First in Human Study of RVP-001, a New Manganese Based MRI Contrast Agent

Study Overview
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Brief Summary
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The objectives of this trial are: To evaluate the safety and tolerability of single ascending doses of RVP-001 in healthy adult volunteers To determine the pharmacokinetics and elimination of RVP-001 in healthy adult volunteers.

Detailed Description
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The first in human study is intended to evaluate the safety and tolerability of single ascending doses of RVP-001 in healthy adult volunteers, and to determine the pharmacokinetics and elimination of RVP-001 in healthy adult volunteers.

Official Title
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A Single Center, Double-Blinded, Phase 1a Randomized Study to Evaluate Safety and Pharmacokinetics of a New Manganese Based Magnetic Resonance Imaging (MRI) Contrast Agent, RVP-001, in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: RVP-001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects Healthy subjects aged 18 to 55 years inclusive Suitable veins for phlebotomy, cannulation, or repeated venipuncture Have a body mass index between 18 and 32 kg/m^2 (inclusive); weigh at least 55 kg. Appropriately completed written informed consent prior to any study specific procedures. Exclusion Criteria: Any clinically significant abnormality or abnormal laboratory test results found during medical screening Vital sign abnormalities at screening or admission History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease; neurological or psychiatric disorder, as judged by the investigator Positive pregnancy test at screening or admission History of alcohol abuse History of drug abuse Use of nicotine-containing products within 12 months of study start Use of medication except topical products without significant systemic absorption Known allergies to any component of RVP-001 Subjects who have received any investigational product (IP) in a clinical research study within 5 IP half-lives or 30 days prior to first dose. Donation of plasma within 7 days prior to dosing; significant donation or loss of blood within 30 days prior to the first dosing. Any reason which, in the opinion of the Principal Investigator, would prevent the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RVP-001 group<br>4 Cohorts of 6 subjects each will receive RVP-001 at doses of 2, 4, 7 and 12 mg Mn/kg. | Drug: RVP-001<br>* Intravenous administration of RVP-001<br>* Other names: MnPyC3A;|
| Placebo Comparator: Placebo group<br>4 Cohorts of 2 subjects each will receive placebo (saline). | Drug: Placebo<br>* Intravenous administration of saline placebo<br>* Other names: saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter Cmax | Cmax = maximum observed blood plasma concentration of RVP-001 | pre-dose, 2, 5, 10, 20, 30 min and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post-dose | 
| PK Parameter Tmax | tmax = time of maximum observed plasma concentration of RVP-001 | pre-dose, 2, 5, 10, 20, 30 min and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post-dose | 
| PK Parameter t1/2 | t1/2 = terminal elimination half-life of RVP-001 | pre-dose, 2, 5, 10, 20, 30 min and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post-dose | 
| PK Parameter Cl | Cl = total body clearance calculated after a single IV administration of RVP-001 | pre-dose, 2, 5, 10, 20, 30 min and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post-dose | 
| PK Parameter Vd | Vd = volume of distribution calculated after a single IV administration of RVP-001 | pre-dose, 2, 5, 10, 20, 30 min and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| % RVP-001 Dose Excreted | mean % of RVP-001 excreted from urine from 0 -120 hours post dose | pre-dose, 2, 5, 10, 20, 30 min and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post-dose |