A Study to Evaluate Pharmacokinetics of Sonazoid™ Following Intravenous Bolus Injection in Healthy Volunteers

Study Overview
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Brief Summary
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The primary purpose of this study is to determine the Pharmacokinetics (PK) data of perfluorobutane (PFB) in blood and exhaled air following intravenous (I.V.) bolus injection of Sonazoid™ in healthy volunteers.

Official Title
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Pharmacokinetics of Sonazoid™ Following Intravenous Bolus Injection in Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: Sonazoid™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants may be included in the study if they meet all of the following criteria: Participant is between 18 and 45 years of age Participant is male, or a female who was either surgically sterile (has a documented bilateral oophorectomy and/or documented hysterectomy), postmenopausal (cessation of menses for more than 1 year), or non-lactating, or if of childbearing potential the results of a serum or urine human chorionic gonadotropin pregnancy test, performed on the day of Sonazoid™ administration (with the result known before IMP administration), were negative Participant is able and willing to comply with study procedures and provide signed and dated informed consent Participant has a body mass index of 19 to 26 Participant has agreed not to smoke from 2 hours before to 5 hours after Sonazoid™ administration Participant has agreed to avoid strenuous physical activity from 1 week before Sonazoid™ administration until the end of the study follow-up Participant has no history of alcohol or substance abuse, and has agreed to no intake of alcohol or drugs for 48 hours before Sonazoid™ administration and until the end of the study follow-up Participant has a normal health status, as judged by medical history and physical examination at screening Normal 12-lead electrocardiogram (ECG) at screening. Minor abnormalities considered by the investigator to be of no clinical importance are permitted Normal blood and urine clinical chemistry variables at screening. Isolated or minimally out-of-range values considered by the investigator to be of no clinical importance are permitted No regular use of concomitant medication, except for routine use of supplemental oestrogen Exclusion Criteria: Participant was previously included in this study Participation in another clinical trial with an unregistered medicinal product, or less than 30 days have passed since completing participation in such a trial Participant has a history of allergies to eggs or egg products (i.e., manifested by full body rash, respiratory difficulty, oral and laryngeal swelling, hypotension or shock) Donation of >500 milliliter (mL) blood in the 12 weeks before Sonazoid™ administration Participant with congenital heart defects, including right-to-left, bi-directional, or transient right-to-left cardiac shunts Participant has positive test results for hepatitis B, hepatitis C, or human immunodeficiency virus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sonazoid™ 0.12 microliter (µl)<br>Participants will receive single intravenous (I.V) bolus injection of Sonazoid™ 0.12 µl microbubbles (MB)/kilogram (kg) body weight. | Drug: Sonazoid™<br>* Single Dose of Sonazoid™ lipid-stabilised aqueous suspension of perfluorobutane (PFB) gas microbubbles.<br>* Other names: perfluorobutane;|
| Experimental: Sonazoid™ 0.60 µl<br>Participants will receive single I.V bolus injection of Sonazoid™ 0.60 µl MB/kg body weight. | Drug: Sonazoid™<br>* Single Dose of Sonazoid™ lipid-stabilised aqueous suspension of perfluorobutane (PFB) gas microbubbles.<br>* Other names: perfluorobutane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration Versus Time Curve from Time Zero to the Last Time- Point (AUC 0-last), AUC from Time Zero to Infinity (AUC0-infinity∞) After Single Dose in Blood |  | Pre dose and at 0.5, 1, 2, 5, 10, 15, 30, 60, 120 minutes and 4 hours post dose | 
| Area Under the Concentration Versus Time Curve from Time Zero to the Last Time- Point (AUC 0-last), AUC from Time Zero to Infinity (AUC0-Infinity∞) After Single Dose in Exhaled Air |  | Pre dose and at 1, 3, 6, 9, 16, 31, 61, 121 minutes and 4 hours post dose | 
| Percentage of the Extrapolated Area to Total Area (% AUC ext) After Single Dose in Blood |  | Pre dose and at 0.5, 1, 2, 5, 10, 15, 30, 60, 120 minutes and 4 hours post dose | 
| Percentage of the Extrapolated Area to Total Area (% AUC ext) After Single Dose in Exhaled Air |  | Pre dose and at 1, 3, 6, 9, 16, 31, 61, 121 minutes and 4 hours post dose | 
| Elimination Rate Constant (kel) in Blood |  | Pre dose and at 0.5, 1, 2, 5, 10, 15, 30, 60, 120 minutes and 4 hours post dose | 
| Elimination Rate Constant (kel) in Exhaled Air |  | Pre dose and at 1, 3, 6, 9, 16, 31, 61, 121 minutes and 4 hours post dose | 
| Elimination Half-life (t½) in Blood |  | Pre dose and at 0.5, 1, 2, 5, 10, 15, 30, 60, 120 minutes and 4 hours post dose | 
| Elimination Half-life (t½) in Exhaled Air |  | Pre dose and at 1, 3, 6, 9, 16, 31, 61, 121 minutes and 4 hours post dose | 
| Clearance (Cl) in Blood |  | Pre dose and at 0.5, 1, 2, 5, 10, 15, 30, 60, 120 minutes and 4 hours post dose | 
| Clearance (Cl) in Exhaled Air |  | Pre dose and at 1, 3, 6, 9, 16, 31, 61, 121 minutes and 4 hours post dose | 
| Maximum Observed Concentration (Cmax) in Blood |  | Pre dose and at 0.5, 1, 2, 5, 10, 15, 30, 60, 120 minutes and 4 hours post dose | 
| Maximum Observed Concentration (Cmax) in Exhaled Air |  | Pre dose and at 1, 3, 6, 9, 16, 31, 61, 121 minutes and 4 hours post dose | 
| Time at which Cmax is reached (tmax) in Blood |  | Pre dose and at 0.5, 1, 2, 5, 10, 15, 30, 60, 120 minutes and 4 hours post dose | 
| Time at which Cmax is reached (tmax) in Exhaled Air |  | Pre dose and at 1, 3, 6, 9, 16, 31, 61, 121 minutes and 4 hours post dose | 
| Volume of Distribution (Vd) in Blood |  | Pre dose and at 0.5, 1, 2, 5, 10, 15, 30, 60, 120 minutes and 4 hours post dose | 
| Volume of Distribution (Vd) in Exhaled Air |  | Pre dose and at 1, 3, 6, 9, 16, 31, 61, 121 minutes and 4 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Related Adverse Events (AEs) |  | Up to 72 hours after first administration of investigational medicinal product (IMP) | 
| Percentage of Participants With Abnormal Laboratory Values |  | Up to 4 hours post dose | 
| Percentage of Participants With Abnormal Vital Signs |  | Up to 4 hours post dose | 
| Percentage of Participants With Injection Site Reactions |  | Up to 4 hours post dose | 
| Percentage of Participants With Abnormal Physical Examinations |  | Up to 4 hours post dose |