Yossi Gilgun-Sherki1, Rom E Eliaz2, David J McCann3, Pippa S Loupe4, Eli Eyal5, Kathleen Blatt6, Orit Cohen-Barak7, Hussein Hallak8, Nora Chiang9, Shwe Gyaw10. 1. Formerly Clinical Development & Medicine Section Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: ygilgun@gmail.com. 2. Formerly Innovative Project Leadership Research and Development Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: rom.eliaz@teva.co.il. 3. Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, MD, USA. Electronic address: DMCCANN@NIH.GOV. 4. Research and Scientific Affairs Research and Development Teva Pharmaceuticals, Overland Park, KS, USA. Electronic address: pippa.loupe@tevapharm.com. 5. Biostatistics Research and Development Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: eli.eyal@teva.co.il. 6. Global Clinical Operations Research and Development Teva Pharmaceuticals, Frazer, PA, USA. Electronic address: kathleen.blatt@tevapharm.com. 7. Phase 1 and Clinical Pharmacology Research and Development Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: orit.cohen-barak@teva.co.il. 8. Non-Clinical DMPK Research and Development Teva Pharmaceuticals, Petach Tikva, Israel. Electronic address: Hussein.Hallak@teva.co.il. 9. Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, MD, USA. Electronic address: nchiang@nida.nih.gov. 10. Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, MD, USA. Electronic address: shwe.gyaw@nih.gov.
Abstract
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.
RCT Entities:
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.
Authors: Brian Chan; Karli Kondo; Michele Freeman; Chelsea Ayers; Jessica Montgomery; Devan Kansagara Journal: J Gen Intern Med Date: 2019-06-10 Impact factor: 5.128