A phase I single blind clinical trial of a new oxygen transport agent (MP4), human hemoglobin modified with maleimide-activated polyethylene glycol

Abstract

BACKGROUND AND OBJECTIVES: MP4 (Hemospan), a hemoglobin-based oxygen carrier, has been designed to deliver oxygen to hypoxic tissues without causing vasoconstriction. A phase I clinical trial of MP4 was undertaken to evaluate whether MP4 elicits the clinical side effects associated with previous hemoglobin-based solutions. DESIGN AND METHODS: Twelve volunteers were studied. One cohort (n=4) received 50 mg/kg of MP4, a second (n=4) received 100 mg/kg of MP4, and the third (n=4) received lactated Ringer's solution. Single blind infusions were given at 5 mL/min. Vital signs and symptoms, hematologic parameters, serum chemistry, renal and electrocardiographic measurements were monitored for 15 days after dosing. RESULTS: Five mild adverse events occurred in the controls and 2 each in the 50 mg/kg and 100 mg/kg MP4 groups. None was severe or judged related to MP4 administration by the principal investigator. There were no clinically significant alterations in blood pressure or heart rate, and there were no gastrointestinal symptoms, abdominal or flank pain, loss of appetite or clinically significant alterations of liver or pancreatic enzymes. In one subject (100 mg/kg of MP4), amylase and lipase were slightly above the upper limit of normal 4 hours after dosing, but without associated symptoms or signs. Pharmacokinetic analysis of plasma hemoglobin (assuming no hemolysis) yielded an estimated half-life (T1/2) of 43 hours in the 100 mg/kg MP4 subjects. INTERPRETATION AND CONCLUSIONS: MP4 appears to have a favorable safety profile. Subjects in both study groups survived and did no less well than those in the control group.