (regardless of weight) will all receive a fixed dose of 130 mg (7 
mL).  
A subset of Group 3 subjects in Cohort 7 will receive 2 doses of MB-102 (fixed 
dose of 7 mL (130 mg). The 2nd dose will be administered 12 hours after the first 
dose.   For Cohort 7B, subjects will receive their 2nd dose 24 hours after the first 
dose.  
Sensor placement in all subjects from Groups 1 and 2 will be in two different 
locations.  All Group 1 and 2 subjects will have a single sensor placed on the 
sternum.  A second location will be assigned to determine additional sites for 
fluorescent measurements. Group 3 subjects may have 2-3 different sensors 
located on different parts of the body. At least one sensor will be on the sternum 
or pectoralis major.  
•
Group 1 subjects will have fluorescent measurements performed by the
Prototype QuantumLeap device.
•
Group 2 subjects will have fluorescent measurements performed by the
Prototype Radiance device.
•
Group 3 subjects will have fluorescent measurements performed by the
Prototype Brilliance device.
o
A subset of subjects in Group 3 will also have a 2-part Brilliance
sensor placed (cohort 7A, 7B, 8A and 8B)
Study Duration per 
Subject: 
Screening period: up to 40 days prior to dosing; dosing day, and a follow-up visit 
within 7+/-3 days of dosing.   
Study Population: 
Main Criteria for Inclusion (Group 1 and Group 2): 
•
Age > 22 years – male or female


MediBeacon Inc. 
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Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 5 of 103 
o
Eligible female non-pregnant subjects who are either not of child-
bearing potential or willing to use adequate contraception during
the trial
o
Males must be willing to practice abstinence or utilize adequate
contraception from dosing day to at least 7 days post dose
•
Subjects willing to comply with study requirements
•
Subjects 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
Main Criteria for Inclusion (Group 3) 
•
Age > 18 years – male or female
o
Eligible female non-pregnant subjects who are either not of child-
bearing potential or willing to use adequate contraception during
the trial
o
Males must be willing to practice abstinence or utilize adequate
contraception from dosing day to at least 7 days post dose
•
Subjects willing to comply with study requirements
•
Subjects 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
Group 1 Cohort 1; Group 2 Cohort 3; and Group 3 Cohort 5, SOG, SeVG-1 
Cohort and Cohort 7 
•
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
subject’s participation or safety, conduct of the study or interfere with
study assessments
•
Have eGFR (CKD-EPI equation) of ≥60 ml/min/1.73m2 (normal to Stage 2 
CKD) at the time of screening
Approximately half of the patients enrolled in each cohort to have Fitzpatrick 
Scale Type I, II or III skin color type. 
Approximately half of the patients enrolled in each cohort to have Fitzpatrick 
Type IV, V or VI skin color type. 
 Group 1 Cohort 2 
•
Possess stable renal function in the opinion of the PI
•
Have eGFR (CKD-EPI equation) of 15 – 59 mL/min/1.73m2 at the time of
screening
•
Stable use of immunosuppressant medications (when applicable)
~15 subjects per cohort to have Fitzpatrick Type I, II or III skin color type 
~15 subjects per cohort to have Fitzpatrick Type IV, V or VI skin color type 
 Group 2 Cohort 4, and Group 3 Cohorts 6, SeVG-2, and 8 


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Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 6 of 103 
•
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/1.73m2 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 subjects in each cohort to have Fitzpatrick Type I, II 
or III skin color type 
Approximately half of the subjects in each cohort enrolled to have Fitzpatrick 
Type IV, V or VI skin color type 
Main Criteria for Exclusion (Group 1) 
•
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


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 7 of 103 
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 scaring, tattoos or alterations in pigmentation on the sternum
that would alter sensor readings versus other areas of the skin
Additional Exclusion: Group 1 Cohort 1 
•
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: Group 1 Cohort 2 
•
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: (Group 2) 
•
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


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MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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•
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 scaring, tattoos or alterations in pigmentation on the sternum
that would alter sensor readings versus other areas of the skin
Main Criteria for Exclusion: (Group 3) 
•
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 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
•
Significant scaring, tattoos or alterations in pigmentation on the sternum
that would alter sensor readings versus other areas of the skin
Additional Exclusion: Group 2 Cohort 3, and Group 3 Cohorts 5, SOG, SeVG-
1 and Cohort 7 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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•
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: Group 2 Cohort, 4 and Group 3 Cohorts 6, SeVG-2, and 
8 
•
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 Endpoint: 
• Determine plasma pharmacokinetics of MB-102 compared to the
pharmacokinetics of iohexol in subjects with normal and impaired renal
function and a range of skin color types (Groups 1 and 2)
• To show that the MB-102 transdermal fluorescence measured GFR using the
ORFM Brilliance device matches the measured MB-102 plasma GFR (Group
3)
Secondary 
Endpoints: 
• Evaluate the safety and tolerance of MB-102
• Evaluate the safety of the ORFM devices for the noninvasive transdermal
fluorescent detection of MB-102
• Evaluate the effectiveness of the ORFM devices (QuantumLeap, Radiance and
Brilliance) through the comparison of fluorescent measurements versus MB-
102 across the three groups of subjects
• Determine the optimum dose of MB-102 for noninvasive measurement
Primary Safety 
Endpoint: 
• Adverse events (AEs and serious AEs [SAEs], UADEs)
Statistical Methods 
and Sample Size 
Calculations 
As this is a Pilot Study, no formal calculation of sample size was conducted. 
Safety will be evaluated as the incidence of AEs and SAEs/UADEs. These will be 
summarized by cohort and overall. 
Time Schedule: 
Planned Start of Study:  April 2016 
Planned End of Study:   Sep 2021 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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Table of Contents 
1 
Synopsis ..................................................................................................................................... 2 
2 
List of Abbreviations and Definition of Terms ........................................................... 13 
3 
Introduction ........................................................................................................................... 15 
3.1 
Background ..................................................................................................................... 15 
3.2 
Nonclinical Data ............................................................................................................ 16 
3.3 
Clinical Data .................................................................................................................... 23 
3.4 
Study Rationale ............................................................................................................. 24 
4 
Study Objectives .................................................................................................................... 24 
5 
Investigational Plan ............................................................................................................. 25 
5.1 
Overall Study Design and Plan ................................................................................. 25 
5.2 
Dose Optimization ........................................................................................................ 26 
5.2.1 
Group 2 Dosing .................................................................................................................. 28 
5.2.2 
Group 3 Dosing .................................................................................................................. 28 
5.3 
Overview of Study Procedures ................................................................................. 28 
5.3.1 
Groups 1 and 2 ................................................................................................................... 28 
5.3.2 
Group 3 ................................................................................................................................. 29 
5.4 
Discussion of Study Design ........................................................................................ 30 
5.5 
Selection of Study Population ................................................................................... 30 
5.5.1 
Number of Planned Subjects ........................................................................................ 30 
5.5.2 
Inclusion Criteria .............................................................................................................. 30 
5.5.3 
Main Criteria for Exclusion (Group 1): ..................................................................... 31 
5.5.4 
Main Criteria for Exclusion: (Group 2) ..................................................................... 33 
5.5.5 
Main Criteria for Exclusion: (Group 3) ..................................................................... 33 
5.5.6 
Removal of Subjects from Therapy or Assessments ........................................... 35 
5.5.7 
Replacement of Subjects ................................................................................................ 35 
5.6 
Investigational Device ................................................................................................. 35 
5.6.1 
Identity of Investigational Device .............................................................................. 37 
5.6.2 
Labeling ................................................................................................................................ 37 
5.6.3 
Storage, Supply and Return/Destruction ................................................................ 37 
5.6.4 
Device Accountability ..................................................................................................... 37 
5.7 
Investigational Drug .................................................................................................... 37 
5.7.1 
Identity of Investigational Drug .................................................................................. 38 
5.7.2 
Investigational Drug Labeling ...................................................................................... 38 
5.7.3 
Investigational Drug Storage, Supply, Return/Destruction ............................. 39 
5.7.4 
Investigational Drug Accountability .......................................................................... 39 
5.8 
Reference Drug .............................................................................................................. 39 
5.9 
Contact Procedures for Medical Issues Requiring Immediate Attention . 40 
5.10 
Prior and Concomitant Therapy .......................................................................... 40 
5.10.1 
Prohibited Concomitant Medications ....................................................................... 40 
5.10.2 
Stable Use of Immunosuppressive Medications ................................................... 40 


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MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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6 
Study Procedures .................................................................................................................. 41 
6.1 
Schedule of Assessments and Procedures ........................................................... 41 
6.2 
Screening ......................................................................................................................... 51 
6.3 
Dosing Day: Baseline Assessments ......................................................................... 51 
6.4 
MB-102 Dosing (All Groups) ..................................................................................... 53 
6.5 
Iohexol Dosing (Groups 1 and 2 only) ................................................................... 54 
6.6 
Post-dose Study Procedures ..................................................................................... 54 
6.7 
Follow-up Visit ............................................................................................................... 54 
6.8 
Early Withdrawal / Unscheduled Visits ................................................................ 55 
7 
Efficacy and Safety Variables ............................................................................................ 55 
7.1 
Efficacy and Safety Measurements Assessed and Flow Chart ....................... 55 
7.1.1 
Efficacy Assessments ....................................................................................................... 55 
7.1.2 
Safety Assessments .......................................................................................................... 55 
8 
Information for the Investigator: Potential Risks of the Device .......................... 62 
8.1 
Investigational Drug .................................................................................................... 62 
8.2 
ORFM Device ................................................................................................................... 63 
8.2.1 
Adhesive Clip ...................................................................................................................... 64 
8.2.2 
2-Part Brilliance Sensor ................................................................................................. 64 
8.3 
Reference Standard...................................................................................................... 64 
8.4 
Trial Procedures ........................................................................................................... 64 
9 
Statistical Methods ............................................................................................................... 65 
9.1 
Statistical and Analytical Plans ................................................................................ 65 
9.1.1 
Datasets or Populations Analyzed ............................................................................. 65 
9.1.2 
Subject Disposition .......................................................................................................... 65 
9.1.3 
Pharmacokinetic Assessments .................................................................................... 65 
9.1.4 
Safety Variables ................................................................................................................. 69 
9.1.5 
Study Interim Analysis ................................................................................................... 70 
9.1.6 
Early Termination of the Study ................................................................................... 70 
9.1.7 
Determination of Sample Size ...................................................................................... 70 
9.1.8 
Missing Data........................................................................................................................ 70 
10 
Quality Assurance and Quality Control ..................................................................... 71 
10.1 
Training ........................................................................................................................ 71 
10.2 
Audit and Inspection ............................................................................................... 71 
10.3 
Monitoring................................................................................................................... 71 
10.4 
Data Management and Coding.............................................................................. 71 
10.5 
Protocol Deviations .................................................................................................. 72 
10.6 
Device Accountability .............................................................................................. 72 
10.7 
Direct Data Collection ............................................................................................. 73 
11 
Records / Retention ......................................................................................................... 73 
12 
Ethics ..................................................................................................................................... 74 
12.1 
Independent Ethics Committee (IEC) ................................................................ 74 
12.2 
Ethical Conduct of the Study ................................................................................. 74 


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MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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12.3 
Subject Information and Consent........................................................................ 75 
12.4 
Financing and Insurance ........................................................................................ 75 
12.5 
Subject Confidentiality ............................................................................................ 75 
12.6 
Reporting and Publication, Including Archiving ........................................... 76 
13 
Post-Dose Procedures by Group and Cohort ........................................................... 77 
13.1 
Group 1 (Cohorts 1 and 2) and Group 2 (Cohorts 3 and 4 subset) .......... 77 
13.2 
Post-Dose Procedures: Group 2 (Cohort 4 Extended PK Subgroup only)
79 
13.3 
Post-Dose Procedures: Group 3: Cohort 5 ....................................................... 82 
13.4 
Post-Dose Procedures: Group 3: SOG ................................................................. 84 
13.5 
Post-Dose Procedures: Group 3: SeVG, Cohort 6 and 7, 7A: Single Dose 
Subgroup ...................................................................................................................................... 86 
13.6 
Post-Dose Procedures: Group 3: Cohort 7,  7A and 7B: Multiple Dose 
Subgroup ...................................................................................................................................... 88 
13.6.1 
Post First MB-102 Dose Procedures (Cohort 7 and 7A) .................................... 88 
13.6.2 
MB-102 Second Dose Administration (Cohort 7 and 7A) ................................. 89 
13.6.3 
Post First MB-102 Dose Procedures (Cohort 7B) ................................................ 91 
13.6.4 
MB-102 Second Dose Administration (Cohort 7B) ............................................. 93 
13.7 
Post-Dose Procedures: Group 3: Cohort 8 and 8A ......................................... 95 
13.8 
Post-Dose Procedures: Group 3: Cohort 8B ..................................................... 97 
14 
References ........................................................................................................................ 100 
Appendix A Fitzpatrick Scale ................................................................................................. 101 
Appendix B: Package Insert for Omnipaque™ 300 ....................................................... 102 
Investigator Signature Page ................................................................................................... 103 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
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2 
List of Abbreviations and Definition of Terms 
AE 
Adverse event 
AIDS 
Acquired immunodeficiency syndrome 
AKI 
Acute kidney injury 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
AST 
Aspartate aminotransferase 
BMI 
Body Mass Index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
CFR 
Code of Federal Regulations 
CKD 
Chronic kidney disease 
CKD-EPI 
Chronic kidney disease – epidemiology collaboration 
CO2 
Carbon dioxide 
CRF 
Case report form 
Cl 
Chloride 
Cr 
Creatinine 
CrCl 
Creatinine clearance 
CV 
Coefficient of variation 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
FDA 
FS 
Food and Drug Administration 
Fitzpatrick Scale 
GCP 
GFR 
Good Clinical Practice 
Glomerular Filtration Rate 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HCG 
Human chorionic gonadotropin 
HCT 
Hematocrit 
HDL 
High density lipoprotein 
HEENT 
Head, Ears, Eyes, Neck, Throat 
HIV 
Human immunodeficiency virus 
I 
Iodine 
IB 
Investigators Brochure 
ICF 
informed consent form 
ICH 
International Council on Harmonisation 
ICU 
Intensive Care Unit 
IDE 
Investigational Device Exemption 
IEC 
Independent Ethics Committee 
INR 
International normalized ratio 
IP 
Investigational Product 
ISO 
IV 
International Organization for Standardization 
Intravenous 
K 
Potassium 
K2EDTA 
Potassium ethylenediaminetetraacetic acid 
LDL 
Low density lipoprotein 
MedDRA 
Medical Dictionary for Regulatory Activities 
NIH 
National Institute of Health 
NSAID 
Non-steroidal anti-inflammatory drug 
OM 
Operational Manual 
ORFM 
Optical Renal Function Monitor 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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OTC 
Over the counter 
PA 
Physical Assessment (limited) 
PE 
Physical exam (full) 
PI 
Principal Investigator  
PK 
pharmacokinetic 
POC 
Point of care 
PP 
Per Protocol 
RBC 
Red blood cell 
SAE 
Serious Adverse Event 
SAF 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
SCr 
Serum creatinine 
SeVG 
Sensor Verification Group 
SOG 
Sensor Optimization Group 
SNR 
Signal to Noise Ratio 
TGFR 
MediBeacon Transdermal Glomerular Filtration Measurement System 
tGFR 
Transdermal Glomerular Filtration Rate 
Tc-DTPA 
Technetium diethylene triamine - pentaacetate 
TEAE 
treatment-emergent adverse event  
UADE 
Unanticipated Adverse Device Effect 
Vd 
Volume of Distribution 
WBC 
White blood cell 
WHO 
World Health Organization 
WOCBP 
Women of Child-Bearing Potential 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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3 
Introduction 
3.1 
Background 
Therapeutic interventions for acute kidney injury (AKI) patients are delayed due to current 
clinical practice of reliance on a serum creatinine blood test (SCr) for an estimation of 
glomerular filtration rate (GFR). Typically, 24-72 hours elapse from onset of a kidney injury 
event to a SCr indicating a non-normal level (Stevens et al, 2006). Since AKI affects 
upwards of 20% of hospitalized patients and 70% of critically ill patients in the intensive care 
unit (ICU), this contributes to high mortality rates (approaching 60% for those requiring renal 
replacement therapy [Endre at al., 2011]), development of chronic kidney disease (affecting 
an estimated 27 million Americans, accounting for ~ 24% of Medicare costs [NIH 2008]), 
and consequent progression to end stage renal disease (with an estimated 400,000 Americans 
on dialysis [Kidney Disease Statistics for the US]). 
Glomerular filtration rate (GFR) is widely accepted as the best indicator of kidney function 
and is a key component of the diagnosis and management of renal impairment. A simple, 
accurate, and point-of-care (POC) method for determining GFR is needed, as current 
methods for determining GFR are either: 1) practical but lack accuracy, or 2) accurate but 
prohibitively complex, especially for frequent and recurrent measurements. 
Current medical practice for general renal function assessment relies on estimated GFR 
(eGFR).  This involves estimation using equations based on a single serum creatinine 
(SCr) measurement, or a measurement of creatinine clearance (CrCl) based on a 24-hour 
collection of urine plus measurement of a single SCr concentration.  Although readily 
available and convenient, measurement of SCr as an indicator of renal function is 
problematic because it is a lagging indicator of current renal function, lacks sensitivity, and 
may be misleading because it is affected by age, state of hydration, renal perfusion, muscle 
mass, dietary intake, and many other anthropometric and clinical variables (Agarwal, 2003 
and Verhave et al., 2005).  CrCl estimation using timed urine collections can be more 
accurate, but problems with completeness of 24-hour urine collection often result in under 
or over estimation of CrCl. 
Measuring GFR using urinary or plasma clearance of exogenous filtration markers is the 
accepted standard for evaluation of kidney function.  In the past three decades, renally 
filtered exogenous agents such as inulin, iohexol, 125Iodine-iothalamate (125I-iothalamate), 
and technetium-99m-diethylene triamine - pentaacetate (99mTc-DTPA) have all been used to 
determine GFR (Stevens et al., 2006).  From both a safety and effectiveness standpoint, these 
agents are acceptable, although they contain iodine, which can cause anaphylactoid reactions, 
and they can be nephrotoxic when very high volumes are used.  However, they are not used 
routinely to determine GFR because the protocols are time-consuming, complex, and 
expensive, which make their repeated use impractical in many clinical settings, and they may 
require imaging equipment and administration of radioactive agents (Stevens and Levey, 
2009).  Accurate measurement of GFR at the patient’s bedside is highly desirable in order to 
assess the patient’s renal function.  There is a significant need to develop a simple, accurate, 
and POC method for measuring GFR (Erley et al., 2001). 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 16 of 103 
To address this unmet clinical need, MediBeacon is developing a combination product that 
requires the administration of a fluorescent tracer agent designated MB-102 (formerly known 
as MP-3180) that will be detected transdermally by a sensor which is attached to a device 
console.   
MB-102 has been engineered to be excreted from the body by the renal system, and 
specifically by the GFR mechanism. Normal functioning kidneys will remove this agent from 
the body with an approximate 2 hour half-life. Impaired functioning kidneys will take longer 
to excrete the agent and hence result in a longer half-life. An algorithm will be developed 
from the Group 1 data to convert the half-life data to GFR. Group 2 will test the algorithm 
for efficacy and robustness, as well as add to the algorithm database. Group 3 will focus on 
sensor optimization and provide data on the final iteration of the device.  
The sensor contains the light source for excitation of the tracer agent and has a peak 
wavelength of 440 nm. The detector is able to acquire the emission of the tracer agent, which 
has a peak wavelength of 560 nm. The sensor used for QuantumLeap contains the processing 
electronics within the sensor itself, making it a desktop mouse sized device that is then 
connected to the console.  The sensor for the Brilliance device is significantly smaller and 
limited to the materials necessary for excitation and acquisition, and collection and 
processing of the data is conducted within the console.   
The device console is a laptop computer for the QuantumLeap device.  The Radiance device 
will have a similar format but will possess updated software and processing algorithms based 
on Group 1 data analysis.  The Brilliance device will be a tablet console and represents the 
prototype developed for the market.      
This clinical trial will utilize a commonly available x-ray contrast agent, iohexol (5 mL 
administration of Omnipaque™ 300) as a GFR comparator in Groups 1 and 2.  
A subset of subjects in Group 3 (Cohorts 7A, 8A, and 8B) will have a second sensor type 
placed.  This sensor is a two-part design where the adhesive ring is removable (and 
discardable) from the sensor itself.  
Since the initiation of this protocol, the name of the investigational device has been changed 
to the Transdermal GFR Measurement System (TGFR) which consists of MB-102, the 
system monitor, and the prototype sensors QuantumLeap, Radiance and Brilliance. 
Supporting documentation may refer to ORFM or Transdermal GFR Measurement System 
(TGFR). Both names refer to the same investigational device. 
3.2 
Nonclinical Data 
Available nonclinical study data on MB-102 support that the chemistry of the drug 
substance/drug product, and the manufacturing of the drug substance/drug product does not 
present a risk to human subjects.  Table 1 summarizes the nonclinical safety studies 
conducted to date.














MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 23 of 103 
For more detailed information on each of the nonclinical studies, please see the Investigator’s 
Brochure.  
3.3 
Clinical Data 
A total of 234 subjects have been treated with an IV administration of MB-102 across the three 
pilot studies (Pilot 1A, Pilot 1B and Pilot 2 Groups 1, 2 and 3. The Pilot 1 studies enrolled 
subjects with an eGFR indicating normal renal function. The Pilot 2 study enrolled subjects with 
normal renal function and those with renal function in the CKD stage 1-5 range. In addition, a 
total of 11 subjects (6 healthy volunteers and 5 Crohn’s patients) have received a 4 or 8 µmol/kg 
oral dose of MB-102 in a study evaluating the use of MB-102 in the evaluation of gut 
permeability (MediBeacon Protocol 300-01). The total population exposure to MB-102 as of this 
IB version is 245 subjects. A total of 43 subjects (17.6% of the total population across 4 studies) 
were reported to have adverse events (AE). All reported events were mild or moderate in 
severity. No severe events have been reported, nor have any serious adverse events been 
reported. 
There have been no clinically significant findings with regard to vital signs, physical exams or 
ECGs. Overall MB-102 dosed at 4 µmol/kg followed by a 5 mL dose of iohexol (Omnipaque™ 
300) was well tolerated and safe in this population.  Adverse events related to the device itself
were due to the adhesive materials used to hold the ORFM (Optical Renal Function Monitor)
sensor in place.  All device related events were considered mild or moderate in severity. For
more information, please see the Investigator’s Brochure.
MB-102 equilibrates between the vasculature and tissues post intravenous (IV) administration. 
The plasma pharmacokinetics show a peak concentration at the first sample time point. In Pilot 
1A, the first sample time point taken was approximately 5 minutes post administration; in Pilot 
1B the first sample time point taken was approximately 30 minutes post administration. The 
fluorescence pharmacokinetics, reflecting the agent concentration in the tissue, has a peak 
fluorescence intensity in the range of 30 - 90 minutes, depending on the subject.  MB-102 
concentration equilibration between the vasculature and the tissue occurs approximately in this 
same timeframe. 
In the Pilot 2 Groups 1 and 2, the first blood draw was taken at 5 minutes post administration of 
MB-102, and the last at 12 hours post administration. The transdermal fluorescence was 
measured at the sternum and one other location for each subject using the prototype device 
QuantumLeap and Radiance. For all 120 subjects over the wide range of GFR values, the 
following were observed: 
•
A two compartment plasma pharmacokinetic profile
•
A high correlation between the MB-102 and iohexol plasma derived GFR values
•
A high correlation between the MB-102 plasma and transdermal fluorescence
pharmacokinetics


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 24 of 103 
3.4 
Study Rationale 
This clinical study is the first to assess pharmacokinetics (PK) and function of the ORFM device 
in subjects with impaired kidney function. In addition, it will evaluate the impact of different 
skin color types on readouts by the ORFM prototype devices QuantumLeap, Radiance and 
Brilliance. These data will be used to further refine the algorithms used in the ORFM device for 
the pivotal trial and commercial development.  Safety and tolerance of MB-102 will also be 
assessed in a larger population of subjects.  
4 
Study Objectives 
The objectives of this pilot study are: 
•
To evaluate the safety and tolerability of single dose and multiple doses of MB-102 in
subjects with normal and impaired kidney function
•
To determine plasma pharmacokinetics of MB-102 compared to the pharmacokinetics of
iohexol in subjects with normal and impaired renal function (Groups 1 and 2)
•
To show that the MB-102 transdermal fluorescence measured GFR using the ORFM
Brilliance device aligns with the measured MB-102 plasma GFR (Group 3)
•
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 on subjects with a range of skin color types
•
To determine the optimum dose of MB-102 for non-invasive measurement


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 25 of 103 
5 
Investigational Plan 
5.1 
Overall Study Design and Plan 
Protocol ORFM Pilot 2 is a pilot, safety and pharmacokinetic study of MB-102 versus iohexol 
(Groups 1 and 2) and the use of the non-invasive ORFM device in normal and compromised 
renal function subjects with different skin color types.  
Up to 261 subjects are intended to be enrolled across 3 Groups stratified by cohorts: 
Group 1: Approximately 60 subjects will be enrolled: 
•
Cohort 1: 30 subjects with normal to CKD Stage 2 renal function
•
Cohort 2: 30 subjects with impaired renal function (CKD stage 3-4).
Fluorescence will be measured by the QuantumLeap ORFM Device. 
Data from Group 1 subjects will be used to determine dose optimization. In addition, Group 1 
data will be analysed in order to modify the sensor algorithm for use in Group 2 subjects.   These 
updates will then be implemented prior to initiation of Group 2 enrollment. 
Group 2: Up to 60 subjects will be enrolled: 
•
Cohort 3: 20 subjects with normal to CKD Stage 2 renal function
•
Cohort 4: 40 subjects with impaired renal function (CKD stage 3-5)
o
Approximately 10 subjects in Cohort 4 will have extended PK collections (out to
48 hours)
Fluorescence will be measured by the Radiance ORFM Device. 
Group 3: Up to 141 subjects to be enrolled: 
•
Cohort 5: 8 subjects to have normal to CKD Stage 2 renal function
•
Cohort 6: 8 subjects with impaired renal function (CKD stage 3-5)
•
Sensor Optimization Group (SOG): 18 subjects with normal to CKD Stage 2 renal
function; if optimization still requires additional work; a third and final group of 9
subjects will be enrolled to finalize the device and algorithm design.
•
Sensor Validation Group (SeVG): up to 50 subjects will be enrolled who have normal
renal function to Stage 5 CKD. A subset of subjects (approximately 20) who weigh
greater than 110 lbs (50 kg) will receive a fixed dose of 7 mL (130 mg). Subjects
receiving the fixed dose may be normal or renally compromised.
A study interim analysis will be performed after completion of the SeVG cohort of all 
previously collected subject data (Groups 1, 2 and 3 through the SevG enrollment). This 
analysis will be performed to summarize clinical data in support of pivotal product development 
and regulatory submissions. It is not the intention to stop the study early or revamp sample size 
for the remaining cohorts.  


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 26 of 103 
The final algorithm and sensor will be further tested in up to 48 additional subjects: 
•
Cohort 7: up to 24 subjects to have normal to CKD Stage 2 renal function
o
A subset of cohort 7 subjects will have 2 doses of MB-102; the 2nd dose of MB-
102 will be administered 12 hours after the first dose (original Cohort 7, 7A)
o
A subset of subjects (Cohort 7B) will have 2 doses of MB-102; the 2nd dose of
MB-102 will be administered 24 hours after the first dose
•
Cohort 8: up to 24 subjects with impaired renal function (CKD stage 3-5) and followed
for 24-48 hours
•
All cohort 7 and 8 subjects will receive the fixed dose of 130 mg (7 mL).
Cohorts 7 and 8 will be divided into the following subsets in order to test additional sensor types 
in development.  These subsets are outlined in Table 2.  
Table 2 Cohort 7 and 8 Subsets 
Cohort 
Subgroups 
Dosing 
Follow-up (Hrs) Sensors 
Enrollment 
Cohort 7 
Single or 2 doses 
12 - 24 hours 
Brilliance (1-2 sensors/subject) 
Up to 24 
subjects 
Cohort 7A 
Single or 2 doses 
12 - 24 hours 
Brilliance (1-2 sensors/subject) and 
Brilliance 2-part sensor 
Cohort 7B 
2 doses 
36 hours 
Brilliance (1-2 sensors/subject) and 
Brilliance 2-part sensor 
Cohort 8 
Single dose 
48 hours 
Brilliance (1-2 sensors/subject) 
Up to 16 
subjects 
Cohort 8A 
Single dose 
48 hours 
Brilliance (1-2 sensors/subject) and 
Brilliance 2-part sensor 
Cohort 8B 
Single dose 
24 hours 
Brilliance (1-2 sensors/subject) and 
Brilliance 2-part sensor 
Up to 8 
subjects 
Total cohort 7 and 8 Enrollment: 
Up to 48 
Fluorescence will be measured by the Brilliance ORFM Device and some subjects will be 
exposed to a 2-Part Brilliance sensor.  
All Cohorts will enroll approximately half their subjects with Fitzpatrick Scale (FS) Type I, II or 
III, and half with Type IV, V and VI skin color type (Fitzpatrick, 1975) (Appendix A 
Fitzpatrick Scale).  
5.2 
Dose Optimization 
In order to determine the optimal dose of MB-102, Group 1 subjects may receive different doses 
of Investigational Product (IP).  The maximum dose of 4 µmol/kg has already been tested in 8 
subjects in a prior clinical study (Pilot 1B) and found to be safe and well tolerated.   
Coefficient of Variation (CV) will be used as the criterion for selecting dose.  CV is defined here 
as the standard deviation divided by the mean (expressed as a percentage) of the time constants 
from multiple single exponential fits to the trans-cutaneous fluorescence emission decay over 
non-overlapping 15 minute time windows between 2 and 4 hours after IP dosing.  The CVs will 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 27 of 103 
be separately averaged across 2 subjects within FS I, II and III skin color types and 2 subjects 
within FS IV, V, and VI skin color types.   
The initial dose will be 4 µmol/kg, and the target CV will be 5%.  Dose de-escalation will only 
be performed if the resulting average CVs for both skin type groups are below the maximum 
stated requirements.  As shown in Figure 1, the CV thresholds for dose de-escalation from 4 to 3 
µmol/kg, 3 to 2 µmol/kg, and 2 to 1 µmol/kg are 4.3%, 4.1%, 3.5%, respectively.  These dose 
scaling targets assume that the CV has a square root dependence on the signal size (i.e. "Poisson" 
noise distribution), but after dose de-escalation, a second CV determination will be made to 
ensure the target CV of 5% has been achieved.  Details on the methods and analysis of dose 
selection will be available in a separate MediBeacon Experimental Protocol. 
Figure 1 Dose Optimization Schema 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
Page 28 of 103 
5.2.1 Group 2 Dosing 
Subjects enrolled in Group 2 will receive a dose of 4 µmol/kg of MB-102. No dose optimization 
work will be conducted.  
5.2.2 Group 3 Dosing 
Subjects enrolled in Group 3, Cohorts 5, 6, SOG and part of the SeVG group will receive a dose 
of 4 µmol/kg of MB-102. No dose optimization work will be conducted.  
A subset of SeVG subjects (up to 20 subjects who weigh greater than 110 lbs [50 kg]) and all 
subjects in cohorts 7 and 8 will receive a fixed dose of 7 mL (130 mg).  This dose is equivalent 
to what a 191 lb subject would receive if dosed at the standard 4 µmol/kg dose level. This dose 
change is within the safety margin of previously performed non-clinical studies. The purpose of 
testing a fixed dose level is to determine if such a dose will be adequate across a variety of 
subject weights and still remain an accurate measurement of tGFR. A fixed dose level would 
simplify dose preparation when the product goes to market.  
A subset of subjects enrolled into Cohort 7 will receive 2 doses of MB-102 (both doses will at 
the fixed dose level of 7 mL or 130 mg). The 2nd dose of MB-102 will be administered either 12 
hours or 24 hours (Cohort 7B) after the first dose.   
5.3 
Overview of Study Procedures 
5.3.1 Groups 1 and 2 
Potential subjects will be screened for eligibility within 40 days prior to planned dosing. 
Following pre-dose procedures to ensure eligibility, two ORFM sensors will be affixed to the 
subjects in Groups 1 and 2; one on the sternum (all subjects) and a second one on an alternative 
location which may include the forehead, occipital triangle, pectoralis major, lower hip, upper 
hip, lower sternum or chin.  The subject will then receive MB-102 and iohexol injections.  MB-
102 will be administered by IV injection over 30 seconds, followed by a 10 mL saline flush IV 
over 30 seconds. Iohexol will be administered to each subject following the MB-102 
administration by IV injection over 30 seconds, followed by a 10 mL saline flush IV over 30 
seconds. 
PK sampling will be collected pre-dose and at 5, 10, 15, 30, 60, 90, 120, 180, 240, 300, 360, 480, 
600 and 720 minutes post-dose.  
For the subgroup in Cohort 4 who consent to have extended PK collection, additional PK 
samples will occur at 960 (16 hours), 1440 minutes (24 hours), 1920 minutes (32 hours), 2400 
minutes (40 hours) and 2880 minutes (48 hours) post-dose.  
Urine will be collected pre-dose and for the 12 hour duration of PK sampling (and extended out 
to 48 hours for subjects in the extended PK subgroup) for all subjects in Groups 1 and 2. 
Aliquots of urine will be collected during each void, and the total volume excreted during the 12 
or 48 hour post-dose period will be recorded.  


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Safety assessments in the form of clinical labs, vital signs, ECGs and adverse event collection 
will occur during the dosing day.  
Within 7 +/- 3 days of dosing, subjects will return to the study center for additional safety 
follow-up assessments.  
5.3.2 Group 3 
Potential subjects will be screened for eligibility within 40 days prior to planned dosing. 
Following pre-dose procedures to ensure eligibility, one ORFM sensor will be affixed to the 
subject and (in certain subjects) a 2nd sensor (connected to a separate device) may be attached to 
a 2nd location. Sensor placement locations include: the sternum, the forehead, occipital triangle 
(side of neck), pectoralis major, lower hip, upper hip, lower sternum or chin.  A dose of 4 
µmol/kg MB-102 will be administered by IV injection over 30 seconds, followed by a 10 mL 
saline flush IV over 30 seconds.  
PK sampling in cohort 5 will be collected pre-dose and at 5, 10, 15, 30, 60, 90, 120, 180, 240, 
300, 360, and 480 minutes post-dose (8 hour collection period).  
PK sampling in cohorts 6, 7 (single dose subjects), the SOG cohort, SeVG-1 and SeVG-2 will be 
collected pre-dose and at 5, 10, 15, 30, 60, 90, 120, 180, 240, 300, 360, 480, 600 and 720 
minutes post-dose (12 hour collection period). 
PK sampling in cohort 7 [including 7A and 7B] (multiple dose subjects) will be collected at the 
following timepoints: pre-dose and 5, (±1 min), 120, 180, 240, 300 (±5 min), 360, 480 and 600 
(±10 min).  In addition, a PK sample will be drawn at 720 minutes after the first dose 
administered in Cohort 7B.  Prior to the 2nd dose, a pre-second dose draw will be performed. 
Blood draws will re-start after the administration of the 2nd dose and be collected at the following 
timepoints: 5 (±1 min), 120, 180, 240, 300 (±5 min), 360, 480, and 600 (±10 min). It is 
anticipated that this subset of subjects will remain at the study center for 24 – 36+ hours. As of 
Amendment 11, PK sampling for multiple dose subjects will have an additional PK blood draw 
at 60 minutes (±5 min).  
PK sampling in cohort 8, and 8A will be collected pre-dose and at 5, 10, 15, 30, 60, 90, 120, 180, 
240, 300, 360, 480, 600, 720 minutes (12 hours); 960 (16 hours), 1440 (24 hours), 1920 (32 
hours), 2400 (40 hours) and 2880 minutes (48 hours).  
PK sampling in cohort 8B will be collected at collected pre-dose and at 5, 10, 15, 30, 60, 90, 120, 
180, 240, 300, 360, 480, 600, 720 minutes (12 hours); 960 (16 hours), and 1440 (24 hours). 
Urine will not be collected in Group 3. 
Safety assessments in the form of clinical labs, vital signs, ECGs and adverse event collection 
will occur during the dosing day.  


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Version 13.0 
18 June 2021 
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Prior to sensor placement, and each time a sensor is removed (or a sensor replaced) melanin and 
erythema will be measured using a Mexameter MX18. Photographs of the sensor once affixed 
to a subject may also be taken in order to assess the utility of the adhesive. No subject identifying 
features will be included in the photographs.  
Within 7 +/- 3 days of dosing, subjects will return to the study center for additional safety 
follow-up assessments.  
5.4 
Discussion of Study Design 
This pilot study is designed to provide safety and pharmacokinetic data as well as ORFM data 
that will be used for the design of future studies.  
5.5 
Selection of Study Population 
5.5.1 Number of Planned Subjects 
Up to 261 subjects divided into 3 enrollment Groups with normal or impaired renal function who 
meet all of the eligibility criteria will be enrolled. An effort will be made to ensure both men and 
women are enrolled across all cohorts.  
No sample size calculation was made to determine the number of planned subjects.  This is a 
hypothesis generating study to optimize the device and algorithm and is not intended to meet 
statistical significance for this purpose. 
5.5.2 Inclusion Criteria 
To be eligible for study entry, all subjects must satisfy all of the following criteria: 
Main Criteria for Inclusion (Group 1 and Group 2): 
•
Age > 22 years – male or female
o
Eligible female non-pregnant subjects who are either not of child-bearing
potential or willing to use adequate contraception during the trial
o
Males must be willing to practice abstinence or utilize adequate contraception
from dosing day to at least 7 days post dose
•
Subjects willing to comply with study requirements
•
Subjects 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
Main Criteria for Inclusion (Group 3): 
•
Age > 18 years – male or female
o
Eligible female non-pregnant subjects who are either not of child-bearing
potential or willing to use adequate contraception during the trial
o
Males must be willing to practice abstinence or utilize adequate contraception
from dosing day to at least 7 days post dose


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Version 13.0 
18 June 2021 
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•
Subjects willing to comply with study requirements
•
Subjects 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
Group 1 Cohort 1 (30 subjects), Group 2 Cohort 3 (20 subjects) and Group 3: Cohorts 5 (8 
subjects), SOG Cohort (up to 27 subjects), SeVG-1 (up to 25 subjects) and Cohort 7 (up to 16 
subjects) 
•
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 subject’s participation or safety, conduct of the
study or interfere with study assessments
•
Have eGFR (CKD-EPI equation) of ≥60 ml/min/1.73m2 (normal to Stage 2 CKD) at the
time of screening
Approximately half of the patients enrolled in each cohort will have Fitzpatrick Scale Type I, II 
or III skin color type and the other half will have Fitzpatrick scale Type IV, V or VI skin color 
type. 
  Group 1 Cohort 2 (30 subjects) 
•
Possess stable renal function in the opinion of the PI
•
Have eGFR (CKD-EPI equation) of 15 – 59 mL/min/1.73m2 at the time of screening
•
Stable use of immunosuppressant medications (when applicable)
 ~15 subjects per cohort to have Fitzpatrick Type I, II or III skin color type 
 ~15 subjects per cohort to have Fitzpatrick Type IV, V or VI skin color type 
Group 2 Cohort 4 (40 subjects) and Group 3 Cohorts 6 (8 subjects), SeVG-2 (up to 25 subjects) 
and Cohort 8 (up to 16 subjects) 
•
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/1.73m2 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) (see Section 5.10.2 and Table 3).
Approximately half of the subjects per Cohort to have Fitzpatrick Type I, II or III skin color type 
Approximately half of the subjects per Cohort to have Fitzpatrick Type IV, V or VI skin color 
type. 
5.5.3 Main Criteria for Exclusion (Group 1): 
•
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


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18 June 2021 
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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 scaring, tattoos or alterations in pigmentation on the sternum that would alter
sensor readings versus other areas of the skin
Additional Exclusion: Group 1 Cohort 1: 
•
Any other serious or uncontrolled medical disorder, active infection, physical exam
finding, laboratory finding, altered medical exam or psychiatric condition that in the
opinion of the investigator would limit the subjects’ ability to complete study
requirements or increase risk to the subject or interpretability of the study results.
•
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: Group 1 Cohort 2 
•
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


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Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
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5.5.4 Main Criteria for Exclusion: (Group 2) 
•
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 treatment 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, 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).
•
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
5.5.5 Main Criteria for Exclusion: (Group 3) 
•
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


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Protocol No.  ORFM Pilot 2 
Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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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
•
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 treatment 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, and 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 may be eligible).
•
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
•
Significant scarring, tattoos or alterations in pigmentation on the sternum that would alter
sensor readings versus other areas of the skin
Additional Exclusion: Group 2 Cohort 3 and Group 3 Cohorts 5, SOG Cohort, SeVG-1 and 
Cohort 7 
•
History of significant cardiovascular disease, heart failure, myocardial infarction in the
past 3 months, or NYHA class 3 or 4 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.
Sites enrolling subjects into Cohort 7 (multiple dose group only for Protocol Versions 11.0 and 
12.0) should strive to recruit subjects with a baseline eGFR > 90 ml/min/1.73m2 if feasible. The 
intent to enroll more normal subjects is to ensure clearance of MB-102 prior to the second dose 
in order to establish re-dose timelines for future subjects. In addition, subjects enrolled into the 
subsets of cohort 7 and 8 (Protocol Version 12.0) should strive to enroll subjects at the extremes 
of the Fitzpatrick Skin Scale (I and II and V and VI). Finally, subjects enrolled into Cohort 7A 


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Version 13.0 
18 June 2021 
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and 7B will an eGFR between 90 and 120 ml/min/1.73m2. In addition, subjects in Cohort 7B 
will have a 24 hour period between doses (for a total post dose follow-up period of 36 + hours). 
Additional Exclusion: Group 2 Cohort 4 and Group 3 Cohorts 6, SeVG-2, and 8 
•
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
5.5.6 Removal of Subjects from Therapy or Assessments 
In accordance with applicable regulations, a subject has the right to withdraw from the study at 
any time and for any reason without prejudice to his or her future medical care by the physician 
or at the institution where the subject’s care is provided.   
Reasons for withdrawal from the study may include 1 or more of the following: 
•
Withdrawal of consent
•
Administrative decision by the PI or MediBeacon
•
Adverse event requiring removal from the study
•
Physician prescribes a treatment that would conflict with the subject’s continued
participation in the study
Subjects withdrawing from the study will be encouraged to complete the follow-up study visit 
including all safety evaluations.  The reason(s) for withdrawal will be documented. 
Reasonable efforts will be made to contact subjects who are lost to follow-up.  All attempts and 
contacts must be documented in the subject’s file.   
The sponsor has the right to terminate the study at any time due to a safety issue or if special 
circumstances arise making further treatment of subjects impossible.  In this event, the 
investigator(s) will be informed of the reason for study termination.  
5.5.7 Replacement of Subjects 
Should a subject meet eligibility, but is unable to be dosed, that subject may be replaced.  
Subjects will not be replaced if they are dosed but unable to complete study assessments.   
5.6 
Investigational Device 
The Optical Renal Function Monitor (ORFM) investigational device is intended to measure the 


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Version 13.0 
18 June 2021 
CONFIDENTIAL INFORMATION 
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Glomerular Filtration Rate (GFR) in patients with normal or impaired renal function by 
noninvasively monitoring fluorescent light emission from an exogenous tracer agent (MB-102) 
over time. The devices utilized in this protocol are ORFM Prototypes QuantumLeap, and 
Radiance as next generation from the ORFM prototype 1 used in Pilot 1B. The Brilliance device 
being evaluated in Group 3 will be a prototype of the final device used for the pivotal trial and 
future marketing.  
Subjects in Group 1 will be evaluated using ORFM prototype QuantumLeap, and subjects 
enrolled into Group 2 will be evaluated using ORFM prototype Radiance.  Subjects in Group 3 
will be evaluated using the ORFM prototype Brilliance. The primary difference in the prototypes 
is the sensor—prototype QuantumLeap and Radiance used with Group 1 and 2 subjects will have 
a “mouse” sized probe that incorporates all the electronics into the sensor itself. Prototype 
Brilliance used with Group 3 subjects will have a smaller sized probe where the majority of the 
electronics are found in a tablet connected to the probe. Design change controls and design 
verification according to 21 CFR 820.30 will be fully applied and documented prior to use in the 
study.  
The study device QuantumLeap (used in Group 1) and the Radiance device (used in Group 2) 
will be operated solely by the Sponsor. Both devices will be set-up and run in accordance with 
the applicable ORFM Operator’s Manual (OM). The sponsor will also provide oversight of the 
use of the Brilliance device.  
Site staff will place and affix the ORFM device sensors for all enrolled subjects. For subjects in 
Groups 1 and 2, two separate sensors will be attached via standard adhesive pads to two 
locations on each subject: sternum and one of the following positions: forehead, occipital 
triangle, pectoralis major, upper hip, lower hip, chin, and lower sternum.  If one location is 
determined to not be feasible, it may be eliminated from use with future enrolled subjects.  In 
addition, if another location is deemed feasible for testing, it may be selected for use in future 
study subjects. In Group 3, some subjects may be connected to two Brilliance devices and have a 
sensor on more than one location.  
In Group 3, cohorts 7A, 7B, 8A and 8B, the Brilliance 2-Part Sensor will be placed on subjects in 
addition to the 1-2 standard Brilliance sensors. The additional sensors will be placed on the 
sternum or the pectoralis major. 
The only parts of the investigational device component (ORFM) that come into contact with the 
subject is the single-use adhesive pad attached to the sensors.  This provides a smooth, surface, 
which is affixed to the subject’s skin.  The sensors remain in contact with the skin and are held in 
place by means of a self-adhesive pad, typical of those used for disposable ECG patches. Sensors 
placed on the forehead (for Groups 1 and 2) may require an additional head strap in order to 
maintain the position. The sensors remain affixed to the patient for approximately 9 - 12.5 hours. 
This may be increased in the extended PK group for up to 16 hours, out to 24 hours for the 
Cohort 7 multiple dose group and Cohort 8B, and out to 48 hours for Cohort 4 extended PK 
subjects and Cohort 8 and 8A.  


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Version 13.0 
18 June 2021 
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As of amendment 10 (protocol version 11) dated 18 Nov 2020; subjects will also be exposed to a 
commercially available skin adhesive clip that will attach to the sensor cable. The purpose of this 
clip is to secure the sensor cable to allow for subject movements. It will be tested in cohorts 7 
and 8 only and used in all subset cohorts.    
5.6.1 Identity of Investigational Device 
The ORMF is manufactured by MediBeacon Inc. (St. Louis, MO, USA).  All packaging and 
labeling operations will be performed according to current Good Manufacturing Practice (GMP), 
ISO 13485 and the relevant regulatory requirements. 
5.6.2 Labeling 
Each device will be clearly labelled with a Serial Number. The Brilliance Device will be labelled 
“CAUTION-Investigational device.  Limited by Federal (or United States) law to investigational 
use” Per 21 CFR 812.5(a). 
5.6.3 Storage, Supply and Return/Destruction 
Multiple investigational devices (consoles and sensors in Groups 1 and 2) (which will be re-used 
across study subjects) will be provided to the clinical site. Disposable items (adhesive pads) will 
be single-subject use only. Devices and disposable materials must be stored in a secure location 
and are only for use during the clinical trial. All devices will be returned to the Sponsor at the 
conclusion of the trial. For Group 3, sensors will be single use.  
All parts coming in contact with the subject’s skin are disposable (adhesive pads). 
5.6.4 Device Accountability  
All inventory received for clinical trial use will be tracked. Unused inventory will be returned to 
MediBeacon or disposed of following instructions from the Sponsor. An investigational device 
accountability record will be kept current and will contain:  
•
Subject ID (screening number)
•
Device(s) console serial number used
•
Sensor serial number
•
Date of dosing
•
Any observations noted during the use of the device on a subject
5.7 
Investigational Drug 
MB-102 is a bis-serine aminopyrazine that will be used as an exogenous fluorescent Glomerular 
Filtration Rate (GFR) agent.  This agent is excited by blue light and emits green light.   
MB-102 has the following characteristics: 
•
Produces fluorescence in vivo when excited by blue light, which can be reliably detected


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18 June 2021 
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by transdermal measurement when MB-102 is injected intravenously 
•
Has elimination kinetics that allows determination of GFR from fluorescence
measurement within a clinically useful timeframe
•
Is filtered by the kidney
•
Is not protein bound
•
Is not expected to undergo secretion or tubular reabsorption
•
Is not expected to be metabolized by the liver or other organs
•
Is not expected to affect kidney function
•
Has been shown to be safe in animal models, in therapeutic dose range
•
Is photostable in its administration form and during sample handling and analysis
•
Has been shown to be a reasonable GFR tracer agent in nonclinical animal models
A sixty (60) month stability-testing program conducted under Good Manufacturing Practices 
(GMP) for the Active Pharmaceutical Ingredient (API) Lot # 07-130227-02/02-43-01 used in the 
Pilot 2 studies was completed. Results show negligible change with respect to the zero time 
parameters at 60 months. 
A sixty (60) month stability-testing program conducted under GMP for our latest manufactured 
API Lot # 2337-1706-00256 was initiated. Results show negligible change with respect to the 
zero time parameters at the two year time point.  
A 24 month stability-testing program for the GMP formulated product Batch P03915, which is 
being used for Groups 1 and 2 in this Pilot 2 study, has been completed. Results show negligible 
change with respect to the zero time parameters.  
Formulated product with designation Batch P04517 was manufactured under GMP conditions by 
AMRI using API Lot # 2337-1706-00256. This batch was placed on stability at 2 - 8°C for a 
three year period. At the 24 month time point, there is negligible degradation in purity and 
essentially no change in the total impurity amount. 
5.7.1 Identity of Investigational Drug 
MB-102 is packaged in amber vials at a concentration of 18.6 mg/mL in a 3 mL volume.  MB-
102 in formulation includes the following: sodium dihydrogen phosphate monohydrate, sodium 
hydroxide, sodium chloride, water for injection. Instructions for preparation of MB-102 for 
investigational use will be included in the Study Procedure Manual.  
5.7.2 Investigational Drug Labeling 
MB-102 drug labels include the following information: 
MP-3180 (MB-102) 
18.6 mg/mL solution for injection 
3mL of MP-3180 (MB-102) in formulation 
Product for IV use only 
Lot No: XXXXX 
Mfg Date: XX/XXX/XXXX 


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Version 13.0 
18 June 2021 
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Caution: New Drug-Limited by Federal (or United States) 
law to investigational use. 
Manufactured by: 
AMRI (Glasgow) Limited 
Todd Campus, West of Scotland Science Park 
Acre Road, Glasgow, G20 OXA, UK 
5.7.3 Investigational Drug Storage, Supply, Return/Destruction 
MB-102 vials should be stored at 2°C – 8°C in a secure location. Records of temperature will be 
maintained by the clinical site.  
Adequate supply from manufacturing lots (batch numbers P03915/1 and P04517-1) will be 
provided to the investigational site.  
All study medications will be stored, reconciled and either returned to the sponsor or destroyed 
according to applicable regulations following authorization by MediBeacon or designee. 
5.7.4 Investigational Drug Accountability 
Drug accountability will be maintained by the clinical site and will be reviewed during the study 
and 100% reconciled at the conclusion of the trial.  
Drug accountability documentation may include, but may not be limited to, the following 
information: 
•
Receipt date
•
Lot
•
Expiry and/or manufacture date
•
Dispensing information
5.8 
Reference Drug 
Iohexol (Omnipaque™ 300) is an FDA approved iodinated contrast media used to enhance x-ray 
or CT imaging tests.  It has minimal protein binding and approximately 80-90% is excreted in 
the urine.  
Omnipaque™ is provided as a sterile, pyrogen-free, colorless to pale-yellow solution. The 
concentration used as the reference standard in this trial is 647 mg/mL. Five millilters (5 mL) 
will be administered therefore the total dose received will be 3,235 mg. Note: typical doses 
administered in accordance with the Package Insert for Omnipaque™ 300 for imaging 
procedures range from 50 – 200 mL (32.4 – 129.0 g).   
Each milliliter of iohexol contains 1.21 mg tromethamine and 0.1 mg edetate calcium disodium 
with the pH adjusted between 6.8 and 7.7 with hydrochloric acid or sodium hydroxide.  




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Protocol No.  ORFM Pilot 2 
Version 13.0 
 
18 June 2021 
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6 
Study Procedures 
6.1 
Schedule of Assessments and Procedures 
The schedule of planned study assessments is shown in Table 4 for Groups 1 and 2 and in Table 
5 for Group 3 Cohort 5 only, Table 6 for Group 3: SOG, SeVG-1 and 2, Cohort 6, Cohorts 7 
(Single Dose) and 8; and Table 7 for Cohort 7 (multiple dose subjects).




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Groups 1 and 2 Table Legend 
a. Consent is prior to any study related procedures being conducted. 
b. Negative pregnancy serum human chorionic gonadotropin (hCG) test at screening for women of childbearing potential (WOCBP) is required 
for eligibility and at the follow-up visit. On dosing day, a urine pregnancy test will be conducted for WOCBP  
c. A full physical examination (PE) is required at the screening visit.  A full PE or limited physical assessment (PA) may be conducted prior to 
dosing and (if symptoms direct) within the last 2 hours of PK assessments (Limited PA includes assessments of HEENT, cardiovascular, 
abdominal systems). A full or limited exam may be conducted at the follow-up visit.  
d. Vital signs include blood pressure (BP), respiration rate, heart rate and temperature.   Note: temperature is collected at screening, pre-dose, at 
the conclusion of dosing day (and at the 24 and 48 hour vital sign collection for the extended PK subgroup) and at the follow-up visit (and not 
during multiple timepoints on dosing day). Whenever possible, the subject should be seated and resting for approximately 5 minutes prior to 
all measurements.   Vital signs will be collected at screening, pre-dose and at the following post-dose timepoints: [6, 11, 16 min (±1 min)]; 
[35, 65, 95, 125 min (±5 min)]; [185, 245, 305, 365, 485, 605, 725 min (±10 min)]. The extended PK group will have additional vital signs 
measured at [965 (±10 min)] and [1445, 1925, 2405, 2885 min (±30 min)].  
e. Height and Weight should be measured at screening and weight only verified on dosing day 
f. 
Clinical laboratory assessments will be analyzed by a central laboratory and consist of the measurements noted in Table 8. Coagulation panel will 
be conducted at Screening, pre-dose, and as part of the post-dose draw clinical labs at 720 min. 
g. ORFM data collection will commence prior to dose administration. At least 15 minutes prior to dosing, sensors should be placed on the subject 
and the ORFM device started. Data collection will continue through 12 hours of PK sampling and up to 16 hours in the extended PK group.  
h. MB-102 will be administered via IV bolus injection over a 30 second injection period. This will be followed by a 10 mL saline flush over 30 
seconds. Time of administration will be recorded. Iohexol will be administered after completion of the saline flush following MB-102 
administration. Iohexol should also be injected IV over 30 seconds followed by a 10 mL saline flush over 30 seconds.  
i. 
PK blood draws will be collected at the following timepoints: 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.  Blood draws should be via a venous catheter and will be processed in accordance with 
instructions available in the Study Procedure Manual. Subjects enrolled in the extended PK subgroup will have additional PK sampling at 
[960 (16 hours), 1440 min (24 hours), 1920 min (32 hours) and 2400 (40 hours) 2880 min (48 hours) (±30 min)].  
j. 
Urine collection will occur pre-dose, and whenever urination occurs. The time of collection will be obtained, and a sample collected in 
accordance with the instructions in the Study Procedure Manual. The total volume of urine excreted during the pre-dose through the 12 or 48 
hour extended PK period will be recorded.  
k. A 12 lead electrocardiogram (ECG) will be performed at Screening, Pre-dose, and at the following post-dose time-points: 55 min (± 5 min), 
115 min (± 5 min), 235 min (±5 min) and 740 min (±10 min). In addition, subjects in the extended PK group will have an ECG collected at 
1420 min (±30 min) and 2860 min (±30 min). Subjects should be resting quietly for 10-15 minutes prior to the ECG collection. 
l. 
Subjects will be required to consume 240 mL of ambient temperature water approximately 1 hour prior to dosing and again at approximately 
30 minutes prior to dosing. Following dosing, water consumption will be permitted ab libitum. A standard meal will be provided as a 
breakfast, lunch and dinner at appropriate times during the dosing day. Snacks and juice drinks may also be provided.  
m. Concomitant medications administered within 7 days prior to baseline through the final follow-up visit will be recorded.   
n. Adverse events are collected from the time of dosing through the follow-up visit. 




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Group 3 Cohort 5 Table Legend 
a. Consent is prior to any study related procedures being conducted. 
b. Negative pregnancy serum human chorionic gonadotropin (hCG) test at screening for women of childbearing potential (WOCBP) is required 
for eligibility and at the follow-up visit. On dosing day, a urine pregnancy test will be conducted for WOCBP  
c. A full physical examination (PE) is required at the screening visit.  A full PE or limited physical assessment (PA) may be conducted prior to 
dosing and (if symptoms direct) within the last 2 hours of PK assessments (Limited PA includes assessments of HEENT, cardiovascular, 
abdominal systems). A full or limited exam may be conducted at the follow-up visit.  
d. Vital signs include blood pressure, respiration rate, heart rate and temperature.   Note: temperature is collected at screening, pre-dose, at the 
conclusion of dosing day and at the follow-up visit (and not during multiple timepoints on dosing day). Whenever possible, the subject should 
be resting for approximately 5 minutes prior to all measurements.   Vital signs will be collected at screening, pre-dose and at the following 
post-dose timepoints: [6, 11, 16 min (±1 min)]; [35, 65, 95, 125, 185, 245, 305, 365, 485 min (±5 min)].  
e. Height and Weight should be measured at screening and weight only verified on dosing day 
f. 
Clinical laboratory assessments will be analyzed by a central laboratory and consist of the measurements noted in Table 8. Coagulation panel will be 
conducted at Screening, pre-dose, and as part of the post-dose draw clinical labs. 
g. Measurements of melanin content and erythema in the skin will be taken prior to sensor placement at locations on the skin where the sensor(s) 
will be placed, each time a sensor is removed or becomes detached, and at the final removal 
h. Photographs (digital) may be taken of the sensor once it is affixed to the skin. Subject faces or identifying features will not be included in the 
photographs. 
i. 
ORFM data collection will commence prior to dose administration. At least 15 minutes prior to dosing, sensors should be placed on the subject 
and the ORFM device started. Data collection will continue through 8 hours of PK sampling.  
j. 
MB-102 will be administered via IV bolus injection over a 30 second injection period. This will be followed by a 10 mL saline flush over 30 
seconds. Time of administration will be recorded.  
k. PK blood draws will be collected at the following timepoints: pre-dose and 5, 10, 15; (± 1 or 2 min), 30, 60, 90, 120, 180, 240, 300 (±5 min), 
360, 480 (±10 min) minutes post dose.  Blood draws should be via a venous catheter and will be processed in accordance with instructions 
available in the Study Procedure Manual.  
l. 
A 12 lead ECG will be performed at Screening, Pre-dose, and at the following post-dose time-points: 55 min (± 5 min), 115 min (± 5 min), 
235 min (±5 min) and 460 min (±10 min). 
m. Subjects will be required to consume 240 mL of ambient temperature water approximately 1 hour prior to dosing and again at approximately 
30 minutes prior to dosing. Following dosing, water consumption will be permitted ab libitum. A standard meal will be provided as a 
breakfast, lunch and dinner at appropriate times during the dosing day. Snacks and juice drinks may also be provided.  
n. Concomitant medications administered within 7 days prior to baseline through the final follow-up visit will be recorded.   
 
 
 




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Table 5 Legend Group 3, SOG Cohort, SeVG-1, SeVG-2, Cohort 6, Cohort 7 (Single Dose Subjects) and Cohort 8, 8A and 8B  
a. Consent is prior to any study related procedures being conducted. 
b. Negative pregnancy serum human chorionic gonadotropin (hCG) test at screening for women of childbearing potential (WOCBP) is required 
for eligibility and at the follow-up visit. On dosing day, a urine pregnancy test will be conducted for WOCBP  
c. A full physical examination (PE) is required at the screening visit.  A full PE or limited physical assessment (PA) may be conducted prior to 
dosing and (if symptoms direct) within the last 2 hours of the first treatment day (Limited PA includes assessments of HEENT, cardiovascular, 
abdominal systems). A full or limited exam may be conducted at the follow-up visit.  
d. Vital signs include blood pressure, respiration rate, heart rate and temperature.   Note: temperature is collected at screening, pre-dose, at the 
conclusion of dosing day and at the follow-up visit (and not during multiple timepoints on dosing day). Whenever possible, the subject should 
be resting for approximately 5 minutes prior to all measurements.   Vital signs will be collected at screening, pre-dose and at the following 
post-dose timepoints: [6, 11, 16 min (±1 min)]; [35, 65, 95, 125, 185, 245, 305 min (+5 min)]; 365, 485, 605 and 725 min (±10 min)]. 
Subjects enrolled in Cohort 8A will have additional vital signs measured at [965 (±10 min)] and [1445, 1925, 2405, 2885 min (incl. temp) 
(±30 min)]. Vital signs for subjects in Cohort 8B will stop at 24 hours.  
e. Height and Weight should be measured at screening and weight only verified on dosing day 
f. Clinical laboratory assessments will be analyzed by a central laboratory and consist of the measurements noted in Table 8. Coagulation panel 
will be conducted at Screening, pre-dose, and as part of the post-dose draw clinical labs (at the end of treatment day 1). 
g. Measurements of melanin content and erythema in the skin will be taken prior to sensor placement at locations on the skin where the sensor(s) 
will be placed, each time a sensor is removed, replaced or becomes detached, and at the final removal 
h. Photographs (digital) may be taken of the sensor once it is affixed to the skin. Subject faces or identifying features will not be included in the 
photographs. 
i. 
ORFM data collection will commence prior to dose administration. At least 15 minutes prior to dosing, sensors, including an adhesive clip to 
secure the sensor cable [cohort 7 and 8 subjects enrolled under protocol version 11], should be placed on the subject and the ORFM device 
started. Data collection will continue through 12 hours (or 24 - 48 hours for Cohort 8, 8A or 8B) of PK sampling.  
j. 
MB-102 will be administered via IV bolus injection over a 30 second injection period. This will be followed by a 10 mL saline flush over 30 
seconds. Time of administration will be recorded. Subjects in Cohorts 7 and 8 (and a subset of the SeVG cohort) will receive a fixed dose of 7 
mL (130 mg). 
k. PK blood draws will be collected at the following timepoints: 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.  Subjects enrolled in Cohort 8 and 8A will have additional PK sampling at [960 (16 hrs), 
1440 min (24 hrs), 1920 min (32 hrs) and 2400 (40 hrs) 2880 min (48 hrs) (±30 min)]. Those in Cohort 8B will have draws stopping at 24 
hours. Blood draws should be via a venous catheter and will be processed in accordance with instructions available in the SPM.  
l. 
A 12 lead ECG will be performed at Screening, Pre-dose, and at the following post-dose time-points: 55 min (± 5 min), 115 min (± 5 min), 
235 min (±5 min), and 740 min (±10 min). Subjects enrolled in Cohort 8 will have an ECG performed at 1420 min and 2860 min (±30 min) 
m. Subjects will be required to consume 240 mL of ambient temperature water approximately 1 hour prior to dosing and again at approximately 
30 minutes prior to dosing. Following dosing, water consumption will be permitted ab libitum. A standard meal will be provided as a 
breakfast, lunch and dinner at appropriate times during the dosing day. Snacks and juice drinks may also be provided.  
n. Concomitant medications administered within 7 days prior to baseline through the final follow-up visit will be recorded.   




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Table Legend for Group 3 Cohort 7 (including subsets 7A and 7B) (Multiple Dose Subjects with 24/36 hour follow-up) 
a. Consent is prior to any study related procedures being conducted. 
b. Negative pregnancy serum human chorionic gonadotropin (hCG) test at screening for women of childbearing potential (WOCBP) is required for 
eligibility and at the follow-up visit. On dosing day, a urine pregnancy test will be conducted for WOCBP who agree to use an acceptable method of 
birth control  
c. A full physical examination (PE) is required at the screening visit.  A full PE or limited physical assessment (PA) may be conducted prior to dosing 
on each day and within 2 hours of completion of the dosing day (if symptoms direct). (Limited PA includes assessments of HEENT, cardiovascular, 
abdominal systems). A full or limited exam may be conducted at the follow-up visit.  
d. Vital signs include blood pressure, respiration rate, heart rate and temperature.   Note: temperature is collected at screening, pre-dose (for both doses), 
at the conclusion of dosing day and at the follow-up visit (and not during multiple timepoints on dosing day). Whenever possible, the subject should 
be resting for approximately 5 minutes prior to all measurements.   Vital signs will be collected at screening, pre-dose and at the following post-dose 
timepoints: [6, 11, 16 min (±1 min)]; [35, 65, 95, 125, 185, 245, 305 min (+5 min)]; 365, 485, 605, 725 min (+10 minutes). Additional vital signs 
will be collected prior to the 2nd dose being administered. Vital signs will be collected at the following timepoints after the 2nd dose is given: [6, 11, 
16 min (±1 min)]; [35, 65, 95, 125, 185, 245, 305 min (+5 min)]; 365, 485, and 605 (+10 min).  Note: for Cohort 7 and 7A, the 2nd dose is 
administered 12 hours after the first; for cohort 7B, the 2nd dose is administered 24 hours after the first dose.  
e. Height and Weight should be measured at screening and weight only verified on dosing day. For Cohort 7A (enrolled under Amendment 12) and 
Cohort 7B, weight will also be recorded on dosing day.  
f. 
Clinical laboratory assessments will be analyzed by a central laboratory and consist of standard chemistry, hematology and urinalysis parameters 
(Table 8). Coagulation panel will be conducted at Screening only, pre-dose and as part of the follow-up labs on dosing day. Labs will be drawn pre-
dose and at 720 minutes (± 10 minutes) post dose 1.  
g. ORFM data collection will commence prior to dose administration. At least 15 minutes prior to dosing, sensors, including an adhesive clip to secure 
the sensor cable [cohort 7 subjects enrolled under protocol version 11], should be placed on the subject and the ORFM started. Data collection will 
continue through the duration of PK sampling out to 10 hours even if the device indicates transdermal MB-102 can no longer be detected.  
h. MB-102 will be administered as a fixed dose of 7 mL (130 mg) via IV bolus injection over a 30 second period. This will be followed by a 10 mL 
saline flush over 30 seconds. Time of administration will be recorded. The 2nd dose administered will also be a fixed dose of 7 mL (130 mg) 
delivered as described above. All subjects in Cohort 7/7A will have a 2 hour wash-out period after the 10 hour PK mark; subjects in Cohort 7B will 
have a 12 hour wash-out period after the final dose 1 PK collection. Preparation of the subject for the 2nd dose should start at approximately 11.5 
hours from the first dose for Cohort 7/7A.  The original sensor will remain attached to the subject in Cohorts 7/7A.   
i. 
PK blood draws will be collected at the following timepoints: pre-dose and 5, (±1 min), [for Cohort 7A and 7B, a 60 minute PK sample will also be 
collected], 120, 180, 240, 300, (±5 min), 360, 480 and 600 (±10 min). For Cohort 7B, a PK draw will also be performed at 720 min (±10 min).    
A pre-dose 2 blood draw will be collected prior to the 2nd dose.  Blood draws will re-start after the administration of the 2nd dose and be collected at 
the following timepoints: 5, (±1 min), [for Cohorts 7A and 7B, a 60 minute PK sample will also be collected], 120, 180, 240, 300 (±5 min), 360, 
480, 600 (±10 min)].  Blood draws should be via a venous catheter and will be processed in accordance with instructions available in the Study 
Procedure Manual.  
j. 
A 12 lead ECG will be performed at Screening, Pre-dose, and at the following post-dose time-points: 55 min, 115 min, 235 min (±5 min) and at 730 
min (± 10 min). After the 12 hour rest for Cohort 7B, a pre-2nd dose ECG will be performed.  Post-2nd dose ECG collection will follow the same 
timepoints:  55 min, 115 min, 235 min (±5 min), and 610 (± 10 min). Subjects should be resting quietly for 10-15 minutes prior to the ECG 


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collection.  
k. Concomitant medications administered within 7 days prior to baseline through the final follow-up visit will be recorded.   
l. 
Adverse events are collected from the time of dosing through the follow-up visit. 


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6.2 
Screening  
Screening will occur within 40 days (but at least 2 days prior to) the baseline / dosing day and 
will comprise of the following: 
• Obtain written informed consent before any study-specific assessments are performed 
• Assess eligibility against the inclusion and exclusion criteria 
• Collect demographic data and medical history 
• Obtain screening non-fasting laboratory tests including chemistry, hematology, lipid and 
coagulation profile (See Section 7.1.2.6 and Table 8.  Test for Hepatitis B/C, perform 
serum pregnancy test in women of child-bearing potential and collect a urine sample for 
urinalysis. 
• Based on the results of the screening creatinine, calculate eGFR using the CKD-EPI 
equation (Levey, et al., 2009); or (for Group 2 and 3) record a historical eGFR available 
within 40 days of screening 
• Collect height and weight measurements  
• Perform a full physical exam and collect vital signs including temperature (Sections 
7.1.2.7 and 7.1.2.8) 
• Perform a 12 lead ECG (Section 7.1.2.9) 
• Review concomitant medications for exclusionary medications and stability of over the 
counter (OTC) and prescription drugs 
• Document Fitzpatrick Skin Scale Color Type (Appendix A Fitzpatrick Scale) 
• Subjects should be reminded to drink 240 mL of water approximately 1 hour prior to 
their scheduled dosing time (therefore subjects should be encouraged to drink this prior to 
coming to the study site on dosing day).  
6.3 
Dosing Day: Baseline Assessments 
Baseline assessments will be performed prior to dosing. Some assessments (subject eligibility 
review, medical history update, concomitant medication review, ECG and physical exam) may 
be performed the night prior to dosing for subjects brought into the study centers overnight. 
Vitals must be recorded prior to MB-102 administration.  
• Update medical history with any new information or issues occurring since the initial 
screening visit.  
• Review subject eligibility 


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• For subjects enrolled in Cohort 7A (Protocol version 13.0) and Cohort 7B, a weight will 
be collected 
• Confirm that the subject has consumed 240 mL of ambient water at least 1 hour prior to 
dosing time.  
• A venous catheter should be placed in one arm for PK blood draws.  A pre-dose baseline 
draw should be collected.  
• A second catheter should be placed in the opposite arm for dosing of MB-102 and 
iohexol (Groups 1 and 2 only). Following dose completion, this catheter can be removed.  
o For Cohort 7A (enrolled under Protocol Version 13.0) and Cohort 7B, a butterfly 
catheter will be used for MB-102 dosing.  
• Obtain baseline laboratory tests including chemistry, lipids, hematology, coagulation and 
urinalysis (Section 7.1.2.6 and Table 8).  
• Perform a limited physical assessment and collect vital signs (including temperature) 
(Sections 7.1.2.7 and 7.1.2.8). Ensure the subject’s weight has remained consistent since 
screening.  
• Record concomitant medications taken within 7 days of the baseline visit 
• Perform a 12 lead ECG (Section 7.1.2.9)  
• Prior to dosing, have the subject consume 240 mL of ambient water 
• A pre-dose urine sample will be collected in accordance with the instructions in the Study 
Procedure Manual. The total volume of urine excreted from this sample until 12 hours 
post-dose will be recorded or out to 48 hours for the extended PK group. Urine PK 
sampling applies to Group 1 and 2 only (urine PK will not be performed for Group 3 
subjects). 
• For WOCBP, a urine pregnancy test will be performed 
• For Group 3 subjects only: Mexameter readings of melanin and erythema will be 
measured at the intended site of sensor placements.  
• Prior to dosing, the device sensors should be attached to the subject (one probe on the 
sternum, and for some subjects, a second on an assigned location) and ORFM data 
acquisition initiated.  
o For subjects in Cohort 7 and 8 subset cohorts (7A, 7B, 8A and 8B) the additional 
sensor will be placed (the 2-Part Brilliance Sensor) and data acquisition initiated 


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o Baseline data acquisition for subjects enrolled in Cohorts 7 and 8 may be 
collected for 20 – 90 minute period prior to MB-102 administration. During this 
period, no procedures or assessments should be performed, and subjects will be 
instructed to remain very still.  
• For Group 3 subjects only: photographs of the sensor placement may be collected. 
Photographs will not include any identifying features or the subject’s face.  
6.4 
MB-102 Dosing (All Groups) 
The dose of MB-102 should be available and the dose prepared based on the subject’s weight 
and assignment to dose strata and in accordance with instructions provided in the Study 
Procedure Manual with the exception of the subset of subjects who weigh greater than 110 lbs 
(50 kg) in SeVG cohort who will receive a fixed dose of 130 mg MB-102 (7 mL).  In addition, 
all subjects (regardless of weight) in Cohorts 7 and 8 will receive the fixed dose of 130 mg.  
Final dose calculation should also be based on weight and not volume.  The prepared syringe 
should be maintained at ambient temperature. MB-102 and iohexol dosing (when applicable) 
will be performed in the opposite arm from PK draws whenever feasible.  
Administration of MB-102 will be through a catheter placed in the arm (typically the antecubital 
fossa though other locations are acceptable) of subjects for all cohorts with the exception of 
Cohort 7A (enrolled under Protocol Version 12.0) and Cohort 7B.  Ideally, a 21-gauge needle 
and 10 mL syringe (for subjects receiving the fixed dose) should be used for administration. 
Subjects in Cohort 7A (under Protocol Version 12.0) and Cohort 7B will be dosed via direct IV 
injection through a butterfly catheter.  
• Ensure Universal Standard precautions are taken with handwashing and gloving 
procedures; maintain aseptic technique when handling the prepared syringe 
• The site should ensure patency of the catheter by initially flushing with saline or a 
heparin solution. Assessing patency of the placed catheters every 8 hours or so will also 
ensure ease of the PK draws. Any catheter that shows resistance to flush or if blood is 
unable to be drawn out should be replaced.  
• Prior to MB-102 administration, ensure blood can be removed from the catheter. For 
Cohort 7A (under Protocol Version 12.0) and Cohort 7B subjects, a butterfly catheter will 
be used for MB-102 injection which will be removed from the arm after dosing.  
• Administration of MB-102 should be via a steady bolus injection (without hard pressure) 
over 30 seconds 
• Following MB-102, a 10 mL saline flush should be administered over 30 seconds 
• The injection site should be observed for swelling or induration.  
• For all 2nd dose administration for cohorts 7A and 7B, a different vein in the same arm 
will be used for dosing.  
 
To avoid extravasation/infiltration: 
• Ensure no dislodgement of the catheter or needle cannula during venipuncture 
• Ensure the vein wall is not punctured during placement 
• Ensure appropriately sized catheters are used for the vein size of the subject 


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• Avoid strong pressure on the syringe plunger during saline or MB-102 administration 
 
It is particularly important for site teams to check the patency of catheters used for the second 
MB-102 administration in Cohort 7 subjects receiving a second dose of MB-102. If a catheter is 
determined to be compromised in anyway, another catheter may be placed for dosing in the same 
arm as the original catheter. Note: catheters used for MB-102 dosing should not be re-used for 
PK draws. Cohort 7A (under Protocol Version 12.0) and Cohort 7B subjects will be dosed 
directly via IV injection through a butterfly catheter.  
The time noted at the completion of MB-102 injection is the start-time for the timing of the PK 
draws.  
• Adverse event collection begins 
6.5 
Iohexol Dosing (Groups 1 and 2 only) 
• 5 mL of iohexol will be administered as a bolus via IV over approximately 30 seconds 
• 10 mL saline flush will be administered via IV over approximately 30 seconds 
6.6 
Post-dose Study Procedures 
Post dose study procedures are outlined in Section 13 for each of the various Groups and 
Cohorts:  
• 13.1 Group 1 (Cohorts 1 and 2) and Group 2 (Cohorts 3 and 4 subset) 
• 13.2 Post-Dose Procedures: Group 2 (Cohort 4 Extended PK Subgroup only) 
• 13.3  Post-Dose Procedures: Group 3: Cohort 5 
• 13.4  Post-Dose Procedures: Group 3: SOG 
• 13.5 Post-Dose Procedures: Group 3: SeVG, Cohort 6 and 7, 7A: Single Dose 
Subgroup 
• 13.6 Post-Dose Procedures: Group 3: Cohort 7, 7A and 7B: Multiple Dose Subgroup 
• 13.7 Post-Dose Procedures: Group 3: Cohort 8 and 8A 
• 13.8 Post-Dose Procedures: Group 3: Cohort 8B 
6.7 
Follow-up Visit 
Subjects will return for a safety follow-up visit approximately 7 +/-3 days after dosing. The 
following assessments will be performed 


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• Obtain laboratory tests including chemistry, lipids, hematology and urinalysis [and 
pregnancy test for WOCBP], (Section 7.1.2.6 and Table 8). 
• Perform a full or limited physical exam and collect vital signs including temperature 
(Sections 7.1.2.7 and 7.1.2.8) 
• Record concomitant medications  
• Collect adverse events  
6.8 
Early Withdrawal / Unscheduled Visits 
Any subjects that withdraws from the study early for any reason, or who needs to have an 
unscheduled visit performed to assess a safety issue, will have the following assessments 
performed:  
• Obtain laboratory tests including chemistry, lipids, hematology, and urinalysis profile 
(Section 7.1.2.6 and Table 8). 
•  Perform a full or limited physical exam and collect vital signs including temperature 
(Sections 7.1.2.7 and 7.1.2.8) 
• Record concomitant medications  
• Collect adverse events  
• Record withdrawal date and reason for withdrawal, if appropriate 
7 
Efficacy and Safety Variables  
7.1 
Efficacy and Safety Measurements Assessed and Flow Chart  
Table 4, Table 5, Table 6 and Table 7 in Section 6.1 shows the planned study assessments.   
7.1.1 Efficacy Assessments 
This pilot study is not designed to address treatment efficacy rather it is to evaluate the use of 
MB-102 and the ORFM device to provide a point of care (POC) means to collect GFR data.  
7.1.2 Safety Assessments 
Safety will be monitored by the assessments described below as well as the collection of AEs at 
every visit after screening. Planned safety assessments are detailed in the ORFM Pilot 2 Study 
Schedule (Table 4, Table 5, Table 6 and Table 7). The investigators or site staff will be 
responsible for monitoring the safety of subjects who have entered this study and will be 
responsible for detecting, documenting and reporting events that meet the definition of an 
adverse event (AE) or serious adverse event (SAE).  Significant findings that were noted to be 


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present at or prior to dosing must be included in the relevant medical history page of the eCRF. 
Significant new findings that begin or worsen after dosing must be recorded on the AE page of 
the eCRF. Subjects should be followed until the event is resolved or stabilized. AEs are collected 
from the time of dosing until the completion of the follow-up visit.   
7.1.2.1 Adverse Events 
Adverse Event Definition 
An adverse event is defined as any untoward medical occurrence, unintended disease or injury, 
or untoward clinical signs (including abnormal laboratory findings) in subjects, temporally 
associated with the use of a medicinal product, whether or not related to the investigational 
medical device or drug. 
An unanticipated adverse device effect (UADE) is any serious adverse effect on health or safety, 
any life-threatening problem or death caused by, or associated with a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
application; or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects. For the purposes of this trial, the device is the ORFM 
and the sensor system including the adhesive pads for the attachment of the optical sensors to the 
body. 
Documentation and Reporting of Adverse Events 
AEs should be reported and documented in accordance with the procedures outlined below. The 
following data should be documented for each AE: 
• Description/term of the symptom event (underlying diagnosis) 
• Date of first occurrence and date of resolution (if applicable) 
• Classification of “serious” or “not serious” (Section 7.1.2.2) 
• Severity 
• Causal relationship  
• Action taken 
• Outcome of event  
For abnormal clinically significant laboratory findings, the clinical manifestation (diagnosis) 
should be noted as an adverse event (e.g. anemia instead of low hemoglobin). Should a clinically 
significant lab abnormality occur that is not part of a diagnosis, the abnormality itself may be 
reported as an AE. Laboratory abnormalities that meet the criteria for an AE should be followed 
until they have returned to normal or an adequate explanation of the abnormality is determined. 
When an abnormal laboratory result corresponds to a sign/symptom of an already reported AE it 
is not necessary to separately record the lab result as an additional AE.   


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Assessment of Severity 
Each AE will be assigned a category by the investigator as follows: 
• Mild: results in minimal transient impairment of a body function or damage to a body 
structure and/or does not require any intervention other than monitoring or OTC 
medication.  
 
• Moderate: Results in moderate transient impairment of a body function or transient 
damage to a body structure and/or requires intervention, such as administration of 
medication or transfusion or laparoscopic or endoscopic procedure to prevent permanent 
impairment of a body function or damage to a body structure.  
 
• Severe: An event which is life threatening, results in permanent impairment of a body 
function or permanent damage to a body structure or necessitates significant intervention, 
such as major surgery, to prevent permanent impairment of a body function or permanent 
damage to a body structure.  
The term severe is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe headache). This is not the same as serious, which is based 
on patient/event outcome or action criteria usually associated with events that pose a threat to a 
patient‘s life or functioning. Seriousness (not severity) serves as a guide for defining regulatory 
reporting obligations. 
 
An event that changes in severity (gets worse or gets better) should be noted as its worst severity.  
 
Assessment of Causality 
Every effort will be made by the investigator to assess the relationship of the AE, if any, to the 
study device (and components), investigational drug or the reference standard (iohexol).  
Causality should be assessed using the categories presented below: 
 
Unrelated 
Clinical event with an incompatible time relationship to study device or 
study drug, and that could be explained by underlying disease or other 
drugs or is incontrovertibly not related to the study device. 
Unlikely 
Clinical event whose time relationship to study device investigational 
drug makes a causal connection improbable, but that could plausibly be 
explained by underlying disease or other drugs. 
Possible 
Clinical event with a reasonable time relationship to study device or 
investigational drug, but that could also be explained by concurrent 
disease or other drugs. 


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Probable 
Clinical event with a reasonable time relationship to study device or 
investigational drug, and is unlikely to be attributed to concurrent disease 
or other drugs. 
Very Likely/Certain 
Clinical event with plausible time relationship to study device or 
investigational drug, and that cannot be explained by concurrent disease 
or other drugs. 
AEs that are deemed related should be further assessed to determine if a relationship to the 
investigational drug, device or reference standard can be elucidated.  
Action Taken 
The investigator will describe the action taken in the appropriate section of the eCRF, as follows: 
• None 
• Concomitant interventional treatment(s) administered (includes medications or 
procedures) 
• Other, specify 
Outcome of the Event 
The investigator will describe the outcome of the event in the appropriate section of the eCRF, as 
follows: 
• Unknown 
• Resolved 
• Ongoing 
• Resolved with sequelae 
• Death (with date and cause reported) 
Follow-up of Adverse Events 
Subjects with AEs should be followed until the event is resolved or until, in the opinion of the 
investigator and medical monitor, the event is stabilized or determined to be chronic. 
7.1.2.2 Serious Adverse Events 
Serious Adverse Event Definition 
An SAE is any AE from this study that results in one of the following outcomes: 
 
An adverse event that:  
a) led to death;  
b) led to serious deterioration in the health or the subject, that either resulted in: 
  


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1) a life threatening illness or injury or  
2) a permanent impairment of a body structure or a body function, or 
3) in-patient or prolonged hospitalization, or 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function; 
 
c) led to fetal distress, fetal death or a congenital abnormality or birth defect 
 
Reporting requirements for all SAEs is detailed in Section 7.1.2.3.  
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the 
protocol without serious deterioration in health, is not considered a serious adverse event. 
 
7.1.2.3 Reporting of Serious Adverse Events  
Any SAE must be reported by the investigator if it occurs during the clinical study whether or 
not the event is considered to be related to the ORFM device, investigational drug or reference 
standard.  All serious adverse events must be reported by the Investigator (or designee) by 
submitting the Serious Adverse Event Report Form to the Sponsor or designee, within 24 hours 
of learning of the adverse event.   
The Sponsor, or their designee, in cooperation with the Investigator, will assess all serious 
adverse events considered device-related for potential reportability to regulatory authorities and 
ethical committees as an Unanticipated Adverse Device Effect (UADE) or as an expedited 
serious adverse event.  
Note: It is also the responsibility of the Investigator to inform their Independent Ethics 
Committee (IEC) of other serious adverse events (i.e. non-UADEs) as required by their IEC 
procedures and in conformance with regulations. 
 
SAEs must be reported on an SAE Report Form via email within 24 hours of site 
knowledge to: CLINCALSTUDIES@MEDIBEACON.COM 
 
The investigator should not wait to receive additional information to document fully the event 
before notification to the Sponsor of an SAE, though additional information may be requested.  
Where applicable, information from relevant laboratory results, hospital case records, and 
autopsy reports should be obtained. 
Instances of death, congenital abnormality, or an event that is of such clinical concern as to 
influence the overall assessment of safety, if brought to the attention of the investigator at any 
time and linked by the investigator to this study, should be reported to MediBeacon.   
The sponsor or designee will promptly notify all relevant investigators and the regulatory 
authorities of findings that could adversely affect the safety of subjects, impact on the conduct of 
the study or alter the IEC approval/favorable opinion of the study.  In addition, the sponsor, will 
expedite the reporting to all concerned investigators, to the IECs, and to the regulatory 
authorities of all adverse device reactions that are both serious and unanticipated.   


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7.1.2.4 Pregnancies 
Testing for pregnancy for a female study subject with childbearing potential must be conducted 
at screening (or within 7 days of dosing).  Subjects who are pregnant or intend to become 
pregnant during the study should be excluded. Should a pregnancy occur with a study subject, 
the pregnancy should be reported to MediBeacon within 24 hours of the site’s knowledge on the 
appropriate form in the Study Procedure Manual. All pregnancies will be followed to term, 
delivery or premature termination.  Additional follow-up will occur for 3 months post-partum.   
Pregnancies should be reported via email to:  CLINCALSTUDIES@MEDIBEACON.COM 
7.1.2.5 Device Observations / Malfunctions  
All device observations, malfunctions or failures of the ORFM device will be documented in the 
eCRF.  
 
7.1.2.6 Clinical Laboratory Evaluation 
All clinical laboratory assessments will be performed by a central lab. Reference ranges will be 
provided to the site and used by the investigator to assess the laboratory data for clinical 
significance and pathological changes relative to baseline measurements.  The following 
laboratory tests will be performed as indicated in Table 8 at timepoints outlined in Table 4, 
Table 5, Table 6 and Table 7. 
Table 8 Summary of Clinical Safety Laboratory Assessments 
All lab tests are non-fasting.  
Chemistry Panel                                   
Hematology       
Other required lab tests 
• 
Alkaline Phosphatase  
• 
Alanine Aminotransferase (ALT) 
• 
Albumin 
• 
Aspartate Aminotransferase (AST) 
• 
Bilirubin (total and direct) 
• 
Blood Urea Nitrogen (BUN) 
• 
Calcium (Ca) 
• 
Carbon dioxide (CO2) 
• 
Chloride (C) 
• 
Creatinine (SCr) 
• 
Glucose 
• 
Phosphorus 
• 
Potassium  
• 
Sodium 
• 
Total Protein 
• 
Uric acid 
• 
BUN/Creatinine ratio 
Lipids 
• 
Cholesterol 
• 
Triglycerides 
 
• 
Hematocrit 
• 
Hemoglobin 
• 
WBC 
• 
RBC 
• 
Platelets 
Differentials 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
 
 
For WOCBP 
• 
Serum pregnancy test (screening 
and a urine dipstick on day of 
doing; and serum at the follow-up 
visit 
Urinalysis  
• 
Protein 
• 
Glucose 
• 
Acetone 
• 
Hemoglobin (blood) 
• 
Bilirubin 
• 
Urobilinogen 
• 
Acetone 
• 
Nitrite 
• 
Leucocytes 
• 
pH 
• 
Specific gravity 
• 
Color 
• 
Bacteria (when indicated) 
If abnormalities are seen, then 
microscopic examination will be 
performed 


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Chemistry Panel                                   
Hematology       
Other required lab tests 
Coagulation Parameters 
Only performed at screening and on 
dosing day 
• 
PT 
• 
INR 
• 
aPTT 
 
7.1.2.7 Vital Signs 
Vital signs (including blood pressure, heart rate, respiration, and temperature) will be measured 
at screening, at multiple timepoints on dosing day (see Section 13), and at the follow-up visit. 
Vital signs should be collected while the subject is in a seated position and after resting for 
approximately 5 minutes for all measurements.  Temperature is only collected at screening, pre-
dose, and the completion of the dosing day, and at the follow-up visit. In the extended PK group 
(Group 2) and Cohort 8 (Group 3), temperature is also taken at 1445 minutes (after the 24 hour 
PK collections).  
7.1.2.8 Physical Examinations or Limited Physical Assessments 
Physical examinations (when conducted by a physician) or limited physical assessments (when 
conducted by a nurse or other qualified personnel) should include at a minimum an assessment 
of the head, ears, eyes, nose, throat (HEENT), respiratory, cardiovascular, and gastrointestinal 
systems. It is preferred that the same medical professional perform the baseline and post dosing 
assessments. Significant findings that were present prior to dosing must be included in the 
Medical History eCRF page. Significant new findings that begin or worsen after dosing must be 
recorded on the AE page of the eCRF. Clinically significant abnormalities occurring post-dose 
should be evaluated by a physician and noted as AEs.   
The study physician will assess the subject for the occurrence of clinically significant new 
findings that begin or worsen after dosing which must be recorded as an AE on the eCRF page. 
A full physical exam should be conducted at screening and limited physical assessments may be 
conducted at other time points and must also be inclusive of the relevant organ or body system of 
interest for assessing the AE 
7.1.2.9 ECGs 
Standard 12 lead ECGs will be collected at screening and various timepoints on dosing day (see 
(Table 4, Table 5, Table 6 and Table 7) and during the 48 hour period for Extended PK group 
(Group 2) and Cohort 8 (Group 3). The following parameters will be assessed: interpretation, 
ventricular rate, PR interval, QRS duration, QT, and QTcF.  
 
Subjects should be allowed to rest quietly approximately 10-15 minutes prior to their ECG.  
Post-dose ECGs are timed to allow for this. Additional ECGs may be collected if an issue or 
safety concern is noted.  
 
An appropriately trained and experienced physician will interpret the ECGs.  A subject with an 


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abnormal clinically significant ECG at baseline or prior to dosing does not qualify for the study.  
A subject with an abnormal not clinically significant ECG does not qualify without investigator 
comment on the ECG source document/eCRF.  
 
For changes that are clinically significant, the investigator is to continue to monitor the subject 
until the change returns to normal, or until the investigator determines that follow-up is no longer 
medically necessary, or the subject is referred to his/her primary care physician.  If the 
investigator determines the change is not clinically significant, the investigator’s evaluation will 
be documented on the ECG source document and no further action is required. ECGs with 
clinically significant abnormalities will also be reviewed by a cardiologist.  
 
7.1.2.10 PK Sample Collection 
PK samples will be collected at the timepoints noted in Section 13.  Recommendations for 
venous access and sample processing information is available in the Study Procedure Manual.  
 
7.1.2.11 Urine Collection 
The total volume of urine excreted from the time starting pre-dose through 12 hours (or 48 hours 
for the extended PK subgroup) will be recorded for subjects enrolled into Groups 1 and 2 only. A 
sample will also be collected in accordance with the instructions provided in the Study Procedure 
Manual.  
 
8 
Information for the Investigator: Potential Risks of the Device 
Adverse events that may be anticipated in this clinical study are outlined for the Investigational 
Drug, the ORFM Device and the Reference Standard (iohexol). 
 
8.1 
Investigational Drug 
Clinical data from the Pilot 1A and 1B studies (total n = 32 subjects) included the following 
adverse events:  
• Pilot 1A 
o Vasovagal reaction (1 subject) 
o Dizziness (1 subject, 2 events) 
 
These events occurred in fasting subjects shortly after dosing and resolved on that day.  No other 
AEs, injection site reactions, clinically significant laboratory values or significant changes in 
vital signs were noted during this study.  
 
• Pilot 1B 
o Headaches (56.3% of subjects) 
o Erythema (at the site of the adhesive) (100% of subjects) 
o Diarrhoea (1 subject) 
o Dizziness (occurring in 1 subject following release from the study center) 
 


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Erythema was thought to be related to the adhesive used to adhere the sensor to the skin. 
Headaches were deemed related to the head strap required to hold the forehead sensor in place.   
 
MB-102 is excreted in the urine. Therefore, urine discoloration is expected but has not been 
considered an adverse event in prior studies.  
 
In the ongoing Pilot 2 study, a total of 202 subjects with normal to compromised renal function 
have been exposed to MB-102. A total of 120 subjects received a dose of 4 µmol/kg followed by 
a 5 mL injection of iohexol. Seventy (70) subjects received a single dose only (no iohexol) of 4 
µmol/kg of MB-102) and 12 have received a fixed dose of 130 mg (7 mL). All reported AEs 
were mild or moderate in severity and resolved without sequalae.  Overall, MB-102 given in 
conjunction with or without iohexol was well tolerated in this subject population.  
 
A total of 33 adverse events were reported in 22 treated subjects in Groups 1, 2 and 3 (Cohorts 5, 
6 SOG and SeVG only) for an AE rate of 10.9% in the treated population. A total of 24 events in 
19 subjects were considered mild and 9 moderate events occurred in 5 subjects (2.5% of the 
population). There were no severe events reported. There were no Serious Adverse Events 
(SAEs) reported during the study. There were no Unanticipated Adverse Device Effects 
(UADEs) reported during the study.  
 
Four AEs, dyspepsia, chromaturia, hot flush and (facial) rash were considered related to 
investigational product (MB-102); all events resolved by study completion. Dyspepsia and 
chromaturia were also considered to be related to iohexol. Of note, chromaturia is an expected 
effect of MB-102 and expected in all subjects as the excretion of MB-102 will color the urine of 
subjects receiving the product. It is not a documented effect of iohexol (per the label).   
 
Seven (7) AEs occurring in 7 subjects were considered related to the device (sensor attachment); 
these included application site erythema, dermatitis, and pruritus and were considered related to 
the adhesive material used to hold the sensor in place. Two events of application site 
discoloration (melanin spot at the sensor location) were noted in 2 subjects in the SOG cohort 
which resolved within 24 hours of removal of the sensor.  Other reported AEs (conjunctivitis, 
nausea, vomiting, cardiac murmur, headache, anxiety, micturition urgency, pollakiuria, urine 
odor abnormal, peripheral oedema, fatigue, and a pruritis event [not at the sensor location] were 
considered not related to MB-102, the sensor device or iohexol.  Injection site reactions 
(bruising, erythema, extravasation) were also not considered related to MB-102.   
 
There may also be other risks that are unforeseen at this time. For additional information on the 
risk profile, please reference the current Investigator’s Brochure.  
 
8.2 
ORFM Device 
There are no direct risks associated with the ORFM device (console) as it does not contact the 
study subject.  Adverse events observed from the sensors are with regard to the methods used to 
affix it to the study subject including head straps and adhesive tape (see Section 8.1).    


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8.2.1 Adhesive Clip 
As with the adhesive used on the sensors, there is the chance of reaction to the adhesive used to 
attach the clip to the skin.  Reactions could include redness, itchiness or other localized skin 
reactions. 
8.2.2 2-Part Brilliance Sensor 
The 2-Part Brilliance Sensor includes a removable adhesive ring that will allow re-use of the 
sensor itself.  There are no direct risks associated with the 2-Part Brilliance Sensor. As with the 
other devices described above, skin reactions may be seen to the adhesive used to hold the sensor 
in place.  
8.3 
Reference Standard 
Risks associated with the reference standard iohexol (Omnipaque™ 300 are detailed in the 
current version of the Package Insert (Appendix B).  
It should be noted that the dose level of iohexol (5 mL) is significantly lower than the doses used 
for contrast imaging. A published study by Nilsson-Ehle in over 8000 patients using iohexol to 
measure kidney function reported “an extremely low toxicity” related to the small doses of 
iohexol administered. He reported very few adverse events compared to typical radiographic 
imaging studies (e.g. CT study, urography, angiography) where much larger volumes of iohexol 
may be used (i.e. 10-50 times). The author reported “no complications in 8000 investigations 
except for 2 patients who reported malaise and vomiting between 1 to 3 hours after injection of 
iohexol” and they concluded that they did not know if these adverse effects were related to their 
procedure.  
8.4 
Trial Procedures 
The study will collect approximately 135 mL of blood on dosing day (PK draws and lab draws) 
for a standard subject in Group 1 and 2, and Group 3 Cohorts 6, SOG and Cohort 7 (Single Dose 
Subjects) and slightly less volume for Group 3 Cohort 5 subjects.  Subjects in the extended PK 
subgroup (Group 2) will have approximately 165 mL of blood collected over a 48-hour period. 
Multiple dose subjects from Cohort 7 will have approximately 146 - 154 mL of blood collected 
(PK collection is reduced in this group). Blood collection may lead to light-headedness and 
dizziness in some study subjects. It is recommended to ensure subjects continue to hydrate and 
eat during dosing day to mitigate the effect of blood loss.  
Bruising and pain at the site of the venous catheters may also be expected.  


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9 
Statistical Methods 
9.1 
Statistical and Analytical Plans  
9.1.1 Datasets or Populations Analyzed 
Safety Analysis Set:  The Safety Analysis Set (SAF) will consist of all subjects who sign the 
Informed Consent and receive study drug in the study. All safety analyses will be performed on 
the safety analysis set. 
Per Protocol Set: The Per Protocol Set (PP) will consist of all subjects who receive the 
investigational drug and have no major protocol deviations. Demographic and Other Baseline 
Characteristics including Subject’s age, race, sex, weight, body mass index (BMI), baseline CKD 
status, and medical history will be recorded at screening and summarized for the Safety and Per 
Protocol Sets.   
9.1.2 Subject Disposition 
The number and percentage of subjects who complete the study or who terminate early from the 
study and the reasons for early termination will be collected and reported.  Subjects will be 
considered to have completed the study if they complete the dosing day.  
The number and percentage of subjects in each analysis population will be presented.  
Percentages will be based on the number of subjects enrolled. 
9.1.3 Pharmacokinetic Assessments 
Pharmacokinetic parameters for MB-102 and iohexol will be calculated using both 
compartmental and non-compartmental techniques.  Data from the patients in Cohort 1 that were 
used for dose ranging for MB-102 will have their data dose normalized to be consistent with the 
dose used for the remainder of the study.  All pharmacokinetic assessments will be performed 
using Phoenix WinNonlin (and possibly Phoenix NLME) Build 6.4.0.768. 
 
Non-compartmental analysis (NCA) will be performed on data for both MB-102 and iohexol.  
The following parameters will be determined: 
 
• Cmax – the maximum plasma concentration obtained during the sampling interval 
•  Tmax - the time at which Cmax occurred 
• λz – the terminal rate constant will be determined by linear regression of the terminal 
linear phase of the log plasma concentration-time profile.   
• AUClast - Area under the plasma concentration-time curve from the time zero to the time 
of the last quantifiable concentration.   
• AUC∞ - Area under the plasma concentration-time curve from time zero to infinity. 
(AUC∞) 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 


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concentration.   
• t1/2 λz – the elimination half-life will be calculated as t1/2 λz= ln(2)/ λz .  
• Clp – Total plasma clearance will be calculated as: Clp  = Dose/ AUC∞.  
• CLr - Renal clearance will be calculated as: CLr = Ae/ AUClast, where Ae is the 
cumulative amount of analyte excreted in urine over the sampling interval. 
 
In addition to the NCA analysis described above, a compartmental analysis will be performed 
separately for each subject’s profile.  Based on prior data, it is expected that a two 
compartmental model will provide an adequate fit.  In addition, a population fit may also be 
attempted. 
 
Observed plasma and urine concentrations will be summarized descriptively by time point and 
agent (MB-102 or iohexol) for all subjects included in the pharmacokinetic analysis.  In addition, 
plots of mean concentrations over time will be provided by agent, including standard error bars 
around the mean values. 
 
All derived results for pharmacokinetic parameters will be summarized numerically by agent.    
For categorical variables, the frequency of subjects will be provided along with the percentage 
based on the number of subjects with available data. Summaries will be based on observed data 
(i.e., no missing data will be imputed) and will include all dosed subjects completing all aspects 
of the study. 
 
An analysis of variance of estimated GFR will be performed taking into account the factors 
subjects, treatments (MB-102 and iohexol), CKD stage and skin color type.  
 
All plasma and urine concentrations will be provided in listings by subject and time point. Any 
blood measurements obtained outside of the defined windows around the scheduled time point 
will be identified as protocol deviations. Additionally, pharmacokinetic parameters will be 
provided in listings sorted by subject. 
 
9.1.3.1 Analysis of ORFM Fluorescence Data (tGFR) vs PK Data for GFR Determination 
A correlation between the fluorescence intensity and tracer concentration at each time point in 
the renal excretion phase will be performed to establish that the transdermal fluorescence 
pharmacokinetics matches the plasma pharmacokinetics. Summaries of the data will be 
performed to evaluate the effects of skin color and CKD stage on the correlation.  
 
Data from a Pilot 1B study shows that plotting plasma concentration versus fluorescence 
intensity at the same time points in the renal excretion phase yields a tight correlation (Figure 2). 
The data shown in this correlation are from healthy subjects with normal renal function 
(measured by eGFR) who received a 4 μmol/kg dose. 


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Figure 2 Correlation between Plasma Pharmacokinetics and Fluorescence Pharmacokinetics in Pilot 1B, 
Subject 12 
 
 
In the Pilot 2 Group 1 clinical study, this type of correlation was observed across subjects with 
GFR values over the entire range. Examples are shown below (Figure 3): 
 
Figure 3 Transdermal fluorescence correlates with plasma Pharmacokinetics over a range of GFR 
 
 
 


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From the Pilot 2 Group 1 plasma measured GFR from MB-102 and the fluorescence decay 
constant from all subjects, a very preliminary correlation plot has been constructed (Figure 4), 
similar to the graph as done in Rabito et. al. 2010 (Figure 5).   
 
Figure 4 Correlation between Plasma GFR and Trans-cutaneous Fluorescence Clearance Rate (with Volume 
of Distribution (VD) correction of GFR) 
 
 
  
 
 


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Figure 5 Correlation between GFR measured as renal clearance of 125I-iothalamate and the rate of clearance 
of 99mDTPA 
 
 
 
Further analysis of the data will be done to determine the optimum data conversion using volume 
of distribution, body surface area, and possibly other factors. 
 
For Pilot 2 Group 2 subjects, this type of graph will be used to convert the measured 
fluorescence time constant “fluorescence GFR” and then compare that value with the MB-102 
plasma measured GFR from the same subjects. The database will also be updated with this new 
data to make the algorithm more robust for the pivotal studies to follow. 
 
9.1.4 Safety Variables 
The clinical safety measurements include AEs, physical exam findings, vital signs, ECG 
collection, and laboratory tests.  
Treatment-Emergent Adverse Events 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The 
system organ class and preferred term for each AE will be available, along with the verbatim 
reported term, event start and stop dates/times, seriousness, severity, relationship to 
treatment/device, action taken, and event outcome. SAEs will also be documented in a case 
narrative format.  
The overall numbers and percentages of subjects who experienced any treatment-emergent AE 
(TEAE), will be presented.  AEs will be presented by system organ class, and preferred term. 
 
 


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Physical Examinations/Limited Physical Assessments 
The results of physical examinations will be provided in subject data listings for Groups 1 and 2 
and will be collected either as medical history or adverse events for Group 3. All clinically 
significant treatment-emergent abnormalities will be reported as AEs. 
Clinical Laboratory Assessments  
Clinical laboratory tests include clinical chemistry, hematology, urinalysis and coagulation 
parameters. Each parameter will be summarized using the most appropriate descriptive statistics.  
Details will be specified in the Statistical Analysis Plan (SAP).  Also, individual subject results 
will be assessed against an appropriate reference range if available.  The manifestation of any 
clinically significant abnormality that develops during the study will be reported as an AE. 
Prior and Concomitant Therapies 
Concomitant medications administered within 7 days prior to and through follow-up will be 
listed. Medications will be coded using the World Health Organization (WHO) drug dictionary. 
Data will be provided in one or more subject data listings. Concomitant non-drug therapies will 
be listed. 
9.1.5 Study Interim Analysis 
A study interim analysis will be performed after completion of the SeVG cohort of all 
previously collected subject data (Groups 1, 2 and 3 through the SevG enrollment). This 
analysis will be performed to summarize clinical data in support of pivotal regulatory 
discussions. It is not the intention to stop the study early or revise the sample size for the 
remaining cohorts.  
 
9.1.6 Early Termination of the Study 
MediBeacon may terminate this study early if safety considerations arise or for other reasons.  In 
addition, if MediBeacon determines that adequate data are available to continue program 
development, early termination (prior to enrollment of all planned subjects in Group 3) may 
occur.  
9.1.7 Determination of Sample Size 
This is a pilot study therefore no formal calculation of sample size was performed.  
9.1.8 Missing Data 
Missing values will not be imputed. Additional data imputation rules may be specified in the 
Statistical Analysis Plan if needed. 


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10 Quality Assurance and Quality Control 
10.1 Training 
The clinical site will be trained on the protocol and study procedures. In addition, Sponsor 
representatives will be onsite during dosing procedures to operate the ORFM device.  
 
10.2 Audit and Inspection 
The study site and study documentation may be subject to quality assurance audits during the 
course of the study by the sponsor, or its nominated representative.  In addition, inspections may 
be conducted by regulatory authorities at their discretion. 
10.3 Monitoring 
Data for each subject will be recorded in an electronic data capture (EDC) system.   Data 
collection must be completed for each subject enrolled in the study.   
In accordance with GCP and International Conference on Harmonization (ICH) guidelines, the 
study monitor will conduct monitoring visits at regular intervals.  During the visits, the study 
monitor will perform the source document verification and verification that investigator’s 
obligations and all applicable regulatory requirements are being fulfilled.  The frequency of 
monitoring visits will be determined by the rate of subject recruitment.  
The investigator must permit the monitor, the IEC, the sponsor’s internal auditors and 
representatives from regulatory authorities direct access to all study-related documents and 
pertinent hospital or medical records, including direct access to electronic medical records for 
confirmation of data contained within the EDC system.  Subject confidentiality will be protected 
at all times. 
10.4 Data Management and Coding 
MediBeacon or designee will be responsible for activities associated with the data management 
of this study.  This will include setting up a relevant database and data transfer mechanisms, 
along with appropriate validation of data and resolution of queries.  Data generated within this 
clinical study will be handled according to the relevant Standard Operating Procedures (SOPs) at 
MediBeacon or their designee. 
Study sites will enter data into a 21 CRF Part 11 compliant electronic data capture (EDC) system 
via a secure internet connection.  Data entered into the EDC system must be verifiable against 
source documents at the study site. Any changes to the data entered into EDC system will be 
recorded in the audit trail. 
Missing or inconsistent data will be queried via the EDC system to the investigator for 
clarification.  Subsequent modifications to the database will be documented. 


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Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
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10.5 Protocol Deviations 
The Investigator will not deviate from the clinical protocol without the prior written approval of 
MediBeacon except in medical emergencies or in unforeseen, isolated instances where minor 
changes are made that will not increase the subject’s risk or affect the validity of the study.  In 
medical emergencies, prior written approval for protocol deviations will not be required, but 
MediBeacon or their designee must be notified via telephone within 24 hours of occurrence. 
Prospective approval of protocol deviations to recruitment and enrollment criteria (also known as 
protocol waivers or exemptions) are not permitted.  
 
Major Protocol Deviation is a significant deviation from the protocol that may impact subject 
safety and/or affect the integrity of clinical trial data.  These may include, but are not limited to 
the following: 
 
• Improper or inadequate informed consent procedures 
• Subject did not meet eligibility criteria 
• Subject received prohibited concomitant medication(s) at any time during the trial 
• A significant protocol required assessment or procedure was not performed per protocol 
requirements 
• Subject received incorrect study medications at any time during the trial 
• Significant departure from protocol-required dosing 
• Subject developed criteria that required withdrawal from study protocol but was not 
withdrawn 
 
A Minor Protocol Deviation is a deviation that does not impact subject safety and/or compromise 
the integrity of the clinical trial data. 
 
Deviations will be documented at the site and submitted to the IEC (as required) and the sponsor.  
 
10.6 Device Accountability 
ORFM devices and investigational drug MB-102 will be supplied to the clinical site.  During the 
study, used vials of MB-102 should be maintained until reviewed by the clinical monitor. At the 
termination of the study, all devices will be returned to MediBeacon. Unused investigational 
drug may be returned or destroyed following authorization by the sponsor.   The investigator 
must maintain records of receipt, use and disposition of the devices and of the drug as well as the 
reference standard. The following records will be kept: 
 
• Records of devices received, including dates of receipt, quantity, serial number and the 
signature of the person in charge of device accountability. 
• Records of device use, including the subject ID, date of use, and any specific data the 
sponsor requires collected on the device usage form.  
• Records of storage of the investigational agent 
• Records of receipt, use and destruction of the investigational agent 
• Records of use of the reference standard (as applicable) 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 73 of 103 
 
 
10.7 Direct Data Collection 
Fluorescent measurements will be collected directly by the ORFM device prototypes and will not 
appear on any available source documentation. The ORFM computer system will be a closed 
system and direct data output to hard media will be used prior to upload to a secure server for 
analysis. 
 
11 Records / Retention 
Essential documents are those documents that individually and collectively permit evaluation of 
the study and quality of the data produced.  After completion of the study, all documents and 
data relating to the study will be kept in an orderly manner by the investigator in a secure study 
file. All study records will be available for inspection by the sponsor or its representatives, or a 
regulatory agency.  
 
Investigator files containing all records and reports of the investigation should be retained for a 
minimum of two (2) years after the completion/ termination of the investigational study or the 
date that the records are no longer required for purposed of supporting a premarket approval 
application.  The Sponsor will determine with the investigational site as to this exact date so that 
the minimum two-year record retention can be accomplished.  Records may be discarded upon 
written notification by the Sponsor.  To avoid error, the Principal Investigator should contact 
MediBeacon, before the destruction of any records and reports pertaining to the study to ensure 
they no longer need to be retained. 
 
In addition, in accordance with the Clinical Trial Agreement, the Sponsor should be contacted if 
the Principal Investigator plans to leave the investigational site so that appropriate arrangements 
for file custodianship can be made. 
 
The following records must be maintained in designated study administrative files:  
• Clinical protocol and all amendments  
• Signed Investigator Agreement  
• Independent Ethics Committee Approval Letter(s) documenting review and approval of 
all protocols, amendments, IBs, ICFs, subject materials, etc.  
• IEC-approved informed consent(s) (including any revisions)  
• Current Curriculum Vitae for all Investigators and subinvestigators including evidence of 
current medical licensure  
• Financial Disclosure Form for all Investigators 
• Correspondence relating to this study  
• Correspondence with the IEC  
• IEC membership list and/or assurance  
• Investigational site authorized study personnel signature list and delegation of authority 
• Device Instructions for Use  
• Lab certification, including a set of the lab’s normal range for tests performed  


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 74 of 103 
 
• EDC Completion Guidelines  
• Subject Screening & Enrollment Log  
• Site Visit Log (e.g. for Monitor sign-in)  
• Site Training records  
• Investigational Device and Drug Accountability Logs  
• Reports (includes Adverse Event reports and final reports from Investigator and Sponsor) 
• Copy of all EC approved subject-related materials and/or study advertising materials  
 
The following records must be maintained for each subject enrolled in the study:  
• Signed subject consent forms  
• Electronic copy of final completed case reports (to be provided by the sponsor at the end 
of the study) 
• All lab work and testing results  
• Record of any complications, adverse events, device problems and/or malfunctions, with 
supporting documentation  
• Procedure reports, progress notes, physician and/or nursing notes, and subject office files 
• Records pertaining to subject deaths  
 
12 Ethics 
12.1 Independent Ethics Committee (IEC) 
Before initiation of the study at each study site, the protocol, all protocol amendments, 
Investigators Brochure, the ICF, the subject information sheet and any other relevant study 
documentation will be submitted to the appropriate IEC.  Written approval of the study and all 
relevant study information must be obtained before the study site can be initiated or the study 
device is released to the investigator.  Any necessary extensions or renewals of IEC approval 
must be obtained, in particular, for changes to the study such as modification of the protocol, the 
ICF, the written information provided to subjects, and/or other procedures. 
The investigator will report promptly to the IEC any new information that may adversely affect 
the safety of the subjects or the conduct of the study.  The investigator will submit written 
summaries of the study status to the IEC annually, or more frequently if requested by the IEC.  
On completion of the study, the site will notify the IEC that the study has ended. 
12.2 Ethical Conduct of the Study 
The ICH guidelines for current GCP (ICH R2, 2016), The Code of Federal Regulations Title 21 
CFR Parts 812, 11, 50, 54 and 56 and ISO 14155: 2011(E) Clinical Investigation of Medical 
Devices for Human Subjects – Good Clinical Practice, as well as the ethical principles defined 
by the World Medical Association Declaration of Helsinki, and the requirements of national 
device and data protection laws and other applicable regulatory requirements will be followed.  


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 75 of 103 
 
12.3 Subject Information and Consent 
The investigator is responsible for ensuring that no subject undergoes any study related 
examination or activity before that subject has given written informed consent to participate in 
the study.  The written consent must be given by the subject, after detailed information about the 
study has been given and in accordance with any national provisions on the protection of clinical 
study subjects.  The verbal explanation will cover all the elements specified in the written 
information provided for the subject. 
The investigator or designated personnel will inform the subject of the objectives, methods, 
anticipated benefits, and potential risks and inconveniences of the study.  The subject should be 
given every opportunity to ask for clarification of any points he/she does not understand and, if 
necessary, ask for more information.  At the end of the interview, the subject will be given time 
to consider the study, if this is required, or if the subject requests more time.  Subjects and/or 
legally authorized representatives will be required to sign and date the ICF.  After signatures are 
obtained, a copy will be provided to the subject, and a signed ICF will be kept and archived by 
the investigator in the investigator’s study file for possible inspection by regulatory authorities, 
the IEC, or sponsor. 
It should be emphasized to the subject that he/she is at liberty to withdraw from the study at any 
time, without penalty or loss of benefits to which the subject is otherwise entitled.  Subjects who 
refuse to give or who withdraw written informed consent should not be included or continue in 
the study. 
12.4 Financing and Insurance 
This clinical trial will be sponsored by MediBeacon and its conduct will be governed under an 
executed Clinical Trial Agreement that will define the coverage of costs associated with study 
implementation by the trial site. MediBeacon will maintain appropriate clinical trial insurance at 
limits agreed upon in the agreement.  
12.5 Subject Confidentiality  
All personal data collected and processed for the purposes of this study should be managed by 
the investigator and his/her staff with adequate precautions to ensure confidentiality of those 
data, in accordance with applicable national and/or local laws and regulations on personal data 
protection. 
Monitors, auditors, and other authorized agents of the sponsor and/or its designee, the ethics 
committees approving this research, and any other applicable regulatory agency(ies), will be 
granted direct access to the study subjects’ original medical records (including electronic medical 
records) for verification of clinical study procedures and/or data, without violating the 
confidentiality of the subjects to the extent permitted by the law and regulations.  In any 
presentations of the results of this study or in publications, the subjects’ identity will remain 
confidential. 


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MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 76 of 103 
 
12.6 Reporting and Publication, Including Archiving 
Publication of all study results in the form of abstracts, manuscripts, presentations, posters, etc. 
will be developed in accordance with the Clinical Trial Agreement.  
 
 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 77 of 103 
 
13 Post-Dose Procedures by Group and Cohort 
13.1 Group 1 (Cohorts 1 and 2) and Group 2 (Cohorts 3 and 4 subset)  
• Single dose 
• Cohort 1 and 3: healthy to stage 2 CKD: enrolled 50 subjects 
• Cohort 2 and 4: compromised renal function: enrolled 60 subjects 
• 12 hour follow-up 
• Iohexol administration 
• Urine collection 
 
Post-dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 10 minutes (±2 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 15 minutes (±2 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 30 minutes (±5 minutes) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 90 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 78 of 103 
 
• Vital sign collection at 185 minutes (±5 minutes) 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Vital sign collection at 485 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) 
• Vital sign collection at 605 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 720 minutes (±10 minutes) 
• Clinical laboratory (safety labs) draw at 720 minutes (±10 minutes) (chemistry, 
hematology, lipids, and coagulation). The venous catheter may be removed. 
• Vital sign collection at 725 minutes (±5 minutes) 
• 12 lead ECG will be conducted at approximately 740 minutes (±10 minutes) 
• 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.  
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
 
 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 79 of 103 
 
13.2 Post-Dose Procedures: Group 2 (Cohort 4 Extended PK Subgroup only)  
• Single dose 
• Cohort 4: compromised renal function: Enrolled 10 subjects 
• 48 hour follow-up 
• Iohexol administration 
• Urine collection 
 
Post-dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 10 minutes (±2 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 15 minutes (±2 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 30 minutes (±5 minutes) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 90 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 80 of 103 
 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Vital sign collection at 485 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) 
• Vital sign collection at 605 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 720 minutes (±10 minutes) 
• Clinical laboratory (safety labs) draw at 720 minutes (±10 minutes) (chemistry, 
hematology, lipids, and coagulation).  
• Vital sign collection at 725 minutes (±5 minutes) 
• 12 lead ECG will be conducted at approximately 740 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 960 minutes [16 hours] (±30 minutes) 
• Vital sign collection at 965 minutes (±30 minutes) 
o If the ORFM sensors remained attached out to 960 minutes, they may be removed 
after vital signs are collected. Sensors removed after 12 hours but prior to 16 
hours will not be considered a protocol deviation.  
• An ECG will be collected at 1420 minutes (±30 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 1440 minutes [24 hours] (±30 minutes) 
• Vital signs collection (including temperature) at 1445 minutes (±30 minutes)  
• PK draw (6 mL blood) in K2 EDTA tube at 1920 minutes [32 hours] (±30 minute) 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 81 of 103 
 
• Vital signs collection at 1925 minutes (±30 minutes)  
• PK draw (6 mL blood) in K2 EDTA tube at 2400 minutes [40 hours] (±30 minute) 
• Vital signs collection at 2405 minutes (±30 minutes)  
• An ECG will be collected at 2860 minutes (±30 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 2880 minutes [48 hours] (±30 minutes) 
• Vital signs (including temperature) collection at 2885 minutes (±30 minutes)  
• 5 mL urine samples will be collected each time the subject voids. The total volume of 
urine excreted will be recorded until 48 hours post-dose.  
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
 
 
 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 82 of 103 
 
13.3 Post-Dose Procedures: Group 3: Cohort 5  
• Single dose 
• No iohexol 
• No urine collection 
• 8 hour follow-up 
• Healthy to Stage 2 CKD 
• Enrolled 8 subjects 
 
Post MB-102 dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 10 minutes (±2 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 15 minutes (±2 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 30 minutes (±5 minutes) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 90 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 83 of 103 
 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±5 minutes) 
• An ECG will be conducted at 460 minutes (±10 minutes) for all Group 3 subjects with 
the exception of Cohort 7, multiple dose subjects 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Clinical laboratory (safety labs) draw at 480 minutes (±20 minutes) (chemistry, 
hematology, lipids and coagulation). The venous catheter may be removed. 
• Vital sign collection at 485 minutes (±5 minutes) 
• Just after removal of the sensor, additional Mexameter measurements of melanin and 
erythema will be collected at the location where the sensor was attached.  
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
 
 
 
 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 84 of 103 
 
13.4 Post-Dose Procedures: Group 3: SOG  
• Single dose 
• No iohexol 
• No urine collection 
• 12 hour follow-up 
• Normal to stage 2 CKD 
• Up to 27 subjects (3 sets of 9; 18 subjects have been enrolled) 
 
Post MB-102 dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 10 minutes (±2 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 15 minutes (±2 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 30 minutes (±5 minutes) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 90 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 85 of 103 
 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±10 minutes) 
• An ECG will be conducted at 460 minutes (±10 minutes) for all Group 3 subjects with 
the exception of Cohort 7, multiple dose subjects 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Vital sign collection at 485 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) 
• Vital sign collection at 605 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 720 minutes (±10 minutes) 
• Clinical laboratory (safety labs) draw at 720 minutes (±10 minutes) (chemistry, 
hematology, lipids, and coagulation). The venous catheter may be removed. 
• Vital sign collection (includes temperature) at 725 minutes (±10minutes) 
• 12 lead ECG will be conducted at approximately 740 minutes (±10 minutes) 
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
 
 
 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 86 of 103 
 
13.5 Post-Dose Procedures: Group 3: SeVG, Cohort 6 and 7, 7A: Single Dose Subgroup 
• Single Dose 
• 12 hour follow-up 
• Normal and compromised subjects 
• SeVG-1 and SeVG-2: up to 50 subjects  
• Cohort 6: 8 subjects 
• Cohort 7, 7A (single dose): up to 24 subjects 
• A subset of SeVG and Cohort 7 will receive a fixed dose of 7 mL or 130 mg 
 
Post MB-102 dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 10 minutes (±2 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 15 minutes (±2 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 30 minutes (±5 minutes) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 90 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 87 of 103 
 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Vital sign collection at 485 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) 
• Vital sign collection at 605 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 720 minutes (±10 minutes) 
• Clinical laboratory (safety labs) draw at 720 minutes (±10 minutes) (chemistry, 
hematology, lipids, and coagulation). The venous catheter may be removed 
• Vital sign collection (includes temperature) at 725 minutes (±10 minutes) 
• 12 lead ECG will be conducted at approximately 740 minutes (±10 minutes) 
• Just after removal of the sensor, additional Mexameter measurements of melanin and 
erythema will be collected at the location where the sensor was attached. 
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
• Symptom directed physical assessment / exam performed within 2 hours of the 
completion of the dosing day 
 
 


MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 88 of 103 
 
13.6 Post-Dose Procedures: Group 3: Cohort 7,  7A and 7B: Multiple Dose Subgroup 
• Multiple Dose 
• 24 hour – 36 hour follow-up 
• Normal to stage 2 CKD 
• Up to 24 subjects 
• Fixed dose administration (7 mL or 130 mg) 
 
13.6.1 Post First MB-102 Dose Procedures (Cohort 7 and 7A) 
Post first MB-102 dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• For subjects in Cohort 7 and 7A as of protocol Version 12: a PK draw (6 mL) in K2 
EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 


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• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Vital sign collection at 485 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) 
• Vital sign collection at 605 minutes (±10 minutes) 
The ORFM device will notify the clinical team when the monitoring session is complete for the 
study subject. When the device notes that monitoring is complete, the sensor and device should 
remain hooked up to the subject and will continue to collect background fluorescence data for 
the duration of the 2nd dose post-dose monitoring period. No Mexameter measurement will be 
taken at this time.  
At approximately 690 minutes, the subject should be prepared for the 2nd dose administration and 
2nd round of ORFM monitoring.  The following procedures should be followed:  
13.6.2 MB-102 Second Dose Administration (Cohort 7 and 7A) 
• The location for the new sensor will be cleaned, hair clipped (as needed) (the original 
sensor will remain in place) 
• Mexameter readings of melanin and erythema will be measured at the second intended 
site of sensor placement.  
• Prior to dosing, the 2nd device sensor, along with the adhesive clip should be attached to 
the subject and ORFM data acquisition initiated 
• Photographs of the sensor placement may be collected. Photographs will not include any 
identifying features or the subject’s face.  
• PK draw (6 mL blood) in K2 EDTA tube 720 minutes (±10 minutes) post dose 1 (pre-
dose baseline 2) 
• Clinical laboratory safety blood collection at 720 minutes (±10 minutes) post dose 1 
• Vital signs should be collected at 725 minutes (±10 minutes) post dose 1 


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 Version 13.0 
 
 
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• An ECG performed at 730 minutes (±10 minutes) post dose 1 
Once these procedures are complete, the catheter to be used for MB-102 dosing should be 
flushed with saline or a heparin solution and a small volume of blood withdrawn to ensure the 
catheter is patent, and then the catheter should be flushed again.  MB-102 (30 second injection) 
may be administered again followed by a saline flush (30 seconds). Following the 2nd dose 
administration of MB-102, the following procedures will be followed:  
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• For subjects in Cohort 7A: a PK draw (6 mL) in K2 EDTA tube at 60 minutes (±5 
minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 


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 Version 13.0 
 
 
18 June 2021 
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• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) post dose 2 
• Vital sign collection at 485 minutes (±10 minutes) post dose 2 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) post dose 2; the 
venous catheter(s) may be removed 
• Vital sign collection including temperature at 605 minutes (±10 minutes) post dose 2 
• 12 lead ECG will be conducted at approximately 610 minutes (±10 minutes) post dose 2 
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
• Symptom directed physical assessment / exam performed within 2 hours of the 
completion of the dosing day 
The ORFM device will notify the clinical team when the monitoring session is complete for 
the study subject. When the device notes that monitoring is complete, the sensors and device 
should remain hooked up to the subject until after the 10 hour (600 minutes) PK collection is 
completed. At that time, the sensors can be removed from the subject.    
• Just after removal of the sensors, additional Mexameter measurements of melanin and 
erythema will be collected at the location where the sensors were attached. 
13.6.3 Post First MB-102 Dose Procedures (Cohort 7B) 
Post first MB-102 dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 


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Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
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• Vital sign collection at 65 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Vital sign collection at 485 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) 
• Vital sign collection at 605 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 720 minutes (±10 minutes) 
• Vital sign collection at 725 minutes (±10 minutes) 
• An ECG will be performed at 730 minutes (±10 minutes) 
• Sensors and clip may be removed 
• Mexameter measurements collected 


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 Version 13.0 
 
 
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The ORFM device will notify the clinical team when the monitoring session is complete for the 
study subject. When the device notes that monitoring is complete, the sensor and device should 
remain hooked up to the subject and will continue to collect background fluorescence data for 
the duration of the 12 hour follow-up. At this point, the sensors will be removed; Mexameter 
measurements collected; the subject assessed for AEs and allowed to rest for approximately 10-
11 hours.   
13.6.4 MB-102 Second Dose Administration (Cohort 7B) 
• The location for the new sensor will be cleaned, hair clipped (as needed) (the original 
sensor will remain in place) 
• Mexameter readings of melanin and erythema will be measured at the second intended 
site of sensor placement.  
• Prior to dosing, the 2nd device sensor, along with the adhesive clip should be attached to 
the subject and ORFM data acquisition initiated for approximately 20-30 minutes 
• Photographs of the sensor placement may be collected. Photographs will not include any 
identifying features or the subject’s face.  
• PK draw (6 mL blood) in K2 EDTA tube 1440 minutes [24 hours] (±10 minutes) post 
dose 1 (pre-dose baseline 2) 
• Clinical laboratory safety blood collection at 1440 minutes (±10 minutes) post dose 1 
• Vital signs should be collected at 1445 minutes (±10 minutes) post dose 1 
• An ECG performed at 1450 minutes (±10 minutes) post dose 1 
Once these procedures are complete, MB-102 (30 second injection) may be administered via 
direct IV injection followed by a saline flush (30 seconds). For Cohorts 7A and 7B, the second 
dose will be administered in the same arm but a different vein than the initial injection. 
Following the 2nd dose administration of MB-102, the following procedures will be followed:  
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 


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Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
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• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) post dose 2 
• Vital sign collection at 485 minutes (±10 minutes) post dose 2 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) post dose 2; the 
venous catheter(s) may be removed 
• Vital sign collection including temperature at 605 minutes (±10 minutes) post dose 2 
• 12 lead ECG will be conducted at approximately 610 minutes (±10 minutes) post dose 2 
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
The ORFM device will notify the clinical team when the monitoring session is complete for 
the study subject.  When the device notes that monitoring is complete, the sensors and device 
should remain hooked up to the subject until after the 10 hour (600 minutes) PK collection is 


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Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
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completed. At that time, the sensors can be removed from the subject.   Just after removal of 
the sensors, additional Mexameter measurements of melanin and erythema will be collected 
at the location where the sensors were attached. 
13.7 Post-Dose Procedures: Group 3: Cohort 8 and 8A  
• Single dose 
• Renal compromised subjects 
• 48 hour follow-up 
• Up to 16 subjects 
• Fixed dose administration (7 mL or 130 mg) 
 
Post-dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 10 minutes (±2 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 15 minutes (±2 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 30 minutes (±5 minutes) 
• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 90 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 


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 Version 13.0 
 
 
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• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Vital sign collection at 485 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) 
• Vital sign collection at 605 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 720 minutes (±10 minutes) 
• Clinical laboratory (safety labs) draw at 720 minutes (±10 minutes) (chemistry, 
hematology, lipids, and coagulation).  
• Vital sign collection at 725 minutes (±10 minutes) 
• 12 lead ECG will be conducted at approximately 740 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 960 minutes [16 hours] (±30 minutes) 
• Vital sign collection at 965 minutes (±30 minutes) 
• An ECG will be collected at 1420 minutes (±30 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 1440 minutes [24 hours] (±30 minutes) 
• Vital signs collection (including temperature) at 1445 minutes (±30 minutes)  
• PK draw (6 mL blood) in K2 EDTA tube at 1920 minutes [32 hours] (±30 minute) 


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 Version 13.0 
 
 
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• Vital signs collection at 1925 minutes (±30 minutes)  
• PK draw (6 mL blood) in K2 EDTA tube at 2400 minutes [40 hours] (±30 minute) 
• Vital signs collection at 2405 minutes (±30 minutes)  
• An ECG will be collected at 2860 minutes (±30 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 2880 minutes [48 hours] (±30 minutes).  The 
venous catheter may be removed. 
• Vital signs (including temperature) collection at 2885 minutes (±30 minutes)  
• Just after removal of the sensor, additional Mexameter measurements of melanin and 
erythema will be collected at the location where the sensor was attached. 
• Symptom directed physical assessment / exam performed within 2 hours of the 
completion of the dosing day 
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
13.8 Post-Dose Procedures: Group 3: Cohort 8B  
• Single dose 
• Renal compromised subjects 
• 24 hour follow-up 
• Up to 8 subjects 
• Fixed dose administration (7 mL or 130 mg) 
 
Post-dose study procedures will be performed at the following timepoints: 
• PK draw (6 mL blood) in K2 EDTA tube at 5 minutes (±1 minute) 
• Vital sign collection at 6 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 10 minutes (±2 minute) 
• Vital sign collection at 11 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 15 minutes (±2 minute) 
• Vital sign collection at 16 minutes (±1 minute) 
• PK draw (6 mL blood) in K2 EDTA tube at 30 minutes (±5 minutes) 


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 Version 13.0 
 
 
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• Vital sign collection at 35 minutes (±5 minutes) 
• An ECG will be conducted at 55 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 60 minutes (±5 minutes) 
• Vital sign collection at 65 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 90 minutes (±5 minutes) 
• Vital sign collection at 95 minutes (±5 minutes) 
• An ECG will be conducted at 115 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 120 minutes (±5 minutes) 
• Vital sign collection at 125 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 180 minutes (±5 minutes) 
• Vital sign collection at 185 minutes (±5 minutes) 
• An ECG will be conducted at 235 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 240 minutes (±5 minutes) 
• Vital sign collection at 245 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 300 minutes (±5 minutes) 
• Vital sign collection at 305 minutes (±5 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 360 minutes (±10 minutes) 
• Vital sign collection at 365 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 480 minutes (±10 minutes) 
• Vital sign collection at 485 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 600 minutes (±10 minutes) 
• Vital sign collection at 605 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 720 minutes (±10 minutes) 


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 Version 13.0 
 
 
18 June 2021 
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• Clinical laboratory (safety labs) draw at 720 minutes (±10 minutes) (chemistry, 
hematology, lipids, and coagulation).  
• Vital sign collection at 725 minutes (±10 minutes) 
• 12 lead ECG will be conducted at approximately 740 minutes (±10 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 960 minutes [16 hours] (±30 minutes) 
• Vital sign collection at 965 minutes (±30 minutes) 
• An ECG will be collected at 1420 minutes (±30 minutes) 
• PK draw (6 mL blood) in K2 EDTA tube at 1440 minutes [24 hours] (±30 minutes) 
• Vital signs collection (including temperature) at 1445 minutes (±30 minutes)  
• Just after removal of the sensor, additional Mexameter measurements of melanin and 
erythema will be collected at the location where the sensor was attached. 
• Symptom directed physical assessment / exam performed within 2 hours of the 
completion of the dosing day 
• Adverse events will be collected based on subject and medical team observations 
throughout the post-dose assessment period 
 
 


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 Version 13.0 
 
 
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14 References 
Agarwal R. Ambulatory GFR measurement with cold iothalamate in adults with chronic kidney 
disease. Am J Kidney Dis. 2003 Apr; 41(4): 752-9. 
 
Endre ZH, Pickering JW, Walker RJ.  Clearance and beyond: the complementary roles of GFR 
measurement and injury biomarkers in acute kidney injury (AKI). Am J Physiol Renal Physiol 
2011 301: F697-F707. 
 
Erley CM, Bader BD, Berger ED, et al. Plasma clearance of iodine contrast media as a measure 
of glomerular filtration rate in critically ill patients. Crit Care Med. 2001 Aug; 29(8):1544-50. 
 
Fitzpatrick TB. Soleil et peau [Sun and skin]. Journal de Médecine Esthétique. 1975; 2:33-34 
 
Kidney Disease Statistics for the United States. 
http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/index.aspx#13 
 
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers 
P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology 
Collaboration). A New Equation to Estimate Glomerular Filtration Rate. Ann Intern Med. 2009 
May 5;150(9):604-12. 
 
National Institutes of Health Web Site (Bethesda MD, 08 October 2008), “Annual report targets 
chronic kidney disease in the United States,” http://www.nih.gov/news/health/oct2008/niddk-
08.htm 
 
Nilsson-Ehle P:  Iohexol clearance for the determination of glomerular filtration rate: 15 years 
experience in clinical practice, eJIFCC vol 13 no 2:  
http://www.ifcc.org/ejifcc/vol13no2/1301200105.htm 
 
Rabito C, Halpern EF, Scott J and N Tolkoff-Rubin. Accurate, fast, and convenient measurement 
of glomerular filtration rate in potential renal transplant donors. Transplantation 2010; 90: 510–
517).  
 
Stevens, LA and Levey, AS. Measured GFR as a Confirmatory Test for Estimated GFR. 2009. J. 
Am Soc Nephrol 20: 2305-2313.  
 
Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function--measured and estimated 
glomerular filtration rate. N Engl J Med. 2006 Jun 8;354 (23):2473-83. 
 
Verhave JC, Fesler P, Ribstein J, du Cailar G, Mimran A. Estimation of renal function in 
subjects with normal serum creatinine levels: influence of age and body mass index. Am J 
Kidney Dis. 2005 Aug; 46(2): 233-41. 
 


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 Version 13.0 
 
 
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Appendix A Fitzpatrick Scale  
 
 
 
Source: Fitzpatrick, 1975 
 
 
 


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Appendix B: Package Insert for Omnipaque™ 300 
 




2.   Inform your physician if you are diabetic or if you have multiple myeloma, pheochromocytoma,
homozygous sickle cell disease or known thyroid disorder (see WARNINGS).
3.   Inform your physician if you are allergic to any drugs, food, or if you had any reactions to
previous injections of dyes used for x-ray procedures (see PRECAUTIONS—General).
4.   Inform your physician about any other medications you are currently taking, including non-
prescription drugs, before you are administered this drug.
Drug Interactions
Drugs which lower seizure threshold, especially phenothiazine derivatives including those used for
their antihistaminic or antinauseant properties, are not recommended for use with OMNIPAQUE.
Others include monoamine oxidase (MAO) inhibitors, tricyclic antidepressants, CNS stimulants,
psychoactive drugs described as analeptics, major tranquilizers, or antipsychotic drugs. Such med-
ications should be discontinued at least 48 hours before myelography, should not be used for the
control of nausea or vomiting during or after myelography, and should not be resumed for at least
24 hours postprocedure. In nonelective procedures in patients on these drugs, consider prophylactic
use of anticonvulsants.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term animal studies have been performed to evaluate carcinogenic potential, mutagenesis,
or whether OMNIPAQUE can affect fertility in men or women.
Pregnancy Category B
Reproduction studies have been performed in rats and rabbits with up to 100 times the recom-
mended human dose. No evidence of impaired fertility or harm to the fetus has been demonstrated
due to OMNIPAQUE. There are, however, no studies in pregnant women. Because animal reproduc-
tion studies are not always predictive of human response, this drug should be used during
pregnancy only if clearly needed.
Nursing Mothers
It is not known to what extent iohexol is excreted in human milk. However, many injectable contrast
agents are excreted unchanged in human milk. Although it has not been established that serious
adverse reactions occur in nursing infants, caution should be exercised when intravascular contrast
media are administered to nursing women. Bottle feedings may be substituted for breast feedings
for 24 hours following administration of OMNIPAQUE.
Pediatric Use
Pediatric patients at higher risk of experiencing adverse events during contrast medium administra-
tion may include those having asthma, a sensitivity to medication and/or allergens, congestive
heart failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age.
ADVERSE REACTIONS—Intrathecal
The most frequently reported adverse reactions with OMNIPAQUE are headache, mild to moderate
pain including backache, neckache and stiffness, nausea, and vomiting. These reactions usually
occur 1 to 10 hours after injection, and almost all occur within 24 hours. They are usually mild to
moderate in degree, lasting for a few hours, and usually disappearing within 24 hours. Rarely,
headaches may be severe or persist for days. Headache is often accompanied by nausea and
vomiting and tends to be more frequent and persistent in patients not optimally hydrated.
Transient alterations in vital signs may occur and their significance must be assessed on an
individual basis. Those reactions reported in clinical studies with OMNIPAQUE are listed below in
decreasing order of occurrence, based on clinical studies of 1531 patients.
Headaches: The most frequently occurring adverse reaction following myelography has been head-
ache, with an incidence of approximately 18%. Headache may be caused by either a direct effect of
the contrast medium or by CSF leakage at the dural puncture site. However, in managing the patient,
it is considered more important to minimize intracranial entry of contrast medium by postural 
management than attempting to control possible CSF leakage (see PATIENT MANAGEMENT).
Pain: Mild to moderate pain including backache, neckache and stiffness, and neuralgia occurred
following injection with an incidence of about 8%.
Nausea and Vomiting: Nausea was reported with an incidence of about 6%, and vomiting about 3%
(see PATIENT MANAGEMENT). Maintaining normal hydration is very important. The use of 
phenothiazine antinauseants is not recommended. (See WARNINGS—General.) Reassurance to the
patient that the nausea will clear usually is all that is required.
Dizziness: Transient dizziness was reported in about 2% of the patients.
Other Reactions: Other reactions occurring with an individual incidence of less than 0.1% included:
feeling of heaviness, hypotension, hypertonia, sensation of heat, sweating, vertigo, loss of appetite,
drowsiness, hypertension, photophobia, tinnitus, neuralgia, paresthesia, difficulty in micturition, and
neurological changes. All were transient and mild with no clinical sequelae.
Pediatrics
In controlled clinical trials involving 152 patients for pediatric myelography by lumbar puncture,
adverse events following the use of OMNIPAQUE 180 were generally less frequent than with adults.
Headache:
9%
Vomiting:
6%
Backache:
1.3%
Other Reactions: Other reactions occurring with an individual incidence of less than 0.7% included:
fever, hives, stomachache, visual hallucination, and neurological changes. All were transient and
mild with no clinical sequelae.
General Adverse Reactions to Contrast Media
Physicians should remain alert for the occurrence of adverse effects in addition to those discussed
above, particularly the following reactions which have been reported in the literature for other
nonionic, water-soluble myelographic media, and rarely with iohexol. These have included, but are
not limited to, convulsion, aseptic and bacterial meningitis, and CNS and other neurological
disturbances.
An aseptic meningitis syndrome has been reported rarely (less than 0.01%). It was usually preceded
by pronounced headaches, nausea and vomiting. Onset usually occurred about 12 to 18 hours post-
procedure. Prominent features were meningismus, fever, sometimes with oculomotor signs and
mental confusion. Lumbar puncture revealed a high white cell count, high protein content often with
a low glucose level and with absence of organisms. The condition usually started to clear
spontaneously about 10 hours after onset, with complete recovery over 2 to 3 days.
Allergy or Idiosyncrasy: Chills, fever, profuse diaphoresis, pruritus, urticaria, nasal congestion, 
dyspnea, and a case of Guillain-Barre syndrome.
CNS Irritation: Mild and transitory perceptual aberrations such as hallucinations, depersonalization,
amnesia, hostility, amblyopia, diplopia, photophobia, psychosis, insomnia, anxiety, depression,
hyperesthesia, visual or auditory or speech disturbances, confusion and disorientation. In addition,
malaise, weakness, convulsion, EEG changes, meningismus, hyperreflexia or areflexia, hypertonia or
flaccidity, hemiplegia, paralysis, quadriplegia, restlessness, tremor, echoacousia, echolalia, asterixis,
cerebral hemorrhage, and dysphasia have occurred.
Profound mental disturbances have also rarely been reported. They have usually consisted of
various forms and degrees of aphasia, mental confusion, or disorientation. The onset is usually at 8
to 10 hours and lasts for about 24 hours, without aftereffects. However, occasionally they have been
manifest as apprehension, agitation, or progressive withdrawal in several instances to the point of
somnolence, stupor, and coma. In a few cases these have been accompanied by transitory hearing
loss or other auditory symptoms and visual disturbances (believed subjective or delusional),
including unilateral or bilateral loss of vision which may last for hours. In one case, persistent
cortical loss of vision has been reported in association with convulsions. Ventricular block has been
reported; amnesia of varying degrees may be present for the reaction event.
Rarely, persistent though transitory weakness in the leg or ocular muscles has been reported.
Peripheral neuropathies have been rare and transitory. They include sensory and/or motor or nerve
root disturbances, myelitis, persistent leg muscle pain or weakness, 6th nerve palsy, or cauda
equina syndrome. Muscle cramps, fasciculation or myoclonia, spinal convulsion, or spasticity is
unusual and has responded promptly to a small intravenous dose of diazepam.
In general, the reactions which are known to occur upon parenteral administration of iodinated
contrast agents are possible with any nonionic agent. Approximately 95 percent of adverse
reactions accompanying the use of water-soluble contrast agents are mild to moderate in degree.
However, severe, life-threatening, anaphylactoid and fatal reactions, mostly of cardiovascular origin
and central nervous system origin, have occurred.
Adverse reactions to injectable contrast media fall into two categories: chemotoxic reactions and
idiosyncratic reactions.
Chemotoxic reactions result from the physicochemical properties of the contrast media, the dose,
and speed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by
the contrast medium are included in this category.
Idiosyncratic reactions include all other reactions. They occur more frequently in patients 20 to 40
years old. Idiosyncratic reactions may or may not be dependent on the amount of dose injected, the
speed of injection, and the radiographic procedure. Idiosyncratic reactions are subdivided into
minor, intermediate, and severe. The minor reactions are self-limited and of short duration; the
severe reactions are life-threatening and treatment is urgent and mandatory.
The reported incidence of adverse reactions to contrast media in patients with a history of allergy is
twice that of the general population. Patients with a history of previous reactions to a contrast
medium are three times more susceptible than other patients. However, sensitivity to contrast
media does not appear to increase with repeated examinations.
Most adverse reactions to injectable contrast media appear within 1 to 3 minutes after the start of
injection, but delayed reactions may occur.
OVERDOSAGE
Clinical consequences of overdosage with OMNIPAQUE have not been reported. However, based on
experience with other nonionic myelographic media, physicians should be alert to a potential
increase in frequency and severity of CNS-mediated reactions. Even use of a recommended dose can
produce effects tantamount to overdosage, if incorrect management of the patient during or im-
mediately following the procedure permits inadvertent early intracranial entry of a large portion of
the medium.
The intracisternal LD50 value of OMNIPAQUE (in grams of iodine per kilogram body weight) is greater
than 2.0 in mice.
DOSAGE AND ADMINISTRATION — Intrathecal
The volume and concentration of OMNIPAQUE 180, OMNIPAQUE 240, or OMNIPAQUE 300 to be
administered will depend on the degree and extent of contrast required in the area(s) under exami-
nation and on the equipment and technique employed.
OMNIPAQUE 180 at a concentration of 180 mgI/mL, OMNIPAQUE 240 at a concentration of 240
mgI/mL, or OMNIPAQUE 300 at a concentration of 300 mgI/mL is recommended for the examination
of the lumbar, thoracic, and cervical regions in adults by lumbar or direct cervical injection and is
slightly hypertonic to CSF.
OMNIPAQUE 180 at a concentration of 180 mgI/mL is recommended for the examination of the
lumbar, thoracic, and cervical regions in children by lumbar injection and is slightly hypertonic to
CSF.
A total dose of 3060 mg iodine or a concentration of 300 mgI/mL should not be exceeded in adults
and a total dose of 2700 mg iodine or a concentration of 180 mgI/mL should not be exceeded in
children in a single myelographic examination. This is based on clinical trial evaluation to date. As in
all diagnostic procedures, the minimum volume and dose to produce adequate visualization should
be used. Most procedures do not require either maximum dose or concentration.
Anesthesia is not necessary. Premedication sedatives or tranquilizers are usually not needed (see
PRECAUTIONS). Patients should be well hydrated prior to and following contrast administration.
Seizure-prone patients should be maintained on anticonvulsant medication.
Many radiopaque contrast agents are incompatible in vitro with some antihistamines and many
other drugs; therefore, concurrent drugs should not be physically admixed with contrast agents.
Rate of Injection: To avoid excessive mixing with CSF and consequent dilution of contrast, injection
should be made slowly over 1 to 2 minutes.
Depending on the estimated volume of contrast medium which may be required for the procedure
a small amount of CSF may be removed to minimize distention of the subarachnoid spaces.
The lumbar or cervical puncture needle may be removed immediately following injection since it is
not necessary to remove OMNIPAQUE after injection into the subarachnoid space.
Adults: The usual recommended total doses for use in lumbar, thoracic, cervical, and total columnar
myelography in adults are 1.2 gI to 3.06 gI as follows:
Concentration
Volume
Dose
Procedure
Formulations
(mgI/mL)
(mL)
(gI)
Lumbar
Myelography
OMNIPAQUE 180
180
10-17
1.8-3.06
(via lumbar
OMNIPAQUE 240
240
7-12.5
1.7-3.0
injection)
Thoracic
Myelography
OMNIPAQUE 240
240
6-12.5
1.7-3.0
(via lumbar
OMNIPAQUE 300
300
6-10
1.8-3.0
or cervical
injection)
Cervical
Myelography
OMNIPAQUE 240
240
6-12.5
1.4-3.0
(via lumbar
OMNIPAQUE 300
300
6-10
1.8-3.0
injection)
Cervical
OMNIPAQUE 180
180
7-10
1.3-1.8
Myelography
OMNIPAQUE 240
240
6-12.5
1.4-3.0
(via C1-2
OMNIPAQUE 300
300
4-10
1.2-3.0
injection)
Total Columnar
Myelography
OMNIPAQUE 240
240
6-12.5
1.4-3.0
(via lumbar
OMNIPAQUE 300
300
6-10
1.8-3.0
injection)
Pediatrics: The usual recommended total doses for lumbar, thoracic, cervical, and/or total columnar
myelography by lumbar puncture in children are 0.36 gI to 2.7 gI (see table below). Actual volumes
administered depend largely on patient age and the following guidelines are recommended.
Conc.
Volume
Dose
Age
(mgI/mL)
(mL)
(gI)
0 to < 3 mos.
180
2-4
0.36-0.72
3 to < 36 mos.
180
4-8
0.72-1.44
3 to < 7 yrs.
180
5-10
0.9-1.8
7 to < 13 yrs.
180
5-12
0.9-2.16
13 to 18 yrs.
180
6-15
1.08-2.7
Withdrawal of contrast agents from their containers should be accomplished under aseptic 
conditions with sterile syringes. Spinal puncture must always be performed under sterile conditions.
Parenteral products should be inspected visually for particulate matter or discoloration prior
to administration. If particulate matter or discoloration is present, do not use.
Repeat Procedures: If in the clinical judgment of the physician sequential or repeat examinations
are required, a suitable interval of time between administrations should be observed to allow for
normal clearance of the drug from the body. An interval of at least 48 hours should be allowed before
repeat examination; however, whenever possible, 5 to 7 days is recommended.
2
OMNIPAQUE (iohexol) Injection 


PATIENT MANAGEMENT—Intrathecal
Suggestions for Usual Patient Management
Good patient management should be exercised at all times to minimize the potential for procedu-
rally related complications.
Preprocedure
• Discontinuance of neuroleptic drugs (including phenothiazines, eg, chlorpromazine,
prochlorperazine, and promethazine) at least 48 hours beforehand should be considered.
• Maintain normal diet up to 2 hours before procedure.
• Ensure hydration-fluids up to procedure.
During Procedure
• Use minimum dose and concentration required for satisfactory contrast (see DOSAGE AND
ADMINISTRATION).
• In all positioning techniques keep the patient’s head elevated above highest level of spine.
• Do not lower head of table more than 15° in moving contrast medium cranially.
• In patients with excessive lordosis, consider lateral position for injection and movement of the
medium cephalad.
• Inject slowly (over 1 to 2 minutes) to avoid excessive mixing.
• To maintain as a bolus, move medium to distal area very slowly. Use fluoroscopic monitoring.
• Avoid intracranial entry of a bolus.
• Avoid early and high cephalad dispersion of the medium.
• Avoid abrupt or active patient movement to minimize excessive mixing of medium with CSF.
Instruct patient to remain passive. Move patient slowly and only as necessary.
Postprocedure
• Raise head of stretcher to at least 30° before moving patient onto it.
• Movement onto and off the stretcher should be done slowly with the patient completely
passive, maintaining head-up position.
• Before moving patient onto bed, raise head of bed 30° to 45°.
• Advise patient to remain still in bed, in a sitting or semisitting position, especially in the first
few hours.
• Maintain close observation for at least 12 hours after myelogram.
• Obtain visitors’ cooperation in keeping the patient quiet and in head-up position, especially in
first few hours.
• Encourage oral fluids. Diet as tolerated.
• If nausea or vomiting occurs, do not use phenothiazine antinauseants. Persistent nausea and
vomiting will result in dehydration. Therefore, prompt consideration of replacement by
intravenous fluids is recommended.
Alternative Postprocedure Method
• Recent evidence with nonionic, water-soluble contrast media suggests that maintaining the
patient postmyelography in an upright position (via wheelchair or ambulation) may help
minimize adverse effects. The upright position may help to delay upward dispersion of the
medium and to maximize the spinal arachnoid absorption.
SECTION II
CLINICAL PHARMACOLOGY—Intravascular
Following intravascular injection, iohexol is distributed in the extracellular fluid compartment and is
excreted unchanged by glomerular filtration. It will opacify those vessels in the path of flow of the
contrast medium permitting radiographic visualization of the internal structures until significant
hemodilution occurs.
Approximately 90% or more of the injected dose is excreted within the first 24 hours, with the peak
urine concentrations occurring in the first hour after administration. Plasma and urine iohexol levels
indicate that the iohexol body clearance is due primarily to renal clearance. An increase in the dose
from 500 mgI/kg to 1500 mgI/kg does not significantly alter the clearance of the drug. The following
pharmacokinetic values were observed following the intravenous administration of iohexol (be-
tween 500 mgI/kg to 1500 mgI/kg) to 16 adult human subjects: renal clearance—120 (86-162)
mL/min; total body clearance—131 (98-165) mL/min; and volume of distribution—165 (108-219)
mL/kg.
Renal accumulation is sufficiently rapid that the period of maximal opacification of the renal
passages may begin as early as 1 minute after intravenous injection. Urograms become apparent in
about 1 to 3 minutes with optimal contrast occurring between 5 to 15 minutes. In nephropathic
conditions, particularly when excretory capacity has been altered, the rate of excretion may vary
unpredictably, and opacification may be delayed after injection. Severe renal impairment may result
in a lack of diagnostic opacification of the collecting system and, depending on the degree of renal
impairment, prolonged plasma iohexol levels may be anticipated. In these patients, as well as in
infants with immature kidneys, the route of excretion through the gallbladder and into the small
intestine may increase.
Iohexol displays a low affinity for serum or plasma proteins and is poorly bound to serum albumin.
No significant metabolism, deiodination or biotransformation occurs.
OMNIPAQUE probably crosses the placental barrier in humans by simple diffusion. It is not known to
what extent iohexol is excreted in human milk.
Animal studies indicate that iohexol does not cross an intact blood-brain barrier to any significant
extent following intravascular administration.
OMNIPAQUE enhances computed tomographic imaging through augmentation of radiographic
efficiency. The degree of density enhancement is directly related to the iodine content in an admini-
stered dose; peak iodine blood levels occur immediately following rapid intravenous injection. Blood
levels fall rapidly within 5 to 10 minutes and the vascular compartment half-life is approximately 20
minutes. This can be accounted for by the dilution in the vascular and extravascular fluid
compartments which causes an initial sharp fall in plasma concentration. Equilibration with the
extracellular compartments is reached in about ten minutes; thereafter, the fall becomes
exponential.
The pharmacokinetics of iohexol in both normal and abnormal tissue have been shown to be
variable. Contrast enhancement appears to be greatest immediately after bolus administration (15
seconds to 120 seconds). Thus, greatest enhancement may be detected by a series of consecutive
two-to-three second scans performed within 30 to 90 seconds after injection (ie, dynamic computed
tomographic imaging). Utilization of a continuous scanning technique (ie, dynamic CT scanning) may
improve enhancement and diagnostic assessment of tumor and other lesions such as abscess,
occasionally revealing unsuspected or more extensive disease. For example, a cyst may be
distinguished from a vascularized solid lesion when precontrast and enhanced scans are compared;
the nonperfused mass shows unchanged x-ray absorption (CT number). A vascularized lesion is
characterized by an increase in CT number in the few minutes after a bolus of intravascular contrast
agent; it may be malignant, benign, or normal tissue, but would probably not be a cyst, hematoma,
or other nonvascular lesion.
Because unenhanced scanning may provide adequate diagnostic information in the individual
patient, the decision to employ contrast enhancement, which may be associated with risk and
increased radiation exposure, should be based upon a careful evaluation of clinical, other radiologi-
cal, and unenhanced CT findings.
CT SCANNING OF THE HEAD
In contrast enhanced computed tomographic head imaging, OMNIPAQUE does not accumulate in
normal brain tissue due to the presence of the normal blood-brain barrier. The increase in x-ray
absorption in normal brain is due to the presence of contrast agent within the blood pool. A break in
the blood-brain barrier such as occurs in malignant tumors of the brain allows for the accumulation
of contrast medium within the interstitial tissue of the tumor. Adjacent normal brain tissue does not
contain the contrast medium.
Maximum contrast enhancement in tissue frequently occurs after peak blood iodine levels are
reached. A delay in maximum contrast enhancement can occur. Diagnostic contrast enhanced
images of the brain have been obtained up to 1 hour after intravenous bolus administration. This
delay suggests that radiographic contrast enhancement is at least in part dependent on the
accumulation of iodine containing medium within the lesion and outside the blood pool, although
the mechanism by which this occurs is not clear. The radiographic enhancement of nontumoral
lesions, such as arteriovenous malformations and aneurysms, is probably dependent on the iodine
content of the circulating blood pool.
In patients where the blood-brain barrier is known or suspected to be disrupted, the use of any
radiographic contrast medium must be assessed on an individual risk to benefit basis. However,
compared to ionic media, nonionic media are less toxic to the central nervous system.
CT SCANNING OF THE BODY
In contrast enhanced computed tomographic body imaging (nonneural tissue), OMNIPAQUE diffuses
rapidly from the vascular into the extravascular space. Increase in x-ray absorption is related to
blood flow, concentration of the contrast medium, and extraction of the contrast medium by
interstitial tissue of tumors since no barrier exists. Contrast enhancement is thus due to the relative
differences in extravascular diffusion between normal and abnormal tissue, quite different from that
in the brain.
INDICATIONS AND USAGE, GENERAL—Intravascular
OMNIPAQUE 350 is indicated in adults for angiocardiography (ventriculography, selective coronary
arteriography), aortography including studies of the aortic root, aortic arch, ascending aorta,
abdominal aorta and its branches, contrast enhancement for computed tomographic head and
body imaging, intravenous digital subtraction angiography of the head, neck, abdominal, renal and
peripheral vessels, peripheral arteriography, and excretory urography.
OMNIPAQUE 350 is indicated in children for angiocardiography (ventriculography, pulmonary
arteriography, and venography; studies of the collateral arteries and aortography, including the
aortic root, aortic arch, ascending and descending aorta).
OMNIPAQUE 300 is indicated in adults for aortography including studies of the aortic arch,
abdominal aorta and its branches, contrast enhancement for computed tomographic head and
body imaging, cerebral arteriography, peripheral venography (phlebography), and excretory urogra-
phy.
OMNIPAQUE 300 is indicated in children for angiocardiography (ventriculography), excretory
urography, and contrast enhancement for computed tomographic head imaging.
OMNIPAQUE 240 is indicated in adults for contrast enhancement for computed tomographic head
imaging and peripheral venography (phlebography).
OMNIPAQUE 140 is indicated in adults for intra-arterial digital subtraction angiography of the head,
neck, abdominal, renal and peripheral vessels.
OMNIPAQUE 240 is indicated in children for contrast enhancement for computed tomographic head
imaging.
CONTRAINDICATIONS
OMNIPAQUE should not be administered to patients with a known hypersensitivity to iohexol.
WARNINGS—General
Nonionic iodinated contrast media inhibit blood coagulation, in vitro, less than ionic contrast media.
Clotting has been reported when blood remains in contact with syringes containing nonionic
contrast media.
Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been
reported during angiographic procedures with both ionic and nonionic contrast media. Therefore,
meticulous intravascular administration technique is necessary, particularly during angiographic
procedures, to minimize thromboembolic events. Numerous factors, including length of procedure,
catheter and syringe material, underlying disease state, and concomitant medications, may
contribute to the development of thromboembolic events. For these reasons, meticulous angiogra-
phic techniques are recommended including close attention to guidewire and catheter manipula-
tion, use of manifold systems and/or three-way stopcocks, frequent catheter flushing with hepar-
inized saline solutions and minimizing the length of the procedure. The use of plastic syringes in
place of glass syringes has been reported to decrease but not eliminate the likelihood of in vitro
clotting.
OMNIPAQUE should be used with extreme care in patients with severe functional disturbances of the
liver and kidneys, severe thyrotoxicosis, or myelomatosis. Diabetics with a serum creatinine level
above 3 mg/dL should not be examined unless the possible benefits of the examination clearly
outweigh the additional risk. OMNIPAQUE is not recommended for use in patients with anuria.
Radiopaque contrast agents are potentially hazardous in patients with multiple myeloma or other
paraproteinemia, particularly in those with therapeutically resistant anuria. Although neither the
contrast agent nor dehydration has separately proven to be the cause of anuria in myeloma, it has
been speculated that the combination of both may be causative factors. The risk in myelomatous
patients is not a contraindication; however, special precautions are necessary. Partial dehydration
in the preparation of these patients prior to injection is not recommended since this may predispose
the patient to precipitation of the myeloma protein in the renal tubules. No form of therapy, including
dialysis, has been successful in reversing the effect. Myeloma, which occurs most commonly in
persons over age 40, should be considered before instituting intravascular administration of
contrast agents.
Ionic contrast media, when injected intravenously or intra-arterially, may promote sickling in 
individuals who are homozygous for sickle cell disease.
Administration of radiopaque materials to patients known or suspected of having pheochromocy-
toma should be performed with extreme caution. If, in the opinion of the physician, the possible
benefits of such procedures outweigh the considered risks, the procedures may be performed;
however, the amount of radiopaque medium injected should be kept to an absolute minimum. The
patient’s blood pressure should be assessed throughout the procedure and measures for the
treatment of hypertensive crisis should be readily available.
Reports of thyroid storm following the use of iodinated, ionic radiopaque contrast media in patients
with hyperthyroidism or with an autonomously functioning thyroid nodule suggest that this
additional risk be evaluated in such patients before use of any contrast medium.
Urography should be performed with caution in patients with severely impaired renal function and
patients with combined renal and hepatic disease.
PRECAUTIONS—General
Diagnostic procedures which involve the use of radiopaque diagnostic agents should be carried out
under the direction of personnel with the prerequisite training and with a thorough knowledge of the
particular procedure to be performed. Appropriate facilities should be available for coping with any
complication of the procedure, as well as for emergency treatment of severe reactions to the
contrast agent itself. After parenteral administration of a radiopaque agent, competent personnel
and emergency facilities should be available for at least 30 to 60 minutes since severe delayed
reactions have occurred (see ADVERSE REACTIONS: Intravascular—General).
Preparatory dehydration is dangerous and may contribute to acute renal failure in patients with
advanced vascular disease, diabetic patients, and in susceptible nondiabetic patients (often elderly
with preexisting renal disease), infants and small children. Dehydration in these patients seems to be
enhanced by the osmotic diuretic action of urographic agents. It is believed that overnight fluid
restriction prior to excretory urography generally does not provide better visualization in normal
patients. Patients should be well hydrated prior to and following administration of any contrast
medium, including iohexol.
Acute renal failure has been reported in diabetic patients with diabetic nephropathy and in
susceptible non-diabetic patients (often elderly with preexisting renal disease) following excretory
3
OMNIPAQUE (iohexol) Injection 


Respiratory System: Dyspnea, rhinitis, coughing, and laryngitis, with an individual incidence of 0.2%
or less.
Gastrointestinal System: Nausea (2%) and vomiting (0.7%). Others including diarrhea, dyspepsia,
cramp, and dry mouth were reported, with an individual incidence of less than 0.1%.
Skin and Appendages: Urticaria (0.3%), purpura (0.1%), abscess (0.1%), and pruritus (0.1%).
Individual adverse reactions which occurred to a significantly greater extent for a specific procedure
are listed under that indication.
Pediatrics
In controlled clinical trials involving 391 patients for pediatric angiocardiography, urography, and
contrast enhanced computed tomographic head imaging, adverse reactions following the use of
OMNIPAQUE 240, OMNIPAQUE 300, and OMNIPAQUE 350 were generally less frequent than with
adults.
Cardiovascular System: Ventricular tachycardia (0.5%), 2:1 heart block (0.5%), hypertension (0.3%),
and anemia (0.3%).
Nervous System: Pain (0.8%), fever (0.5%), taste abnormality (0.5%), and convulsion (0.3%).
Respiratory System: Congestion (0.3%) and apnea (0.3%).
Gastrointestinal System: Nausea (1%), hypoglycemia (0.3%), and vomiting (2%).
Skin and Appendages: Rash (0.3%).
General Adverse Reactions to Contrast Media
Physicians should remain alert for the occurrence of adverse effects in addition to those discussed
above.
The following reactions have been reported after administration of other intravascular iodinated
contrast media, and rarely with iohexol. Reactions due to technique: hematomas and ecchymoses.
Hemodynamic reactions: vein cramp and thrombophlebitis following intravenous injection. Cardio-
vascular reactions: rare cases of cardiac arrhythmias, reflex tachycardia, chest pain, cyanosis,
hypertension, hypotension, peripheral vasodilatation, shock, and cardiac arrest. Renal reactions: oc-
casionally, transient proteinuria, and rarely, oliguria or anuria. Allergic reactions: asthmatic attacks,
nasal and conjunctival symptoms, dermal reactions such as urticaria with or without pruritus, as
well as pleomorphic rashes, sneezing and lacrimation and, rarely, anaphylactic reactions. Rare
fatalities have occurred, due to this or unknown causes. Signs and symptoms related to the
respiratory system: pulmonary or laryngeal edema, bronchospasm, dyspnea; or to the nervous
system: restlessness, tremors, convulsions. Other reactions: flushing, pain, warmth, metallic taste,
nausea, vomiting, anxiety, headache, confusion, pallor, weakness, sweating, localized areas of
edema, especially facial cramps, neutropenia, and dizziness. Rarely, immediate or delayed rigors can
occur, sometimes accompanied by hyperpyrexia. Infrequently, “iodism” (salivary gland swelling)
from organic iodinated compounds appears two days after exposure and subsides by the sixth day.
In general, the reactions which are known to occur upon parenteral administration of iodinated
contrast agents are possible with any nonionic agent. Approximately 95 percent of adverse
reactions accompanying the use of water-soluble intravascularly administered contrast agents are
mild to moderate in degree. However, severe, life-threatening anaphylactoid reactions, mostly of
cardiovascular origin, have occurred. Reported incidences of death range from 6.6 per 1 million
(0.00066 percent) to 1 in 10,000 (0.01 percent). Most deaths occur during injection or 5 to 10 minutes
later; the main feature being cardiac arrest with cardiovascular disease as the main aggravating
factor. Isolated reports of hypotensive collapse and shock are found in the literature. The incidence
of shock is estimated to be 1 out of 20,000 (0.005 percent) patients.
Adverse reactions to injectable contrast media fall into two categories: chemotoxic reactions and
idiosyncratic reactions.
Chemotoxic reactions result from the physicochemical properties of the contrast media, the dose,
and speed of injection. All hemodynamic disturbances and injuries to organs or vessels perfused by
the contrast medium are included in this category.
Idiosyncratic reactions include all other reactions. They occur more frequently in patients 20 to 40
years old. Idiosyncratic reactions may or may not be dependent on the amount of dose injected, the
speed of injection, and the radiographic procedure. Idiosyncratic reactions are subdivided into
minor, intermediate, and severe. The minor reactions are self-limited and of short duration; the
severe reactions are life-threatening and treatment is urgent and mandatory.
The reported incidence of adverse reactions to contrast media in patients with a history of allergy
are twice that of the general population. Patients with a history of previous reactions to a contrast
medium are three times more susceptible than other patients. However, sensitivity to contrast
media does not appear to increase with repeated examinations.
Most adverse reactions to injectable contrast media appear within 1 to 3 minutes after the start of
injection, but delayed reactions may occur.
Regardless of the contrast agent employed, the overall estimated incidence of serious adverse
reactions is higher with angiocardiography than with other procedures. Cardiac decompensation,
serious arrhythmias, angina pectoris, or myocardial ischemia or infarction may occur during angio-
cardiography and left ventriculography. Electrocardiographic and hemodynamic abnormalities
occur less frequently with OMNIPAQUE than with diatrizoate meglumine and diatrizoate sodium
injection.
OVERDOSAGE
Overdosage may occur. The adverse effects of overdosage are life-threatening and affect mainly the
pulmonary and cardiovascular systems. The symptoms include: cyanosis, bradycardia, acidosis,
pulmonary hemorrhage, convulsions, coma, and cardiac arrest. Treatment of an overdosage is
directed toward the support of all vital functions, and prompt institution of symptomatic therapy.
The intravenous LD50 values of OMNIPAQUE (in grams of iodine per kilogram body weight) are 24.2 in
mice and 15.0 in rats.
DOSAGE AND ADMINISTRATION — General
As with all radiopaque contrast agents, the lowest dose of OMNIPAQUE necessary to obtain
adequate visualization should be used. A lower dose may reduce the possibility of an adverse
reaction. Most procedures do not require use of either the maximum volume or the highest
concentration of OMNIPAQUE. The combination of volume and concentration of OMNIPAQUE to be
used should be carefully individualized accounting for factors such as age, body weight, size of the
vessel and the rate of blood flow within the vessel. Other factors such as anticipated pathology,
degree and extent of opacification required, structure(s) or area to be examined, disease processes
affecting the patient, and equipment and technique to be employed should be considered.
Sterile technique must be used in all vascular injections involving contrast media.
Withdrawal of contrast agents from their containers should be accomplished under aseptic condi-
tions with sterile equipment. Sterile techniques must be used with any invasive procedure.
If nondisposable equipment is used, scrupulous care should be taken to prevent residual contami-
nation with traces of cleansing agents.
It may be desirable that solutions of radiopaque diagnostic agents be used at body temperature
when injected.
Parenteral products should be inspected visually for particulate matter and discoloration prior to
administration whenever solution and container permit. Solutions of OMNIPAQUE should be used
only if clear and within the normal colorless to pale yellow range. If particulate matter or
discoloration is present, do not use.
INDIVIDUAL INDICATIONS AND USAGE
ANGIOCARDIOGRAPHY
Pharmacology—Hemodynamic Changes
OMNIPAQUE 350 at a concentration of 350 mgI/mL is indicated in adults for angiocardiography
(ventriculography, aortic root injections, and selective coronary arteriography).
OMNIPAQUE 350 at a concentration of 350 mgI/mL is indicated in children for angiocardiography
(ventriculography, pulmonary arteriography, and venography, and studies of the collateral arteries).
urography. Therefore, careful consideration of the potential risks should be given before performing
this radiographic procedure in these patients.
Immediately following surgery, excretory urography should be used with caution in renal transplant
recipients.
The possibility of a reaction, including serious, life-threatening, fatal, anaphylactoid or cardiovascu-
lar reactions, should always be considered (see ADVERSE REACTIONS: Intravascular—General). It is of
utmost importance that a course of action be carefully planned in advance for immediate treatment
of serious reactions, and that adequate and appropriate personnel be readily available in case of
any reaction.
The possibility of an idiosyncratic reaction in susceptible patients should always be considered (see
ADVERSE REACTIONS: Intravascular—General). The susceptible population includes, but is not limited
to, patients with a history of a previous reaction to contrast media, patients with a known sensitivity
to iodine per se, and patients with a known clinical hypersensitivity: bronchial asthma, hay fever, and
food allergies.
The occurrence of severe idiosyncratic reactions has prompted the use of several pretesting
methods. However, pretesting cannot be relied upon to predict severe reactions and may itself be
hazardous for the patient. It is suggested that a thorough medical history with emphasis on allergy
and hypersensitivity, prior to the injection of any contrast media, may be more accurate than
pretesting in predicting potential adverse reactions.
A positive history of allergies or hypersensitivity does not arbitrarily contraindicate the use of a
contrast agent where a diagnostic procedure is thought essential, but caution should be exercised
(see ADVERSE REACTIONS: Intravascular—General). Premedication with antihistamines or corticos-
teroids to avoid or minimize possible allergic reactions in such patients should be considered and
administered using separate syringes. Recent reports indicate that such pretreatment does not
prevent serious life-threatening reactions, but may reduce both their incidence and severity.
Even though the osmolality of OMNIPAQUE is low compared to diatrizoate- or iothalamate-based
ionic agents of comparable iodine concentration, the potential transitory increase in the circulatory
osmotic load in patients with congestive heart failure requires caution during injection. These
patients should be observed for several hours following the procedure to detect delayed
hemodynamic disturbances.
General anesthesia may be indicated in the performance of some procedures in selected adult
patients; however, a higher incidence of adverse reactions has been reported in these patients, and
may be attributable to the inability of the patient to identify untoward symptoms, or to the
hypotensive effect of anesthesia which can reduce cardiac output and increase the duration of
exposure to the contrast agent.
Angiography should be avoided whenever possible in patients with homocystinuria, because of the
risk of inducing thrombosis and embolism.
In angiographic procedures, the possibility of dislodging plaques or damaging or perforating the
vessel wall should be borne in mind during the catheter manipulations and contrast medium
injection. Test injections to ensure proper catheter placement are recommended.
Selective coronary arteriography should be performed only in those patients in whom the expected
benefits outweigh the potential risk. The inherent risks of angiocardiography in patients with chronic
pulmonary emphysema must be weighed against the necessity for performing this procedure.
When OMNIPAQUE is to be injected using plastic disposable syringes, the contrast medium should
be drawn into the syringe and used immediately.
If nondisposable equipment is used, scrupulous care should be taken to prevent residual contami-
nation with traces of cleansing agents.
Parenteral products should be inspected visually for particulate matter and discoloration prior
to administration. If particulate matter or discoloration is present, do not use.
Information for Patients
Patients receiving injectable radiopaque diagnostic agents should be instructed to:
1. Inform your physician if you are pregnant (see CLINICAL PHARMACOLOGY—Intravascular).
2. Inform your physician if you are diabetic or if you have multiple myeloma, pheochromocytoma,
homozygous sickle cell disease, or known thyroid disorder (see WARNINGS).
3. Inform your physician if you are allergic to any drugs, food, or if you had any reactions to previous
injections of dyes used for x-ray procedures (see PRECAUTIONS—General).
4. Inform your physician about any other medications you are currently taking, including non-
prescription drugs, before you are administered this drug.
Drug/Laboratory Test Interaction
If iodine-containing isotopes are to be administered for the diagnosis of thyroid disease, the iodine-
binding capacity of thyroid tissue may be reduced for up to 2 weeks after contrast medium 
administration. Thyroid function tests which do not depend on iodine estimation, eg, T3 resin uptake
or direct thyroxine assays, are not affected.
Many radiopaque contrast agents are incompatible in vitro with some antihistamines and many
other drugs; therefore, no other pharmaceuticals should be admixed with contrast agents.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No long-term animal studies have been performed to evaluate carcinogenic potential, mutagenesis,
or whether OMNIPAQUE can affect fertility in men or women.
Pregnancy Category B
Reproduction studies have been performed in rats and rabbits with up to 100 times the recom-
mended human dose. No evidence of impaired fertility or harm to the fetus has been demonstrated
due to OMNIPAQUE. There are, however, no studies in pregnant women. Because animal reproduc-
tion studies are not always predictive of human response, this drug should be used during
pregnancy only if clearly needed.
Nursing Mothers
It is not known to what extent iohexol is excreted in human milk. However, many injectable contrast
agents are excreted unchanged in human milk. Although it has not been established that serious
adverse reactions occur in nursing infants, caution should be exercised when intravascular contrast
media are administered to nursing women. Bottle feedings may be substituted for breast feedings
for 24 hours following administration of OMNIPAQUE.
Pediatric Use
Pediatric patients at higher risk of experiencing adverse events during contrast medium administra-
tion may include those having asthma, a sensitivity to medication and/or allergens, congestive heart
failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age.
ADVERSE REACTIONS: Intravascular—General
Adverse reactions following the use of OMNIPAQUE 140, OMNIPAQUE 240, OMNIPAQUE 300, and
OMNIPAQUE 350 are usually of mild to moderate severity. However, serious, life-threatening and
fatal reactions, mostly of cardiovascular origin, have been associated with the administration of
iodine-containing contrast media, including OMNIPAQUE. The injection of contrast media is 
frequently associated with the sensation of warmth and pain, especially in peripheral angiography;
pain and warmth are less frequent and less severe with OMNIPAQUE than with many contrast media.
Cardiovascular System: Arrhythmias including PVCs and PACs (2%), angina/chest pain (1%), and
hypotension (0.7%). Others including cardiac failure, asystole, bradycardia, tachycardia, and
vasovagal reaction were reported with an individual incidence of 0.3% or less. In controlled clinical
trials involving 1485 patients, one fatality occurred. A cause and effect relationship between this
death and iohexol has not been established.
Nervous System: Vertigo (including dizziness and lightheadedness) (0.5%), pain (3%), vision abnor-
malities (including blurred vision and photomas) (2%), headache (2%), and taste perversion (1%).
Others including anxiety, fever, motor and speech dysfunction, convulsion, paresthesia, somnolence,
stiff neck, hemiparesis, syncope, shivering, transient ischemic attack, cerebral infarction, and
nystagmus were reported, with an individual incidence of 0.3% or less.
4
OMNIPAQUE (iohexol) Injection 


OMNIPAQUE 300 at a concentration of 300 mgI/mL is indicated in children for angiocardiography
(ventriculography).
After both ventricular and coronary injection, decreases in systolic pressure were less pronounced
and returned to baseline values earlier with OMNIPAQUE 350 than with diatrizoate meglumine and
diatrizoate sodium injection.
OMNIPAQUE 350 produced less Q-T interval prolongation than seen with diatrizoate meglumine and
diatrizoate sodium injection.
In children, after injection of all sites, but particularly following ventricular and pulmonary artery
injections, decreases in both systolic and diastolic intravascular pressure were significantly less pro-
nounced with OMNIPAQUE 350 than with diatrizoate meglumine and diatrizoate sodium injection. In
children, OMNIPAQUE 350 produced significantly less shortening of the R-R interval than seen with
diatrizoate meglumine and diatrizoate sodium injection.
If repeat injections are made in rapid succession, all these changes are likely to be more pronounced.
(See DOSAGE AND ADMINISTRATION.)
Precautions
During administration of large doses of OMNIPAQUE 350, continuous monitoring of vital signs is
desirable. Caution is advised in the administration of large volumes to patients with incipient heart
failure because of the possibility of aggravating the preexisting condition. Hypotension should be
corrected promptly since it may induce serious arrhythmias.
Special care regarding dosage should be observed in patients with right ventricular failure,
pulmonary hypertension, or stenotic pulmonary vascular beds because of the hemodynamic
changes which may occur after injection into the right heart outflow tract. (See PRECAUTIONS—
General.)
Pediatric patients at higher risk of experiencing adverse events during contrast medium administra-
tion may include those having asthma, a sensitivity to medication and/or allergens, congestive heart
failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age.
Adverse Reactions
Cardiovascular system reactions in angiocardiography included angina (8%), hypotension (2.5%),
bradycardia (1.0%), and tachycardia (1.0%). (See ADVERSE REACTIONS: Intravascular—General.)
Dosage and Administration
The individual dose or volume is determined by the size of the structure to be visualized, the
anticipated degree of hemodilution, and valvular competence. Weight is a minor consideration in
adults, but must be considered in infants and young children. The volume of each individual injection
is a more important consideration than the total dosage used. When large individual volumes are
administered, as in ventriculography and aortography, it has been suggested that several minutes
be permitted to elapse between each injection to allow for subsidence of possible hemodynamic
disturbances.
The recommended single injection volume of OMNIPAQUE 350 for angiocardiographic procedures in
adults and the recommended single injection volumes of OMNIPAQUE 350 and OMNIPAQUE 300 for
angiographic procedures in children are as follows:
Ventriculography
Adults: The usual adult volume for a single injection is 40 mL with a range of 30 mL to 60 mL. This
may be repeated as necessary. When combined with selective coronary arteriography, the total
administered volume should not exceed 250 mL (87.5 gI).
Pediatrics: The usual single injection dose of OMNIPAQUE 350 is 1.25 mL/kg of body weight with a
range of 1.0 mL/kg to 1.5 mL/kg. For OMNIPAQUE 300 the usual single injection dose is 1.75 mL/kg
with a range of 1.5 mL/kg to 2.0 mL/kg. When multiple injections are given, the total administered
dose should not exceed 5 mL/kg up to a total volume of 250 mL of OMNIPAQUE 350 or up to a total
volume of 291 mL of OMNIPAQUE 300.
Selective Coronary Arteriography
The usual adult volume for right or left coronary arteriography is 5 mL (range 3 mL to 14 mL) per
injection.
Aortic Root and Arch Study When Used Alone
The usual adult single injection volume is 50 mL, with a range of 20 mL to 75 mL.
Pulmonary Angiography
Pediatrics: The usual single injection dose is 1.0 mL/kg of OMNIPAQUE 350.
Combined Angiocardiographic Procedures
Multiple Procedures
Adults: The visualization of multiple vascular systems and target organs is possible during a single
radiographic examination of the patient.
Large doses of OMNIPAQUE 350 were well tolerated in angiographic procedures requiring multiple
injections.
The maximum total volume for multiple procedures should not exceed 250 mL of 350 mgI/mL (87.5
gI).
Pediatrics: Visualization of multiple vascular systems and target organs is possible during a single
radiographic examination of the patient.
The maximum total dose for multiple injection procedures should not exceed 5.0 mL/kg up to a total
volume of 250 mL of OMNIPAQUE 350 or 6.0 mL/kg up to a total volume of 291 mL of OMNIPAQUE
300.
AORTOGRAPHY AND SELECTIVE VISCERAL ARTERIOGRAPHY
OMNIPAQUE 300 at a concentration of 300 mgI/mL and OMNIPAQUE 350 at a concentration of 350
mgI/mL are indicated in adults for use in aortography and selective visceral arteriography including
studies of the aortic arch, ascending aorta, and abdominal aorta and its branches (celiac,
mesenteric, renal, hepatic and splenic arteries).
OMNIPAQUE 350 at a concentration of 350 mgI/mL is indicated in children for use in aortography
including studies of the aortic root, aortic arch, ascending and descending aorta.
Precautions
Under conditions of slowed aortic circulation there is an increased likelihood for aortography to
cause muscle spasm. Occasional serious neurologic complications, including paraplegia, have also
been reported in patients with aortoiliac obstruction, femoral artery obstruction, abdominal com-
pression, hypotension, hypertension, spinal anesthesia, and injection of vasopressors to increase
contrast. In these patients the concentration, volume and number of repeat injections of the
medium should be maintained at a minimum with appropriate intervals between injections. The
position of the patient and catheter tip should be carefully monitored.
Entry of a large aortic dose into the renal artery may cause, even in the absence of symptoms,
albuminuria, hematuria, and an elevated creatinine and urea nitrogen. Rapid and complete return
of function usually follows. (See PRECAUTIONS—General.)
Adverse Reactions
See ADVERSE REACTIONS: Intravascular—General, and ADVERSE REACTIONS—ANGIOCARDIOGRAPHY.
Dosage and Administration
Adults: The usual adult volume as a single injection is 50 mL to 80 mL for the aorta, 30 mL to 60 mL
for major branches including celiac and mesenteric arteries, and 5 mL to 15 mL for renal arteries.
Repeated injections may be performed if indicated, but the total volume should not exceed 291 mL
of OMNIPAQUE 300 or 250 mL of OMNIPAQUE 350 (87.5 gI).
Pediatrics: The usual single injection dose is 1.0 mL/kg of OMNIPAQUE 350 and should not exceed 5.0
mL/kg up to a total volume of 250 mL of OMNIPAQUE 350.
CEREBRAL ARTERIOGRAPHY
OMNIPAQUE 300 at a concentration of 300 mgI/mL is indicated in adults for use in cerebral
arteriography.
The degree of pain and flushing as the result of the use of OMNIPAQUE 300 in cerebral arteriography
is less than that seen with comparable injections of many contrast media.
In cerebral arteriography, patients should be appropriately prepared consistent with existing or
suspected disease states.
Precautions
Cerebral arteriography should be undertaken with extreme care with special caution in elderly
patients, patients in poor clinical condition, advanced arteriosclerosis, severe arterial hypertension,
recent cerebral embolism or thrombosis, and cardiac decompensation.
Since the contrast medium is given by rapid injection, the patient should be monitored for possible
untoward reactions. (See PRECAUTIONS—General.)
Adverse Reactions
Cerebral arteriography with water-soluble contrast media has been associated with temporary
neurologic complications including seizures, drowsiness, transient paresis, and mild disturbances in
vision such as photomas of 1-second or less duration.
Central nervous system reactions in cerebral arteriography included photomas (15%), headache
(5.5%), and pain (4.5%). (See ADVERSE REACTIONS: Intravascular—General.)
Dosage and Administration
OMNIPAQUE 300 is recommended for cerebral arteriography at the following volumes: common
carotid artery (6 mL to 12 mL), internal carotid artery (8 mL to 10 mL), external carotid artery (6 mL
to 9 mL), and vertebral artery (6 mL to 10 mL).
CONTRAST ENHANCED COMPUTED TOMOGRAPHY
OMNIPAQUE 240 at a concentration of 240 mgI/mL, OMNIPAQUE 300 at a concentration of 300
mgI/mL, and OMNIPAQUE 350 at a concentration of 350 mgI/mL are indicated in adults for use in
intravenous contrast enhanced computed tomographic head and body imaging by rapid injection or
infusion technique.
OMNIPAQUE 240 at a concentration of 240 mgI/mL and OMNIPAQUE 300 at a concentration of 300
mgI/mL are indicated in children for use in intravenous contrast enhanced computed tomographic
head imaging by rapid bolus injection.
CT SCANNING OF THE HEAD
OMNIPAQUE may be used to redefine diagnostic precision in areas of the brain which may not
otherwise have been satisfactorily visualized.
Tumors
OMNIPAQUE may be useful to investigate the presence and extent of certain malignancies such as:
gliomas including malignant gliomas, glioblastomas, astrocytomas, oligodendrogliomas and gan-
gliomas, ependymomas, medulloblastomas, meningiomas, neuromas, pinealomas, pituitary adeno-
mas, carniopharyngiomas, germinomas, and metastatic lesions. The usefulness of contrast en-
hancement for the investigation of the retrobulbar space and in cases of low grade or infiltrative
glioma has not been demonstrated. In calcified lesions, there is less likelihood of enhancement.
Following therapy, tumors may show decreased or no enhancement. The opacification of the inferior
vermis following contrast media administration has resulted in false-positive diagnosis in a number
of otherwise normal studies.
Nonneoplastic Conditions
OMNIPAQUE may be beneficial in the image enhancement of nonneoplastic lesions. Cerebral
infarctions of recent onset may be better visualized with contrast enhancement, while some
infarctions are obscured if contrast medium is used. The use of iodinated contrast media results in
enhancement in about 60 percent of cerebral infarctions studied from one to four weeks from the
onset of symptoms.
Sites of active infection may also be enhanced following contrast medium administration.
Arteriovenous malformations and aneurysms will show contrast enhancement. For these vascular
lesions the enhancement is probably dependent on the iodine content of the circulating blood pool.
Hematomas and intraparenchymal bleeders seldom demonstrate contrast enhancement. However,
in cases of intraparenchymal clot, for which there is no obvious clinical explanation, contrast media
administration may be helpful in ruling out the possibility of associated arteriovenous malformation.
CT SCANNING OF THE BODY
OMNIPAQUE may be useful for enhancement of computed tomographic images for detection and
evaluation of lesions in the liver, pancreas, kidneys, aorta, mediastinum, pelvis, abdominal cavity,
and retroperitoneal space.
Enhancement of computed tomography with OMNIPAQUE may be of benefit in establishing
diagnoses of certain lesions in these sites with greater assurance than is possible with CT alone. In
other cases, the contrast agent may allow visualization of lesions not seen with CT alone (ie, tumor
extension) or may help to define suspicious lesions seen with unenhanced CT (ie, pancreatic cyst).
For information regarding the use of dilute oral plus intravenous OMNIPAQUE in CT of the abdomen,
see INDIVIDUAL INDICATIONS AND USAGE—Oral Use.
Precautions
See PRECAUTIONS—General.
Adverse Reactions
Immediately following intravascular injection of contrast medium, a transient sensation of mild
warmth is not unusual. Warmth is less frequent with OMNIPAQUE than with ionic media. (See
ADVERSE REACTIONS: Intravascular—General.)
Dosage and Administration
The concentration and volume required will depend on the equipment and imaging technique used.
OMNIPAQUE (iohexol) Injection
The dosage recommended for use in adults for contrast enhanced computed tomography is as
follows:
Head Imaging
70 mL to 150 mL (21 gI to 45 gI) of OMNIPAQUE 300 (300 mgI/mL)
by Injection:
80 mL (28 gI) of OMNIPAQUE 350 (350 mgI/mL)
Head Imaging
120 mL to 250 mL (29 gI to 60 gI) of OMNIPAQUE 240 (240 mgI/mL)
by Infusion:
Body Imaging
50 mL to 200 mL (15 gI to 60 gI) of OMNIPAQUE 300 (300 mgI/mL)
by Injection:
60 mL to 100 mL (21 gI to 35 gI) of OMNIPAQUE 350 (350 mgI/mL)
The dosage recommended for use in children for contrast enhanced computed tomographic head
imaging is 1.0 mL/kg to 2.0 mL/kg for OMNIPAQUE 240 or OMNIPAQUE 300. It should not be
necessary to exceed a maximum dose of 28 gI with OMNIPAQUE 240 or 35 gI with OMNIPAQUE 300.
DIGITAL SUBTRACTION ANGIOGRAPHY
Intravenous Administration
OMNIPAQUE 350 at a concentration of 350 mgI/mL is indicated in adults for use in intravenous
digital subtraction angiography (I.V.DSA) of the vessels of the head, neck, and abdominal, renal and
peripheral vessels.
Arteriograms of diagnostic quality can be obtained following the intravenous administration of
contrast media employing digital subtraction and computer imaging enhancement techniques. The
intravenous route of administration using these techniques has the advantage of being less invasive
than the corresponding selective catheter placement of medium. The dose is administered into a
5
OMNIPAQUE (iohexol) Injection 


peripheral vein, the superior vena cava or right atrium, usually by mechanical injection although
sometimes by rapid manual injection. The technique has been used to visualize the ventricles, aorta
and most of its larger branches, including the carotids, cerebrals, vertebrals, renal, celiac, mesenter-
ics, and the major peripheral vessels of the limbs. Radiographic visualization of these structures is
possible until significant hemodilution occurs.
OMNIPAQUE 350 can be injected intravenously as a rapid bolus to provide arterial visualization using
digital subtraction radiography. Preprocedural medications are not considered necessary.
OMNIPAQUE 350 has provided diagnostic arterial radiographs in about 95% of patients. In some
cases, poor arterial visualization has been attributed to patient movement. OMNIPAQUE 350 is very
well tolerated in the vascular system. Patient discomfort (general sensation of heat and/or pain)
following injection is less than with various other contrast media.
Precautions
Since the contrast medium is usually administered mechanically under high pressure, rupture of
smaller peripheral veins can occur. It has been suggested that this can be avoided by using an
intravenous catheter threaded proximally beyond larger tributaries or, in the case of the antecubital
vein, into the superior vena cava. Sometimes the femoral vein is used. (See PRECAUTIONS—General.)
Adverse Reactions
Cardiovascular system reactions in digital arteriography included transient PVCs (16%) and PACs
(6.5%). (See ADVERSE REACTIONS: Intravascular—General.)
Dosage and Administration
The usual injection volume of OMNIPAQUE 350 for the intravenous digital technique is 30 mL to 50
mL of a 350 mgI/mL solution. This is administered as a bolus at 7.5 to 30 mL/second using a pressure
injector. The volume and rate of injection will depend primarily on the type of equipment and
technique used.
Frequently three or more injections may be required, up to a total volume not to exceed 250 mL (87.5
gI).
Intra-arterial Administration
OMNIPAQUE 140 at a concentration of 140 mgI/mL is indicated for use in intra-arterial digital
subtraction angiography of head, neck, abdominal, renal and peripheral vessels. The intra-arterial
route of administration has the advantages of allowing a lower total dose of contrast agent since
there is less hemodilution than with the intravenous route of administration. Patients with poor
cardiac output would be expected to have better contrast enhancement following intra-arterial
administration as compared with intravenous administration. A higher concentration of contrast
agent may be needed to facilitate catheter placement under fluoroscopic control.
Precautions
High pressure intra-arterial injections may cause the rupture of smaller peripheral arteries. (See
PRECAUTIONS—General.)
Adverse Reactions
Central nervous system reactions in intra-arterial digital angiography include transient ischemia
attacks (1.6%) and cerebral infarctions (1.6%). These occurred in high risk patients having a cerebral
examination and the relationship to the contrast medium was uncertain. (See ADVERSE REAC-
TIONS—General.) Headache occurred in 6.3% of the patients, all of whom were having cerebral ex-
aminations.
Dosage and Administration
Mechanical or hand injection can be used to administer one or more bolus intra-arterial injections
of OMNIPAQUE 140. The volume and rate of injection will depend on the type of equipment,
technique used, and the vascular area to be visualized. The following volumes and rates of injection
have been used with OMNIPAQUE 140.
Volume/Injection
Rate of Injection
Arteries
(mL)
(mL/sec)
Aorta
20-45
8-20
Carotid
5-10
3-6
Femoral
9-20
3-6
Vertebral
4-10
2-8
Renal
6-12
3-6
Other Branches of the Aorta
8-25
3-10
(includes subclavian, axillary,
innominate and iliac)
PERIPHERAL ANGIOGRAPHY
OMNIPAQUE 300 at a concentration of 300 mgI/mL or OMNIPAQUE 350 at a concentration of 350
mgI/mL is indicated in adults for use in peripheral arteriography. OMNIPAQUE 240 at a
concentration of 240 mgI/mL or OMNIPAQUE 300 at a concentration of 300 mgI/mL is indicated in
adults for use in peripheral venography.
Sedative medication may be employed prior to use. Anesthesia is not considered necessary.
Patient discomfort during and immediately following injection is substantially less than that
following injection of various other contrast media. Moderate to severe discomfort is very unusual.
Precautions
Pulsation should be present in the artery to be injected. In thromboangiitis obliterans, or ascending
infection associated with severe ischemia, angiography should be performed with extreme caution,
if at all. (See PRECAUTIONS—General.)
Adverse Reactions
A transient sensation of mild warmth is usual, immediately following injection. This has not
interfered with the procedure.
In phlebography the incidence of leg pain was 21%. This usually was mild and lasted a short time
after injection. (See ADVERSE REACTIONS: Intravascular—General.)
Dosage and Administration
The volume required will depend on the size, flow rate, and disease state of the injected vessel and
on the size and condition of the patient, as well as the imaging technique used.
The dosage recommended for use in peripheral angiography is as follows:
Aortofemoral runoffs:
20 mL to 70 mL of OMNIPAQUE 350 (350 mgI/mL)
30 mL to 90 mL of OMNIPAQUE 300 (300 mgI/mL)
Selective arteriograms:
10 mL to 30 mL of OMNIPAQUE 350 (350 mgI/mL)
(femoral/iliac)
10 mL to 60 mL of OMNIPAQUE 300 (300 mgI/mL)
Venography (per leg):
20 mL to 150 mL of OMNIPAQUE 240 (240 mgI/mL)
40 mL to 100 mL of OMNIPAQUE 300 (300 mgI/mL)
EXCRETORY UROGRAPHY
OMNIPAQUE 300 at a concentration of 300 mgI/mL or OMNIPAQUE 350 at a concentration of 350
mgI/mL is indicated for use in adults in excretory urography to provide diagnostic contrast of the
urinary tract.
OMNIPAQUE 300 at a concentration of 300 mgI/mL is indicated in children for excretory urography.
(See Section III for information on voiding cystourethrography.)
For pharmacokinetics of excretion in adults, see CLINICAL PHARMACOLOGY—Intravascular.
Precautions
Preparatory dehydration is not recommended in the elderly, infants, young children, diabetic or
azotemic patients, or in patients with suspected myelomatosis.
Pediatric patients at higher risk of experiencing adverse events during contrast medium administra-
tion may include those having asthma, a sensitivity to medication and/or allergens, congestive heart
failure, a serum creatinine greater than 1.5 mg/dL or those less than 12 months of age.
Since there is a possibility of temporary suppression of urine formation, it is recommended that a
suitable interval elapse before excretory urography is repeated, especially in patients with
unilateral or bilateral reduction in renal function. (See PRECAUTIONS—General.)
Adverse Reactions
See ADVERSE REACTIONS: Intravascular—General.
Dosage and Administration
Adults: OMNIPAQUE 300 and OMNIPAQUE 350 at dosages from 200 mgI/kg body weight to 350
mgI/kg body weight have produced diagnostic opacification of the excretory system in patients with
normal renal function.
Pediatrics
Excretory Urography
OMNIPAQUE 300 at doses of 0.5 mL/kg to 3.0 mL/kg of body weight has produced diagnostic
opacification of the excretory tract. The usual dose for children is 1.0 mL/kg to 1.5 mL/kg. Dosage for
infants and children should be administered in proportion to age and body weight. The total
administered dose should not exceed 3 mL/kg.
SECTION III
CLINICAL PHARMACOLOGY—OraI/Body Cavity Use
For most body cavities, the injected iohexol is absorbed into the surrounding tissue and eliminated by
the kidneys and bowel as previously described in SECTION II, CLINICAL PHARMACOLOGY—Intravascu-
lar. Examinations of the uterus (hysterosalpingography) and bladder (voiding cystourethrography)
involve the almost immediate drainage of contrast medium from the cavity upon conclusion of the
radiographic procedure.
Orally administered iohexol is very poorly absorbed from the normal gastrointestinal tract. Only 0.1
to 0.5 percent of the oral dose was excreted by the kidneys. This amount may increase in the
presence of bowel perforation or bowel obstruction. Iohexol is well tolerated and readily absorbed if
leakage into the peritoneal cavity occurs.
Visualization of the joint spaces, uterus, fallopian tubes, peritoneal herniations, pancreatic and bile
ducts, and bladder can be accomplished by direct injection of contrast medium into the region to be
studied. The use of appropriate iodine concentrations assures diagnostic density.
Orally administered OMNIPAQUE produces good visualization of the gastrointestinal tract.
OMNIPAQUE is particularly useful when barium sulfate is contraindicated as in patients with
suspected bowel perforation or those where aspiration of contrast medium is a possibility.
INDICATIONS AND USAGE, GENERAL—Oral/Body Cavity Use
OMNIPAQUE 240, OMNIPAQUE 300, and OMNIPAQUE 350 have osmolalities from approximately 1.8
to 3.0 times that of plasma (285 mOsm/kg water) and are hypertonic under conditions of use.
Adults: OMNIPAQUE 350 is indicated in adults for arthrography and oral pass-thru examination of
the gastrointestinal tract.
OMNIPAQUE 300 is indicated in adults for arthrography and hysterosalpingography.
OMNIPAQUE 240 is indicated in adults for arthrography, endoscopic retrograde pancreatography
and cholangiopancreatography, herniography, and hysterosalpingography.
OMNIPAQUE diluted to concentrations from 6 mgI/mL to 9 mgI/mL administered orally in conjunction
with OMNIPAQUE 300 at a concentration of 300 mgI/mL administered intravenously is indicated in
adults for contrast enhanced computed tomography of the abdomen.
Children: OMNIPAQUE 300 is indicated in children for examination of the gastrointestinal tract.
OMNIPAQUE 240 is indicated in children for examination of the gastrointestinal tract.
OMNIPAQUE 180 is indicated in children for examination of the gastrointestinal tract.
OMNIPAQUE diluted to concentrations from 50 mgI/mL to 100 mgI/mL is indicated in children for
voiding cystourethrography.
OMNIPAQUE diluted to concentrations from 9 mgI/mL to 21 mgI/mL administered orally in conjunc-
tion with OMNIPAQUE 240 at a concentration of 240 mgI/mL or OMNIPAQUE 300 at a concentration
of 300 mgI/mL administered intravenously is indicated in children for use in contrast enhanced
computed tomography of the abdomen.
CONTRAINDICATIONS
OMNIPAQUE should not be administered to patients with a known hypersensitivity to iohexol.
WARNINGS—General
See SECTION II, WARNINGS—General.
PRECAUTIONS—General
See SECTION II, PRECAUTIONS—General.
Orally administered hypertonic contrast media draw fluid into the intestines which, if severe enough,
could result in hypovolemia. Likewise, in infants and young children, the occurrence of diarrhea may
result in hypovolemia. Plasma fluid loss may be sufficient to cause a shock-like state which, if
untreated, could be dangerous. This is especially pertinent to the elderly, cachectic patients of any
age as well as infants and small children.
ADVERSE REACTIONS: Oral/Body Cavity Use—General
Body Cavities
In controlled clinical trials involving 285 adult patients for various body cavity examinations using
OMNIPAQUE 240, 300, and 350, the following adverse reactions were reported.
Cardiovascular System
Incidence > 1%: None
Incidence ≤1%: Hypertension
Nervous System
Incidence > 1%: Pain (26%)
Incidence ≤1%: Headache, somnolence, fever, muscle weakness, burning, unwell feeling, tremors,
lightheadedness, syncope
Respiratory System
None
Gastrointestinal System
Incidence > 1%: None
Incidence ≤1%: Flatulence, diarrhea, nausea, vomiting, abdominal pressure
Skin and Appendages
Incidence > 1%: Swelling (22%), heat (7%)
Incidence ≤1%: Hematoma at injection site
The most frequent reactions, pain and swelling, were almost exclusively reported after arthrography
and were generally related to the procedure rather than the contrast medium. Gastrointestinal
reactions were almost exclusively reported after oral pass-thru examinations. For additional infor-
mation on adverse reactions that may be expected with specific procedures, see INDIVIDUAL INDI-
CATIONS AND USAGE. For information on general adverse reactions to contrast media, see SECTION
II, ADVERSE REACTIONS: Intravascular—General.
No adverse reactions associated with the use of OMNIPAQUE for VCU procedures were reported in
51 pediatric patients studied.
Oral Use
See INDIVIDUAL INDICATIONS AND USAGE: Oral Use—Adverse Reactions.
6
OMNIPAQUE (iohexol) Injection 


To Achieve
Add
To
One Liter of
Stock Concentration
Volume
Water, Carbonated
Contrast Medium at
of OMNIPAQUE
(mL)
Beverage, Milk, or
A Final Concentration
(mgI/mL)
Juice
(mgI/mL) of
(mL)
6
240
25
975
300
20
980
350
17
983
9
240
38
962
300
30
970
350
26
974
12
240
50
950
300
40
960
350
35
965
15
240
63
937
300
50
950
350
43
957
18
240
75
925
300
60
940
350
52
948
21
240
88
912
300
70
930
350
60
940
Dilutions of OMNIPAQUE should be prepared just prior to use and any unused portion discarded after
the procedure.
VOIDING CYSTOURETHROGRAPHY (VCU)
OMNIPAQUE diluted to concentrations from 50 mgI/mL to 100 mgI/mL is indicated in children for
voiding cystourethrography. VCUs are often performed in conjunction with excretory urography.
Precautions
See PRECAUTIONS—General.
Since the VCU procedure requires instrumentation, special precautions should be observed in those
patients known to have an acute urinary tract infection. Filling of the bladder should be done at a
steady rate, exercising caution to avoid excessive pressure. Sterile procedures are essential.
Adverse Reactions
See ADVERSE REACTIONS—General.
Dosage and Administration
OMNIPAQUE may be diluted, utilizing aseptic technique, with Sterile Water for Injection to a concen-
tration of 50 mgI/mL to 100 mgI/mL for voiding cystourethrography. The concentration may vary
depending upon the patient’s size and age and also with the technique and equipment used.
Sufficient volume of contrast medium should be administered to adequately fill the bladder. The
usual volume ranges from 50 mL to 300 mL of OMNIPAQUE at a concentration of 100 mgI/mL and
50 mL to 600 mL of OMNIPAQUE at a concentration of 50 mgI/mL.
OMNIPAQUE may be diluted with Sterile Water for Injection as indicated in the table below:
To Achieve
Add To
A Final
Each 100 mL of OMNIPAQUE
Concentration
Sterile Water for Injection, USP (mL)
(mgI/mL)
OMNIPAQUE 240
OMNIPAQUE 300
OMNIPAQUE 350
100
140
200
250
90
167
233
289
80
200
275
338
70
243
330
400
60
300
400
483
50
380
500
600
Dilutions of OMNIPAQUE should be prepared just prior to use and any unused portion discarded after
the procedure.
ARTHROGRAPHY
OMNIPAQUE 240 at a concentration of 240 mgI/mL or OMNIPAQUE 300 at a concentration of 300
mgI/mL or OMNIPAQUE 350 at a concentration of 350 mgI/mL is indicated in radiography of the
knee joint in adults, and OMNIPAQUE 240 at a concentration of 240 mgI/mL or OMNIPAQUE 300 at a
concentration of 300 mgI/mL is indicated in radiography of the shoulder joint in adults, and
OMNIPAQUE 300 at a concentration of 300 mgI/mL is indicated in radiography of the
temporomandibular joint in adults. Arthrography may be helpful in the diagnosis of posttraumatic
or degenerative joint diseases, synovial rupture, the visualization of communicating bursae or cysts,
and in meniscography.
Precautions
See PRECAUTIONS—General.
Strict aseptic technique is required to prevent infection. Fluoroscopic control should be used to
ensure proper needle placement, prevent extracapsular injection, and prevent dilution of contrast
medium. Undue pressure should not be exerted during injection.
Adverse Reactions
Injection of OMNIPAQUE into the joint is associated with transient discomfort, ie, pain, swelling.
However, delayed, severe or persistent discomfort may occur occasionally. Severe pain may often
result from undue use of pressure or the injection of large volumes. Joint swelling after injection is
less with OMNIPAQUE than with high osmolar ionic contrast medium. These types of reactions are
generally procedurally dependent and of greater frequency when double-contrast technique is
employed.
Nervous system: Swelling sensation (42%), pain (29%), heat sensation (13%), and muscle weakness
(0.7%).
Skin and appendages: Hematoma at injection site (0.7%).
Dosage and Administration
Arthrography is usually performed under local anesthesia. The amount of OMNIPAQUE injected is
dependent on the size of the joint to be examined and the technique employed. Lower volumes of
contrast medium are usually injected for knee and shoulder arthrography when double-contrast
examinations using 15 mL to 100 mL of air are performed.
The following concentrations and volumes are recommended for normal adult knee, shoulder, and
temporomandibular joints but should serve as guidelines since joints may require more or less
contrast medium for optimal visualization.
OVERDOSAGE
See also SECTION II, OVERDOSAGE.
The recommended dose of OMNIPAQUE 350 at a concentration of 350 mgI/mL for adult oral pass-
thru examination of the gastrointestinal tract is 50 mL to 100 mL. In a Phase I study, 150 mL of
OMNIPAQUE 350 was administered orally to 11 healthy male subjects. The incidence of diarrhea was
91% (10 of 11) and abdominal cramping was 27% (3 of 11). Despite all of these events being mild and
transient the occurrences were more than double that seen at the recommended doses. It is
apparent from this finding that larger volumes of hypertonic contrast media, like OMNIPAQUE,
increase the osmotic load in the bowel, which may result in greater fluid shifts.
DOSAGE AND ADMINISTRATION—General
See SECTION II, DOSAGE AND ADMINISTRATION—General.
INDIVIDUAL INDICATIONS AND USAGE
Oral Use
Adults: OMNIPAQUE 350 at a concentration of 350 mgI/mL is indicated in adults for use in oral pass-
thru examination of the gastrointestinal tract.
OMNIPAQUE diluted to concentrations from 6 mgI/mL to 9 mgI/mL administered orally in conjunc-
tion with OMNIPAQUE 300 at a concentration of 300 mgI/mL administered intravenously is indicated
in adults for use in contrast enhanced computed tomography of the abdomen. Dilute oral plus
intravenous OMNIPAQUE may be useful when unenhanced imaging does not provide sufficient
delineation between normal loops of the bowel and adjacent organs or areas of suspected
pathology.
Children: OMNIPAQUE 300 at a concentration of 300 mgI/mL administered orally or rectally is
indicated in children for use in examination of the gastrointestinal tract.
OMNIPAQUE 240 at a concentration of 240 mgI/mL administered orally or rectally is indicated in
children for use in examination of the gastrointestinal tract.
OMNIPAQUE 180 at a concentration of 180 mgI/mL administered orally or rectally is indicated in
children for use in examination of the gastrointestinal tract.
OMNIPAQUE diluted to concentrations from 9 mgI/mL to 21 mgI/mL administered orally in
conjunction with OMNIPAQUE 240 at a concentration of 240 mgI/mL or OMNIPAQUE 300 at a
concentration of 300 mgI/mL administered intravenously is indicated in children for use in contrast
enhanced computed tomography of the abdomen.
Precautions
See PRECAUTIONS—General.
Adverse Reactions
Oral administration of OMNIPAQUE is most often associated with mild, transient diarrhea especially
when high concentrations and large volumes are administered. Nausea, vomiting, and moderate
diarrhea have also been reported following orally administered OMNIPAQUE, but much less 
frequently. For CT examinations using dilute oral plus intravenous contrast medium, adverse events
are more likely to be associated with the intravenous injection than the hypotonic oral solution. It
should be noted that serious or anaphylactoid reactions that may occur with intravascular
iodinated media are possible following administration by other routes.
Adults: In controlled clinical trials involving 54 adult patients for oral pass-thru examination of the
gastrointestinal tract using OMNIPAQUE 350, the following adverse reactions were reported:
diarrhea (42%), nausea (15%), vomiting (11%), abdominal pain (7%), flatulence (2%), and headache
(2%).
In controlled clinical studies involving 44 adult patients for dilute oral plus intravenous CT examina-
tion of the gastrointestinal tract using OMNIPAQUE 300, adverse reactions were limited to a single
report of vomiting (2%).
Children: In controlled clinical studies involving 58 pediatric patients for examination of the
gastrointestinal tract at concentrations of 180 and 300 mgI/mL, the following adverse reactions
were reported: diarrhea (36%), vomiting (9%), nausea (5%), fever (5%), hypotension (2%), abdominal
pain (2%), and urticaria (2%). In clinical studies an increased frequency and severity of diarrhea was
noted with an increase in the administered concentration and dose of the radiocontrast agent.
In controlled clinical studies involving 69 pediatric patients for dilute oral plus intravenous CT exami-
nation of the gastrointestinal tract using OMNIPAQUE 240 and OMNIPAQUE 300, adverse reactions
were limited to a single report of vomiting (1.4%).
Dosage and Administration
Adults: The recommended dosage of undiluted OMNIPAQUE 350 at a concentration of 350 mgI/mL
for oral pass-thru examination of the gastrointestinal tract in adults is 50 mL to 100 mL depending
on the nature of the examination and the size of the patient.
The recommended oral dosage of OMNIPAQUE diluted to concentrations of 6 mgI/mL to 9 mgI/mL
for contrast enhanced computed tomography of the abdomen in adults is 500 mL to 1000 mL.
Smaller administered volumes are needed as the concentration of the final solution is increased (see
Table below). In conjunction with dilute oral administration, the recommended dosage of
OMNIPAQUE 300 administered intravenously is 100 mL to 150 mL. The oral dose is administered
about 20 to 40 minutes prior to the intravenous dose and image acquisition.
Children: The dosage of undiluted OMNIPAQUE 300 at a concentration of 300 mgI/mL, OMNIPAQUE
240 at a concentration of 240 mgI/mL or OMNIPAQUE 180 at a concentration of 180 mgI/mL for oral
pass-thru examination of the gastrointestinal tract in children is dependent on the nature of the
examination and the size of the patient.  Based on clinical experience, it is recommended that
OMNIPAQUE 180 be used in children less than 3 months of age. OMNIPAQUE 180, OMNIPAQUE 240
or OMNIPAQUE 300 may be used in children 3 months of age and older. The following dosage
guidelines are recommended:
Age
Volume of OMNIPAQUE
Less than 3 months
5 — 30 mL
Three months to 3 years
Up  to  60 mL
Four years to 10 years
Up  to 80 mL
Greater than 10 years
Up  to  100 mL
When given rectally, larger volumes may be used.
The recommended oral dosage of OMNIPAQUE diluted to concentrations of 9 mgI/mL to 21 mgI/mL
for contrast enhanced computed tomography of the abdomen in children is 180 mL to 750 mL.
Smaller administered volumes are needed as the concentration of the final solution is increased (see
Table below). The total oral dose in grams of iodine should generally not exceed 5 gI for children
under 3 years of age and 10 gI for children from 3 to 18 years of age. The oral dosage may be given
all at once or over a period of 30 to 45 minutes if there is difficulty in consuming the required volume.
In conjunction with dilute oral administration the recommended dosage of OMNIPAQUE 240 and
OMNIPAQUE 300 is 2.0 mL/kg when administered intravenously with a range of 1.0 mL/kg to 2.0
mL/kg. Dosage for infants and children should be administered in proportion to age and body
weight. The total intravenously administered dose should not exceed 3 mL/kg. The oral dose is
administered about 30 to 60 minutes prior to the intravenous dose and image acquisition.
OMNIPAQUE may be diluted with water or beverage as follows:
7
OMNIPAQUE (iohexol) Injection 
Lower volumes
recommended
for double-contrast
examinations;
higher volumes
recommended
for single-contrast
examinations.}
KNEE
OMNIPAQUE 240    5 mL to 15 mL
OMNIPAQUE 300    5 mL to 15 mL
OMNIPAQUE 350    5 mL to 10 mL
SHOULDER
OMNIPAQUE 300    10 mL
OMNIPAQUE 240       3 mL
TEMPOROMANDIBULAR
OMNIPAQUE 300   0.5 mL to 1.0 mL




MediBeacon Inc. 
MB-102/ORFM Device 
Protocol No.  ORFM Pilot 2 
 Version 13.0 
 
 
18 June 2021 
CONFIDENTIAL INFORMATION  
Page 103 of 103 
 
 
Investigator Signature Page 
 
Protocol 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 
Protocol Number: 
ORFM Pilot 2 
Confidentiality and cGCP Compliance Statement 
I, the undersigned, have reviewed this protocol, including appendices and other documents that 
may be considered part of the investigational plan, and I will conduct the study as described in 
compliance with this protocol, GCP, the ethical principles defined by the World Medical 
Association Declaration of Helsinki (2008) and relevant ICH guidelines. 
Once the protocol has been approved by the IEC, I will not modify this protocol without 
obtaining prior approval of the MediBeacon Inc. and of the IEC.  I will submit the protocol 
modifications and/or any ICF modifications to MediBeacon Inc. and IEC, and approval will be 
obtained before any modifications are implemented. 
I understand that all information obtained during the conduct of the study with regard to the 
subjects’ state of health will be regarded as confidential.  No subjects’ names will be disclosed.  
All subjects will be identified by assigned numbers on all eCRFs, laboratory samples or source 
documents forwarded to the sponsor.  Clinical information may be reviewed by the sponsor or its 
agents or regulatory agencies.  Agreement must be obtained from the subject before disclosure of 
subject information to a third party. 
I will oversee all aspects of study conduct and will only appropriately delegate responsibilities to 
adequately qualified and trained staff. I will oversee the completion of source data collection 
such that all data collected for the study may be substantiated against accurate source medical 
records.  
Information developed in this clinical study may be disclosed by MediBeacon Inc. to other 
clinical investigators, regulatory agencies, or other health authority or government agencies as 
required. 
 
Investigator Signature 
Date