Study to Evaluate Safety, Tolerability, and Pharmacokinetics (PK) of Intravenous (IV) Infusion of MTP-131 (Bendavia™) in Healthy Adults

Study Overview
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Brief Summary
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This is the first study of MTP-131 (Bendavia™) in humans. The objective of this study is to evaluate the safety, tolerability, and pharmacokinetics of escalating single intravenous infusion doses of MTP-131.

Detailed Description
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The primary objective of the study is to evaluate the safety and tolerability of MTP-131 in healthy volunteers following a single intravenous infusion. The secondary objective is to evaluate the pharmacokinetics of MTP-131. This is a double-blind, placebo-controlled, randomized trial. A total of 40 eligible subjects will be enrolled and randomized in a 3:1 active to placebo ratio for a total of 5 treatment groups of 8 volunteers. As far as is logistically possible, each treatment group will have similar numbers of male and female volunteers. After the last subject for each cohort has completed the day 3 clinical assessment and no stopping rules have been met according to Safety Review Board decision, the next cohort will commence.

Official Title
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A Phase I Study in Healthy Male and Healthy Female Subjects to Characterize the Safety, Tolerability, and Pharmacokinetics of Intravenous Infusion of MTP-131 (Bendavia™) Using a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Design

Conditions
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Healthy

Intervention / Treatment
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* Drug: MTP-131 (Bendavia™)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult males or females age ≥18 years of age with signed informed consent. Women who are not post-menopausal or surgically sterile must have a negative serum pregnancy test at screening and within 24 hours of treatment and who agree to use effective contraception for 30 days following the study. Exclusion Criteria: Clinically significant laboratory abnormalities, Clinically significant abnormalities on physical examination, BMI of less than 18 kg/m2 or greater than 32 kg/m2, Any disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including an ulcer) systems, History of seizures or epilepsy, History of serious mental illness, Participant in unrelated research involving investigational product within 30 days before planned date of drug administration, Positive serology for HIV 1, HIV 2, HBsAg, or HCV, Fever greater than 37.5°C at the time of planned dosing, Suspicion of or recent history of alcohol or substance abuse, Donated blood or blood products within the past 30 days, Women who are pregnant or breastfeeding, Employee or family member of the investigational site, and Subjects who currently smoke cigarettes, cigars, pipes or chew tobacco products, Subjects who are either unwilling to agree to refrain from use or found to be using: Alcohol, caffeine, xanthine-containing food or beverages, nicotine products and over-the-counter medications with the exception of Tylenol from 24 hours prior to dosing and throughout the confinement period Prescription medications from 14 days prior to and 7 days post treatment Oral contraceptives without concomitant use of double-barrier contraceptives (condom, diaphragm with spermicide) for a period of 7 days prior to and 30 days post treatment

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Cohort 1, Dose 0.010 mg/kg/hr Active (6), Placebo (2), Total Subjects (8) | Drug: MTP-131 (Bendavia™)<br>* Single 4 hour intravenous infusion<br>|
| Experimental: Arm 2<br>Cohort 2, Dose 0.025 mg/kg/hr Active (6), Placebo (2), Total Subjects (8) | Drug: MTP-131 (Bendavia™)<br>* Single 4 hour intravenous infusion<br>|
| Experimental: Arm 3<br>Cohort 3, Dose 0.050 mg/kg/hr Active (6), Placebo (2), Total Subjects (8) | Drug: MTP-131 (Bendavia™)<br>* Single 4 hour intravenous infusion<br>|
| Experimental: Arm 4<br>Cohort 4, Dose 0.100 mg/kg/hr Active (6), Placebo (2), Total Subjects (8) | Drug: MTP-131 (Bendavia™)<br>* Single 4 hour intravenous infusion<br>|
| Experimental: Arm 5<br>Cohort 5, Dose 0.250 mg/kg/hr Active (6), Placebo (2), Total Subjects (8) | Drug: MTP-131 (Bendavia™)<br>* Single 4 hour intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment emergent adverse events in treatment group versus placebo group | Safety assessments including vital signs, physical exam,12-lead ECG, serum chemistry, hematology, and urinalysis will be collected the day prior to and for 7 days following study drug infusion. These parameters will be assessed for clinically significant abnormalities. | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of MTP-131 including Css, Cmax, tmax, t½, AUC and dose proportionality. | Css (plasma steady state concentration), Cmax (observed peak plasma concentration), tmax (time of observed peak), AUC0-t (area under the plasma concentration time curve from time zero to the last quantifiable timepoint), AUC0-∞ (area under the plasma concentration time curve from time zero to infinity), λz (terminal [or elimination rate] phase rate constant), t½ (terminal half-life), CL (plasma clearance) and Vss (volume of distribution at steady state) will be determined for MTP-131. Ae (amount excreted in the urine) and CLr (renal clearance) may also be evaluated. | Pre-infusion through 32 hours post infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Safety, Clinical Trial, Phase I, Nontherapeutic Human Experimentation, Heading Pharmacokinetics, Phase I Safety and Tolerability