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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: MTP-131 (Bendavia™)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014-3616
      • Clinical Pharmacology of Miami, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. 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
  2. Prescription medications from 14 days prior to and 7 days post treatment
  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stealth BioTherapeutics Inc.
• Investigators: Principal Investigator: Kenneth Lasseter, MD, Clinical Pharmacology of Miami, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: April 30, 2010
• First Submitted That Met QC Criteria: May 3, 2010
• First Posted (Estimate): May 4, 2010

Study Record Updates

• Last Update Posted (Estimate): November 18, 2010
• Last Update Submitted That Met QC Criteria: November 17, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Drug Safety; Clinical Trial, Phase I; Nontherapeutic Human Experimentation; Heading Pharmacokinetics; Phase I Safety and Tolerability
• Other Study ID Numbers: SPIRI-101