title: Placebo-controlled evaluation of a bioengineered, cocaine-metabolizing fusion protein, TV-1380 (AlbuBChE), in the treatment of cocaine dependence.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Formerly Clinical Development & Medicine Section Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: ygilgun@gmail.com.
authors.forename: Yossi
authors.initials: Y
authors.lastname: Gilgun-Sherki
authors.affiliation: Formerly Innovative Project Leadership Research and Development Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: rom.eliaz@teva.co.il.
authors.forename: Rom E
authors.initials: RE
authors.lastname: Eliaz
authors.affiliation: Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, MD, USA. Electronic address: DMCCANN@NIH.GOV.
authors.forename: David J
authors.initials: DJ
authors.lastname: McCann
authors.affiliation: Research and Scientific Affairs Research and Development Teva Pharmaceuticals, Overland Park, KS, USA. Electronic address: pippa.loupe@tevapharm.com.
authors.forename: Pippa S
authors.initials: PS
authors.lastname: Loupe
authors.affiliation: Biostatistics Research and Development Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: eli.eyal@teva.co.il.
authors.forename: Eli
authors.initials: E
authors.lastname: Eyal
authors.affiliation: Global Clinical Operations Research and Development Teva Pharmaceuticals, Frazer, PA, USA. Electronic address: kathleen.blatt@tevapharm.com.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Blatt
authors.affiliation: Phase 1 and Clinical Pharmacology Research and Development Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: orit.cohen-barak@teva.co.il.
authors.forename: Orit
authors.initials: O
authors.lastname: Cohen-Barak
authors.affiliation: Non-Clinical DMPK Research and Development Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: Hussein.Hallak@teva.co.il.
authors.forename: Hussein
authors.initials: H
authors.lastname: Hallak
authors.affiliation: Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, MD, USA. Electronic address: nchiang@nida.nih.gov.
authors.forename: Nora
authors.initials: N
authors.lastname: Chiang
authors.affiliation: Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, MD, USA. Electronic address: shwe.gyaw@nih.gov.
authors.forename: Shwe
authors.initials: S
authors.lastname: Gyaw
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000008:administration & dosage*; D057005:Bioengineering / Q000379:methods; D002091:Butyrylcholinesterase / Q000008:administration & dosage*; D003042:Cocaine / Q000378:metabolism*; D019970:Cocaine-Related Disorders / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects / Q000502:physiology; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000418:Albumins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C000604228:TV-1380; D002091:Butyrylcholinesterase; D003042:Cocaine
keywords: Addiction; AlbuBChE; Butyrylcholinesterase; Cocaine; Dependence; TV-1380