An Ascending Dose Comparison of MVT-100 to Definity in Healthy Volunteers

Microvascular Therapeutics, LLC16 enrolled

Overview

Definity (perflutren lipid microspheres, Lantheus Medical Imaging) is an ultrasound contrast indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border. MVT-100 (the investigational pharmaceutical) is similar to Definity, with the exception of the removal of one lipid in the lipid blend and substitution of another lipid. This study is intended to evaluate the safety and efficacy of MVT-100 using a single ascending dose design in healthy volunteers. Patients are randomized to receive either MVT-100 or Definity and undergo echocardiograms after receiving either MVT-100 or Definity via bolus or IV infusion administration. The primary endpoints evaluated are safety and endocardial border delineation.

Ultrasound is one of the most common imaging examinations and has advantages of absence of ionizing radiation, portability and relatively low cost. Ultrasound contrast agents are used to improve the accuracy of ultrasound and Definity (perflutren) is the world's leading ultrasound contrast agent but perflutren has to be refrigerated and has a side effect of back pain. The investigators have developed a new, improved perflutren, MVT-100, with potential for room temperature storage. Ultrasound contrast agents are used to increase the backscatter (signal intensity of blood vessels and tissues to improve diagnostic accuracy) of ultrasound imaging. In the US ultrasound contrast agents are FDA approved for echocardiography to improve endomyocardial border definition. MVT-100 reflects the ultrasound to provide strong back-scattering. MVT-100 microbubbles resonate with ultrasound to provide strong harmonic signals. MVT-100 microbubbles will cavitate with higher levels of ultrasound and cavitation may be stable or inertial depending upon acoustic parameters and other factors. The study is a multi centre ascending dose comparison of Definity and MVT-100 for use in echocardiography and will be performed in a sample of healthy volunteers who are randomized to receive either Definity or MVT-100. This trial will assess safety and evaluate the following imaging metrics: * Determine the optimal dose of MVT-100 by comparing MVT-100 vs Definity in the change from baseline of quantitative left ventricular opacification * Evaluation of qualitative left ventricular opacification (LVO) * Evaluation of endocardial border delineation * Evaluation of endocardial border length * Evaluation of duration of useful contrast

Study Type

INTERVENTIONAL

Interventions

EchocardiogramDIAGNOSTIC_TEST

Images will be recorded in parasternal long, short axis, apical four, two, and three chamber views according to the American Society of Echocardiography (ASE) 17 segment model. Each assessment will include one round of low MI imaging (\<0.3) and one round of very low MI imaging (\<0.2) in each of the pre-specified windows according to the 2014 ASE Sonographer Guidelines. A baseline echocardiogram will be performed prior to the administration of DEFINITY® or MVT-100. Assessments will be made three times, once from 0 - 1 ½ minutes following injection, once between 1 ½ minutes to 3 minutes following IV injection and once from 3 - 4 ½ minutes following IV injection. Assessments at each time point will include one round of low MI imaging (\<0.3) and one round of very low MI imaging (\<0.2). Each round will include the views in the following order: parasternal long, parasternal short, apical 4, apical 2 and apical 3.

MVT-100DRUG

After randomization, MVT-100, the experimental drug, is administered via IV infusion or bolus administration and echocardiograms are subsequently obtained.

DefinityDRUG

After randomization, Definity, the active comparator, is administered via IV infusion or bolus administration and echocardiograms are subsequently obtained.

Eligibility

Sex: ALLMin age: 19 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Adult subjects 19 years of age or older, male or female * Female subjects must no longer have child-bearing potential (\>1-year post menopause or surgically sterilized), or must * have a negative urine pregnancy test, and * be using and continue to use for 30 days after the study a medically effective method of contraception * Adequate hematologic, renal and hepatic function, as defined by: * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L * Hemoglobin ≥ 90 g/L * Plasma creatinine\< 1.5 x ULN * Total bilirubin within normal limits (\< 2.5 x ULN if Gilbert's syndrome) * Aspartate transaminase (AST) and Alanine transaminase (ALT) \< 2.5 x ULN * Subject must be willing and able to understand the study and provide written Informed Consent to participate in the study Exclusion Criteria: * Myocardial infarction within six months prior to enrollment * Unstable angina, NYHA Class II or greater congestive heart failure * EKG evidence of uncontrolled arrhythmia or history of clinically significant arrhythmia within the past six months * Clinically significant Chronic Obstructive Pulmonary Disease (COPD) or other pulmonary condition that is not controlled by medication or requires oxygen frequently or continuously * A history of pulmonary emboli * Known hypersensitivity to perflutren, DEFINITY® or other echo contrast agent * Inability to remain supine for 60 minutes * Oxygen saturation \< 95% on room air * History of allergic reaction attributed to compounds of similar chemical composition to MVT-100 or DEFINITY® or soy or egg allergies (see Investigator's Brochure) * Subject has received any investigational drug within thirty (30) days prior to enrollment into the study * Inability to comply with study procedures * Subjects with any medical condition deemed by the investigator to make the subject inappropriate for participation

Outcomes

Primary Outcomes

QT Interval

The null hypothesis for safety (H0) will be: MVT-100 is not as safe as DEFINITY®. The alternative hypothesis (HA) for safety will be: MVT-100 is equivalent to, or safer than, DEFINITY®. Specifically, the following hypotheses will be tested: HA: Δ2min QT interval EKG(MVT-100) ≤ Δ2min QT interval EKG(Definity®) HA: Δ2min Blood Pressure(MVT-100) ≤ Δ2min Blood Pressure(Definity®) HA: Δ2min Heart Rate(MVT-100) ≤ Δ2min Heart Rate(Definity®) HA: Δ2min O2(MVT-100) ≤ Δ2min O2(Definity®) HA: Other Symptom(2min post MVT-100) ≤ Other Symptom(2min post Definity®)

Time frame: Day of study

Blood Pressure

Time frame: Day of study

Heart Rate

Time frame: Day of study

Oxygen Saturation

Time frame: Day of study

Other Symptoms

Time frame: Day of study

Secondary Outcomes

Left Ventricular Opacification (LVO)

The null hypothesis for efficacy (H0) will be: MVT-100 is not as effective as DEFINITY®. The alternative hypothesis (HA) for efficacy will be: MVT-100 is equivalently or more effective than DEFINITY®. Specifically, the following hypotheses will be tested: HA: LVO(MVT-100) ≥ LVO(Definity®) HA: SegmentVisualization(MVT-100) ≥ SegmentVisualization(Definity®)

Time frame: Day of Study

Cardiac Segment Visualization

Time frame: Day of Study

An Ascending Dose Comparison of MVT-100 to Definity in Healthy Volunteers

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes