The main goal of this Project is to determine if there is any toxicity resulting from either single of repeated intravenous infusion of human monoclonal anti-cocaine antibody (mACAb) when administered to normal volunteers. Additional goals are to study the pharmacokinetic properties of the mACAb and to establish whether the subjects produce anti-idiotypic and anti-isotypic antibodies in response to the infusion. The subjects will initially be dosed at sufficiently low levels of mACAb that adverse events will be very unlikely. The highest dose is chosen at such a level that when given to cocaine abusers it will sequester about 40 mg of cocaine, an amount that we feel would be of therapeutic significance. Subjects: Study-1: A total of 24 normal male of female volunteers (eight to be infused with placebo and 16 with various doses of the mACAb) who satisfy the study criteria will be brought into the hospital for infusion and post-infusion medical evaluation. They will be followed as outpatients for a period of three half lives of the medication (T/1/2 will be approximately three weeks). Study-2: A new set of 64 individuals will be recruited for the multiple dosing study. For each dose level eight subjects will be randomized to placebo and eight to the monoclonal antibody. Procedures: All subjects will be evaluated medically during screening and periodically during the inpatient and outpatient study period for signals of toxicity, and for the production of anti-idiotypic and anti-isotypic antibodies. In addition, there will be scheduled blood draws for determining the pharmacokinetic parameters for the monoclonal antibody. Each study will being with a one week placebo washout period. Subjects without measurable deterioration in health will be randomized to the mACAb or to placebo. Four doses of the mACAb will be utilized (10 mg, 100 mg, 1g, and 10 g). Measures and analysis: Various clinical parameters will be monitored. Changes between placebo and antibody-infused subjects will be compared to determine the safety of mACAb in single and repeated doses. The concentration of the monoclonal antibody will be measured as a function of time. The area under the curve from prior to infusion to three half-lives after (or to the limits of detectibility) will be calculated.
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