Pharmacokinetics of MP-3180 and Use of Noninvasive Fluorescence Detection Device in Healthy Volunteers

NCT02098187 | Completed Phase 1 DMC

• 1 other identifier: ORFM-1B
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Glomerular Filtration Rate; Acute Kidney Injury

Keywords

Glomerular Filtration Rate; Acute Kidney Injury

Outcome Measures

Primary Outcomes (8)

• 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∞.

  Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose

• 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.

  60, 120, 240, 360, 600 and 720 minutes post-dose

• 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.

  Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose

• 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.

  Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose

• 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.

  Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose

• 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.

  Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose

• 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.

  Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose

• 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.

  Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose

Secondary Outcomes (2)

• Incidence of adverse events

  1, 3, and 8 hours after dosing, and within 2 weeks after the final study dose

• Number of laboratory values that fall outside of pre-specified normal ranges

  Pre-dose and within 2 weeks after the final study dose

Other Outcomes (1)

• Correlation between MP-3180 fluorescence intensity and MP-3180 concentration in plasma

  Pre-dose and 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 480 and 720 minutes post-dose

Study Arms (4)

Below target dose MP-3180

ACTIVE COMPARATOR

0.5 µmol/kg (0.186 mg/kg) dose of MP-3180 by IV one time over 2 minutes.

Drug: Below target dose MP-3180; Device: ORFM prototype; Other: Iohexol comparator

2 times above target dose MP-3180

ACTIVE COMPARATOR

2 µmol/kg (0.744 mg/kg) dose of MP-3180 by IV one time over 2 minutes.

Drug: 2 times above target dose MP-3180; Device: ORFM prototype; Other: Iohexol comparator

4 times above target dose MP-3180

ACTIVE COMPARATOR

4 µmol/kg (1.488 mg/kg) dose of MP-3180 by IV one time over 2 minutes.

Drug: 4 times above target dose MP-3180; Device: ORFM prototype; Other: Iohexol comparator

At target dose MP-3180

ACTIVE COMPARATOR

1 µmol/kg (0.186 mg/kg) dose of MP-3180 by IV one time over 2 minutes.

Drug: At target dose MP-3180; Device: ORFM prototype; Other: Iohexol comparator

Interventions

Below target dose MP-3180 DRUG

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.

Below target dose MP-3180

At target dose MP-3180 DRUG

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.

At target dose MP-3180

2 times above target dose MP-3180 DRUG

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.

2 times above target dose MP-3180

4 times above target dose MP-3180 DRUG

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.

4 times above target dose MP-3180

ORFM prototype DEVICE

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.

2 times above target dose MP-3180; 4 times above target dose MP-3180; At target dose MP-3180; Below target dose MP-3180

Iohexol comparator OTHER

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.

2 times above target dose MP-3180; 4 times above target dose MP-3180; At target dose MP-3180; Below target dose MP-3180

Eligibility Criteria

• Age: 22 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• MediBeacon: lead

Study Sites (1)

University of Maryland

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Richard B. Dorshow, Ph.D.

  MediBeacon, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: March 27, 2014
• Study Start: March 1, 2014
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: September 26, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)