Pharmacokinetics of MP-3180 in Healthy Volunteers

NCT02098174 | Completed Phase 1 DMC

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

Brief Summary

The purpose of this study was to investigate the pharmacokinetics of MP-3180 (1 µmol/kg) compared to the pharmacokinetics of iohexol (5 mL of a 300 mg iodine (I)/mL solution) in healthy adult participants. The secondary objective was to evaluate the safety and tolerability of MP-3180 in healthy adult participants.

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 the following times after dosing: 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.

  Pre-dose and each time the participant voided up to 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 the following times after dosing: 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 the following times after dosing: 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 the following times after dosing: 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 the following times after dosing: 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 the following times after dosing: 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 the following times after dosing: 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 the plasma clearance of MP-3180 and the plasma clearance of iohexol

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

Study Arms (1)

Healthy participants

EXPERIMENTAL

MP-3180 (1 µmol/kg or 0.372 mg/kg) was administered by IV injection (2.5 mL to 3.5 mL for participant weights of 70 kg to 91 kg) over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes. The iohexol comparator (Omnipaque 300, 5 mL) was then administered by IV injection over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.

Drug: MP-3180; Other: Iohexol comparator

Interventions

MP-3180 DRUG

MP-3180 (1 µmol/kg or 0.372 mg/kg) (fluorescent tracer agent) was administered by IV injection (2.5 mL to 3.5 mL for participant weights of 70 kg to 91 kg) over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.

Healthy participants

Iohexol comparator OTHER

Iohexol (Omnipaque 300, 5 mL) was administered by IV injection over 2 minutes, followed by a 10 mL saline flush IV over 2 minutes.

Healthy participants

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:
• a. at least 50 kg (110 lbs) for men
• b. at least 48 kg (106 lbs) for women
• c. 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
• \. Social habits:
• a. Ingestion of any alcoholic, caffeine- or xanthine-containing food or beverage within the 48 hours prior to the initial dose of study medication.
• b. Ingestion of any vitamins or herbal supplement within 7 day prior to the initial dose of study medication.
• c. Any significant change in dietary or exercise habits within the 48 hours prior to the initial dose of study medication.
• d. History of drug and/or alcohol abuse within the past year, unless currently enrolled in an abstinence program.
• \. Use of any prescription or over-the-counter (OTC) medications within the 7 days prior to the initial dose of study medication.
• \. 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.
• \. Acute illness at the time of either the pre-study medical evaluation or dosing.
• \. Not within normal limits or clinically significant for lab testing
• \. Any reason which, in the opinion of the Principal Investigator or Medical Sub-Investigator, would prevent the participant from safely participating in the study.
• \. 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 allergy or hypersensitivity to MP-3180 or iohexol, or other related products, or any of the inactive ingredients.

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

• Thomas Dowling, Ph.D.

  University of Maryland

  PRINCIPAL INVESTIGATOR

• Richard B. Dorshow, Ph.D.

  MediBeacon, LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 21, 2014
• First Posted: March 27, 2014
• Study Start: November 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: September 23, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)