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A Randomized, Double-blind, Placebo-Controlled Efficacy Trial

Bridget A. Martell, MD, MA; Frank M. Orson, MD; James Poling, PhD; Ellen Mitchell, RN; Roger D. Rossen, MD; Tracie Gardner, PhD; Thomas R. Kosten, MD

Arch Gen Psychiatry. 2009;66(10):1116-1123.

Context  Cocaine dependence, which affects 2.5 million Americans annually, has no US Food and Drug Administration–approved pharmacotherapy.

Objectives  To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence.

Design  A 24-week, phase 2b, randomized, double-blind, placebo-controlled trial with efficacy assessed during weeks 8 to 20 and follow-up to week 24.

Setting  Cocaine- and opioid-dependent persons recruited from October 2003 to April 2005 from greater New Haven, Connecticut.

Participants  One hundred fifteen methadone-maintained subjects (67% male, 87% white, aged 18-46 years) were randomized to vaccine or placebo, and 94 subjects (82%) completed the trial. Most smoked crack cocaine along with using marijuana (18%), alcohol (10%), and nonprescription opioids (44%).

Intervention  Over 12 weeks, 109 of 115 subjects received 5 vaccinations of placebo or succinylnorcocaine linked to recombinant cholera toxin B-subunit protein.

Main Outcome Measure  Semiquantitative urinary cocaine metabolite levels measured thrice weekly with a positive cutoff of 300 ng/mL.

Results  The 21 vaccinated subjects (38%) who attained serum IgG anticocaine antibody levels of 43 µg/mL or higher (ie, high IgG level) had significantly more cocaine-free urine samples than those with levels less than 43 µg/mL (ie, low IgG level) and the placebo-receiving subjects during weeks 9 to 16 (45% vs 35% cocaine-free urine samples, respectively). The proportion of subjects having a 50% reduction in cocaine use was significantly greater in the subjects with a high IgG level than in subjects with a low IgG level (53% of subjects vs 23% of subjects, respectively) (P = .048). The most common adverse effects were injection site induration and tenderness. There were no treatment-related serious adverse events, withdrawals, or deaths.

Conclusions  Attaining high (43 µg/mL) IgG anticocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated subjects attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters.

Trial Registration  clinicaltrials.gov Identifier: NCT00142857

Author Affiliations: Departments of Medicine (Dr Martell) and Psychiatry (Dr Poling and Ms Mitchell), Yale University School of Medicine, New Haven, and Veterans Affairs Connecticut Healthcare System, West Haven (Drs Martell and Poling and Ms Mitchell); and Departments of Medicine and Immunology (Drs Orson and Rossen) and Menninger Department of Psychiatry and Behavioral Sciences (Drs Gardner and Kosten), Baylor College of Medicine, and Michael E. DeBakey Veterans Affairs Medical Center (Drs Orson, Rossen, Gardner, and Kosten), Houston, Texas.

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