Back to resultsPharmacokinetics of MP-3180 and Use of Noninvasive Fluorescence Detection Device in Healthy Volunteers (ORFM-1B)
Primary Purpose
Glomerular Filtration Rate, Acute Kidney Injury
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Below target dose MP-3180
At target dose MP-3180
2 times above target dose MP-3180
4 times above target dose MP-3180
ORFM prototype
Iohexol comparator
Sponsored by
About this trial
This is an interventional basic science trial for Glomerular Filtration Rate focused on measuring Glomerular Filtration Rate, Acute Kidney Injury
Eligibility Criteria
Inclusion Criteria:
- Age: 22 years of age or older
- Sex: Males and not of childbearing potential females
- Capable of informed consent
Weight restrictions:
- at least 50 kg (110 lbs) for men
- at least 48 kg (106 lbs) for women
- all participants will have a Body Mass Index (BMI) less than or equal to 33 but greater than or equal to 19
- All participants should be judged by the Principal Investigator or Medical Sub-Investigator physician as normal and healthy during a pre-study medical evaluation performed within 28 days of the initial dose of study medication
Exclusion Criteria:
- Institutionalized participants will not be used
- History of any significant cardiovascular disease, renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic (including any history of seizure disorder), psychological, musculoskeletal disease or malignancies unless deemed not clinically significant by the Principal Investigator or Medical Sub-Investigator.
- Donation or loss of blood or plasma: 50 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.
- Intolerance to venipuncture.
- Participants who have received an investigational drug within 30 days prior to the initial dose of study medication.
- History of drug and/or alcohol abuse within the past year, unless currently enrolled in an abstinence program.
- History of allergy or hypersensitivity to MP-3180 or iohexol, or other related 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 or Medical Sub-Investigator, could contraindicate the participant's participation in this study.
- History of allergy or hypersensitivity to iodine containing contrast media or drugs.
- Acute illness at the time of either the pre-study medical evaluation or dosing.
Social Habits:
- Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication.
- Ingestion of any vitamins or herbal supplement within 7 days prior to the initial dose of study medication.
- Any significant change in dietary or exercise habits within the 48 hours prior to the initial dose of study medication.
Medications:
a. Use of any prescription or over-the-counter (OTC) medications within the 7 days prior to the initial dose of study medication.
- Not within normal limits or clinically significant for lab testing; serum chemistries, hematology, urinalysis.
Sites / Locations
- University of Maryland
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Below target dose MP-3180
2 times above target dose MP-3180
4 times above target dose MP-3180
At target dose MP-3180
Arm Description
0.5 µmol/kg (0.186 mg/kg) dose of MP-3180 by IV one time over 2 minutes.
2 µmol/kg (0.744 mg/kg) dose of MP-3180 by IV one time over 2 minutes.
4 µmol/kg (1.488 mg/kg) dose of MP-3180 by IV one time over 2 minutes.
1 µmol/kg (0.186 mg/kg) dose of MP-3180 by IV one time over 2 minutes.
Outcomes
Primary Outcome Measures
Total plasma clearance of MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. Total plasma clearance (the volume of plasma cleared of the drug over time) was calculated as: Clp = Dose/ AUC∞.
Renal clearance of MP-3180 and iohexol
Urine samples were collected pre-dose (time 0) and 5 mL urine samples were collected each time the subject voided.
The total volume of urine excreted was recorded until 12 hours post-dose, and analyzed using validated analytical methods. Renal clearance (the volume of plasma cleared of the drug by the kidneys over time) was calculated as: CLr
= Ae/ AUClast, where Ae is the cumulative amount of analyte excreted in urine over the sampling interval.
Maximum Plasma Concentration (Cmax) for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was directly determined from the concentration-time data.
Time to Maximum Plasma Concentration (Tmax) for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) was directly determined from the concentration-time data.
The terminal rate constant for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The terminal rate constant (λz) was determined by linear regression of the terminal linear phase of the log plasma concentration-time profile.
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng*hr/mL) was estimated from time 0 to the last measurable concentration using noncompartmental analyses.
Area under the plasma concentration-time curve from time zero to infinity for MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng*hr/mL) from time 0 to infinity was calculated as: AUC∞ = AUClast + LQC/λz where LQC is the predicted concentration (based on the terminal regression) at the time of the last measurable concentration.
The elimination half-life of MP-3180 and iohexol
Blood samples were collected and analyzed using validated analytical methods. The elimination half-life (the time required for the concentration of the drug to reach half of its original value) was calculated as t1/2 λz= ln(2)/ λz.
Secondary Outcome Measures
Incidence of adverse events
An adverse event (AE) was defined as any untoward medical occurrence in a study subject after study drug administration and that did not necessarily have a causal relationship with this treatment.
Number of laboratory values that fall outside of pre-specified normal ranges
Blood samples were collected and analyzed for hematology and clinical chemistry. Out of range values were documented.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02098187
Brief Title
Pharmacokinetics of MP-3180 and Use of Noninvasive Fluorescence Detection Device in Healthy Volunteers
Acronym
ORFM-1B
Official Title
Pilot 1B Study-Pharmacokinetics of MP-3180 and Use of Noninvasive Fluorescence Detection Device in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MediBeacon
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this early feasibility study was to investigate the pharmacokinetics of MP-3180 administered in rising doses and to evaluate the use of the Optical Renal Function Monitor (ORFM), an investigational noninvasive fluorescence detection device.
Detailed Description
This was an open-label, rising single-dose study to investigate the pharmacokinetics of the investigational agent, MP-3180, and to evaluate the use of the Optical Renal Function Monitor (ORFM), an investigational noninvasive fluorescence detection device. Single-dose pharmacokinetics at four dose levels were evaluated following the administration of a single, intravenous dose of MP-3180. Iohexol was also administered followed by saline. Prior to administration of MP-3180 and iohexol, ORFM sensor probes were affixed to four locations on the body of each participant. The noninvasive fluorescent signal from MP-3180 was measured using the ORFM investigational device continuously for approximately four hours post MP-3180 administration. For the determination of the pharmacokinetic disposition of MP-3180 and iohexol, blood samples were collected from each participant provided the individual completed all blood collections in the study. The pharmacokinetics of MP-3180 and iohexol were assessed by statistical comparison of pharmacokinetic parameters derived from plasma concentration-time curves and urine recovery data.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glomerular Filtration Rate, Acute Kidney Injury
Keywords
Glomerular Filtration Rate, Acute Kidney Injury
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Below target dose MP-3180
Arm Type
Active Comparator
Arm Description
0.5 µmol/kg (0.186 mg/kg) dose of MP-3180 by IV one time over 2 minutes.
Arm Title
2 times above target dose MP-3180
Arm Type
Active Comparator
Arm Description
2 µmol/kg (0.744 mg/kg) dose of MP-3180 by IV one time over 2 minutes.
Arm Title
4 times above target dose MP-3180
Arm Type
Active Comparator
Arm Description
4 µmol/kg (1.488 mg/kg) dose of MP-3180 by IV one time over 2 minutes.
Arm Title
At target dose MP-3180
Arm Type
Active Comparator
Arm Description
1 µmol/kg (0.186 mg/kg) dose of MP-3180 by IV one time over 2 minutes.
Intervention Type
Drug
Intervention Name(s)
Below target dose MP-3180
Intervention Description
MP-3180 0.5 µmol/kg (0.186 mg/kg) dose (fluorescent tracer agent) was administered by IV injection over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.
Intervention Type
Drug
Intervention Name(s)
At target dose MP-3180
Intervention Description
MP-3180 1 µmol/kg (0.186 mg/kg) dose (fluorescent tracer agent) was administered by IV injection over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.
Intervention Type
Drug
Intervention Name(s)
2 times above target dose MP-3180
Intervention Description
MP-3180 2 µmol/kg (0.744 mg/kg) dose (fluorescent tracer agent) was administered by IV injection over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.
Intervention Type
Drug
Intervention Name(s)
4 times above target dose MP-3180
Intervention Description
MP-3180 4 µmol/kg (1.488 mg/kg) dose (fluorescent tracer agent) was administered by IV injection over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.
Intervention Type
Device
Intervention Name(s)
ORFM prototype
Intervention Description
The Optical Renal Function Monitor (ORFM) investigational device noninvasively monitors fluorescent light emission from an exogenous tracer agent over time. Prior to administration of MP-3180 and iohexol, ORFM sensor probes were affixed to each of the participants via standard adhesive pads to four locations: forehead, sternum, upper inner arm, side trunk. The administration of the MP-3180 infusion and iohexol infusion occurred at least 15 minutes after the start of the data acquisition software.
Intervention Type
Other
Intervention Name(s)
Iohexol comparator
Intervention Description
Iohexol (Omnipaque 300, 5 mL) (comparator agent) was administered by IV injection over 2 minutes after MP-3180 injection, followed by a 10 mL saline flush IV over 2 minutes.
Primary Outcome Measure Information:
Title
Total plasma clearance of MP-3180 and iohexol
Description
Blood samples were collected and analyzed using validated analytical methods. Total plasma clearance (the volume of plasma cleared of the drug over time) was calculated as: Clp = Dose/ AUC∞.
Time Frame
Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Title
Renal clearance of MP-3180 and iohexol
Description
Urine samples were collected pre-dose (time 0) and 5 mL urine samples were collected each time the subject voided.
The total volume of urine excreted was recorded until 12 hours post-dose, and analyzed using validated analytical methods. Renal clearance (the volume of plasma cleared of the drug by the kidneys over time) was calculated as: CLr
= Ae/ AUClast, where Ae is the cumulative amount of analyte excreted in urine over the sampling interval.
Time Frame
60, 120, 240, 360, 600 and 720 minutes post-dose
Title
Maximum Plasma Concentration (Cmax) for MP-3180 and iohexol
Description
Blood samples were collected and analyzed using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was directly determined from the concentration-time data.
Time Frame
Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Title
Time to Maximum Plasma Concentration (Tmax) for MP-3180 and iohexol
Description
Blood samples were collected and analyzed using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) was directly determined from the concentration-time data.
Time Frame
Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Title
The terminal rate constant for MP-3180 and iohexol
Description
Blood samples were collected and analyzed using validated analytical methods. The terminal rate constant (λz) was determined by linear regression of the terminal linear phase of the log plasma concentration-time profile.
Time Frame
Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Title
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration for MP-3180 and iohexol
Description
Blood samples were collected and analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng*hr/mL) was estimated from time 0 to the last measurable concentration using noncompartmental analyses.
Time Frame
Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Title
Area under the plasma concentration-time curve from time zero to infinity for MP-3180 and iohexol
Description
Blood samples were collected and analyzed using validated analytical methods. The area under the plasma concentration-time curve (ng*hr/mL) from time 0 to infinity was calculated as: AUC∞ = AUClast + LQC/λz where LQC is the predicted concentration (based on the terminal regression) at the time of the last measurable concentration.
Time Frame
Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Title
The elimination half-life of MP-3180 and iohexol
Description
Blood samples were collected and analyzed using validated analytical methods. The elimination half-life (the time required for the concentration of the drug to reach half of its original value) was calculated as t1/2 λz= ln(2)/ λz.
Time Frame
Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
Secondary Outcome Measure Information:
Title
Incidence of adverse events
Description
An adverse event (AE) was defined as any untoward medical occurrence in a study subject after study drug administration and that did not necessarily have a causal relationship with this treatment.
Time Frame
1, 3, and 8 hours after dosing, and within 2 weeks after the final study dose
Title
Number of laboratory values that fall outside of pre-specified normal ranges
Description
Blood samples were collected and analyzed for hematology and clinical chemistry. Out of range values were documented.
Time Frame
Pre-dose and within 2 weeks after the final study dose
Other Pre-specified Outcome Measures:
Title
Correlation between MP-3180 fluorescence intensity and MP-3180 concentration in plasma
Description
Blood samples were collected and analyzed using validated analytical methods. The fluorescence intensity at the time of the blood sampling was compared to plasma concentrations.
Time Frame
Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age: 22 years of age or older
Sex: Males and not of childbearing potential females
Capable of informed consent
Weight restrictions:
at least 50 kg (110 lbs) for men
at least 48 kg (106 lbs) for women
all participants will have a Body Mass Index (BMI) less than or equal to 33 but greater than or equal to 19
All participants should be judged by the Principal Investigator or Medical Sub-Investigator physician as normal and healthy during a pre-study medical evaluation performed within 28 days of the initial dose of study medication
Exclusion Criteria:
Institutionalized participants will not be used
History of any significant cardiovascular disease, renal, pulmonary, hematologic, endocrine, immunologic, dermatologic, neurologic (including any history of seizure disorder), psychological, musculoskeletal disease or malignancies unless deemed not clinically significant by the Principal Investigator or Medical Sub-Investigator.
Donation or loss of blood or plasma: 50 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.
Intolerance to venipuncture.
Participants who have received an investigational drug within 30 days prior to the initial dose of study medication.
History of drug and/or alcohol abuse within the past year, unless currently enrolled in an abstinence program.
History of allergy or hypersensitivity to MP-3180 or iohexol, or other related 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 or Medical Sub-Investigator, could contraindicate the participant's participation in this study.
History of allergy or hypersensitivity to iodine containing contrast media or drugs.
Acute illness at the time of either the pre-study medical evaluation or dosing.
Social Habits:
Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication.
Ingestion of any vitamins or herbal supplement within 7 days prior to the initial dose of study medication.
Any significant change in dietary or exercise habits within the 48 hours prior to the initial dose of study medication.
Medications:
a. Use of any prescription or over-the-counter (OTC) medications within the 7 days prior to the initial dose of study medication.
Not within normal limits or clinically significant for lab testing; serum chemistries, hematology, urinalysis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard B. Dorshow, Ph.D.
Organizational Affiliation
MediBeacon, LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Pharmacokinetics of MP-3180 and Use of Noninvasive Fluorescence Detection Device in Healthy Volunteers
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