Search

UNLABELLED Cocaine dependence presents a major public health issue, and to date, no pharmacotherapies are approved for its treatment. TV-1380 is a novel recombinant albumin-fused mutated butyrylcholinesterase (Albu-BChE) that has increased catalytic efficiency for cocaine compared with wild-type BChE and therefore has the potential to facilitate abstinence in cocaine-dependent subjects by decreasing exposure to cocaine and its reinforcing effects. METHODS This randomized, double-blind, placebo-controlled, parallel-group study in nondependent cocaine users was conducted to evaluate the effect of a single intramuscular dose of Albu-BChE (50, 100, and 300 mg) on the pharmacokinetic and metabolic profile of intravenous cocaine infusions (40 mg) administered at baseline and at 24, 96, and 168 hours after Albu-BChE dosing, to assess safety of coadministering Albu-BChE and cocaine, and to explore the subjective responses to cocaine infusions after Albu-BChE dosing. RESULTS Administration of Albu-BChE resulted in significant dose-dependent reductions in cocaine exposure (maximum concentration, area under the curve) and half-life. Effects were greatest at 24 hours after Albu-BChE dose, but were sustained up to 168 hours. Spearman correlations indicated a significant negative relationship between Albu-BChE concentration and cocaine clearance and exposure. Consistent with its mechanism of action, Albu-BChE also shifted cocaine metabolism toward preferential formation of ecgonine methyl ester. Administration of Albu-BChE was associated with modest decreases in subjective reports of feeling high and willingness to take cocaine again after cocaine infusion. Coadministration of Albu-BChE and cocaine was safe and well tolerated. CONCLUSIONS Administration of Albu-BChE at single doses of 50, 100, and 300 mg safely resulted in long-lasting decreases in cocaine exposure in recreational cocaine users.

The etiologies of functional dyspepsia (FD) are unclear, but in some studies, treatment with a proton pump inhibitor has been beneficial. The objective of this study was to evaluate the efficacy of esomeprazole 40 mg once a day compared to placebo in achieving symptom relief in primary care patients with FD.This was a randomized, placebo-controlled trial in adult FD patients, who had at least moderate severity of symptoms, defined as a score ofor =4 on a 7-point Global Overall Symptom (GOS) scale. Patients were excluded if they had predominant symptoms of heartburn or regurgitation; after a normal baseline endoscopy, patients were randomized to esomeprazole 40 mg once daily or placebo for 8 wk. The primary outcome measure was symptom relief (GOSor =2) at 8 wk.Of the 502 enrolled patients, 224 were randomized. The main reasons for exclusion were abnormal endoscopic findings, especially esophagitis. A significantly greater proportion of patients in the esomeprazole group achieved symptom relief at 4 but not at 8 wk compared to placebo: 4 wk esomeprazole 50.5% versus placebo 32.2%, p= 0.009; 8 wk esomeprazole 55.1% versus placebo 46.1%, p= 0.16. A similar relationship at 4 and 8 wk was seen for symptom resolution (GOS = 1) and improvement (DeltaGOSor =2).For the primary outcome measure of symptom relief at 8 wk, there was no statistically significant difference between esomeprazole 40 mg once a day and placebo. However, at 4 wk, esomeprazole was significantly more effective than placebo for symptom relief. The difference in therapeutic gain between 4 and 8 wk was largely due to a higher placebo response rate at 8 wk.

Symptom response at 1-week predicts responders at 4-weeks with esomeprazole (40 mg bid and od) in patients with uninvestigated dyspepsia