Clinical Phase III Study of SH/TA-508 as an Ultrasound Contrast Medium

—Effects on Transcranial Color Flow Imaging—

Abstract

A study to determine the safety and usefulness of a ultrasonic contrast agent SH/TA-508 was made at 11 institutions across the country in 108 patients who needed the diagnosis of cerebrovascular disorders by means of the transcranial Doppler method.
The patients first received SH/TA-508 in a volume of 5 ml at a concentration of 300 mg/ml. When the first dose failed to yield a good effect, they further received 4 ml at a concentration of 400 mg/ml as a second dose, followed by, if necessary, 10 ml at the concentration of 300 mg/ml or 8 ml at the concentration of 400 mg/ml. The signal enhancement was evaluated in four grades: - (no effect), + (poor), 2+ (adequate), and 3+ (excessive) . A response rate (the percentage of“2+”or more) was obtained in 79.0% with the first injection. The cumulative response rate with the second and the third injection amounted to 83.9% and 86.2%, respectively. The duration of the signal enhancement was assessed as “good” in 67.0% with the first injection, increasing to 78.5% after the second injection and to 83.9% after the third injection. In short, a good signal enhancement lasting long enough could be obtained with SH/TA-508 in an initial volume of 5 ml at a concentration of 300 mg/ml. When this first dose failed to yield a good effect, the signal enhancement was found improved to some extent with an additional 4 ml at a concentration of 400 mg/ml.
The diagnosis with the use of SH/TA-508 was assessed as “obviously improved” in 78.8%. Further, SH/TA-508 was assessed as safe in 92.3% of the patients as there were no serious side effects observed. One patient complained of malaise as a moderate side effect, but it was not a serious one and spontaneously disappeared without special treatment. This patient also suffered aggravation of liver function; as the causal association with SH/TA-508 could not be totally denied, the patient was classified into “safety questionable” in safety evaluation. There were several other patients who complained of pain or burning sensation; the incidence of side effects was eventually concluded as 7.7%.
Based on all of these results together, SH/TA-508 was concluded as either “very useful” or “useful” in 82.2%.
In conclusion, SH/TA-508 may be expected as a clinically useful ultrasonic contrast agent since the agent has no significant safety problem and may be expected to yield a good signal enhancement and a more reliable diagnosis when used in the transcranial Doppler method for cerebrovascular disorders.