Placebo-controlled evaluation of a bioengineered, cocaine-metabolizing fusion protein, TV-1380 (AlbuBChE), in the treatment of cocaine dependence.

Drug Alcohol Depend 2016 Sep 28;166:13-20. Epub 2016 May 28.

Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, MD, USA. Electronic address:

Background: TV-1380 (AlbuChE) is a novel recombinant fusion protein of mutated butyrylcholinesterase (BChE) that has increased catalytic efficiency for cocaine metabolism compared to wild-type BChE.

Methods: Intra-muscular injections of TV-1380 (150mg or 300mg) or placebo were administered once weekly to participants (n=66-69 per group) in a randomized, double-blind study to evaluate the ability of TV-1380 to facilitate abstinence in treatment-seeking, cocaine-dependent individuals. The primary endpoint was the proportion of participants achieving abstinence from cocaine during the last three weeks of the 12 week treatment phase, based on daily self-report of "no use" confirmed by urine testing.

Results: Although there were no significant differences between the TV-1380 treatment groups and placebo for the primary endpoint, 6% of participants in the 150mg and 300mg TV-1380 groups and no participants in the placebo group achieved abstinence. For the only declared secondary endpoint, there was a dose-dependent increase in the group mean percentage of urine samples testing negative for cocaine metabolites during weeks 5-12 (8.1% and 14.6% for the 150mg and 300mg TV-1380 groups, respectively, compared to 4.7% for the placebo group; p=0.0056 for 300mg vs. placebo). No meaningful differences in adverse events were seen between treatment groups.

Conclusions: While the apparent reduction in cocaine use may be of insufficient magnitude to justify further trials of TV-1380 in cocaine dependence, the results argue for development of improved enzymes with greater catalytic activity.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.drugalcdep.2016.05.019DOI Listing
September 2016
23 Reads

Publication Analysis

Top Keywords

150mg 300mg
12
tv-1380
8
fusion protein
8
300mg tv-1380
8
placebo group
8
cocaine dependence
8
300mg placebo
8
tv-1380 groups
8
primary endpoint
8
cocaine
6
placebo
5
secondary endpoint
4
declared secondary
4
placebo primary
4
groups placebo
4
tv-1380 treatment
4
treatment groups
4
group achieved
4
differences tv-1380
4
groups participants
4

Altmetric Statistics

Similar Publications