Pharmacokinetics and Safety of a 1:1 Mixture of Doxecitine and Doxribtimine: Open-label Phase 1 Single Ascending Dose and Food Effect Studies in Healthy Adults.

Purpose: Doxecitine (deoxycytidine [dC]) and doxribtimine (deoxythymidine [dT]) powder for oral solution is a 1:1 mixture consisting of equal weights 2'-deoxycytidine (dC) and 2'-deoxythymidine (dT). Doxecitine and doxribtimine (referred to as study drug) is being developed as treatment for people with thymidine kinase 2 deficiency (TK2d). TK2d is an ultra-rare mitochondrial DNA depletion and multiple deletion syndrome characterized by progressive muscle weakness and premature death.

Prevalence of Hepatic Encephalopathy from a Commercial Medical Claims Database in the United States.

Introduction: Hepatic encephalopathy (HE), a complication of cirrhosis, is associated with increased healthcare resource utilization and mortality, and impaired quality of life. Information on the prevalence of HE in the US general population is limited.

Methods: Prevalence of HE was estimated by sequential stepwise data analysis of the Symphony Health anonymized patient-level data (APLD) claims database.

Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: The MIRROR study.

Objective: To assess dose-response effects of the anti-CD20 monoclonal antibody ofatumumab on efficacy and safety outcomes in a phase 2b double-blind study of relapsing forms of multiple sclerosis (RMS).

Methods: Patients (n = 232) were randomized to ofatumumab 3, 30, or 60 mg every 12 weeks, ofatumumab 60 mg every 4 weeks, or placebo for a 24-week treatment period, with a primary endpoint of cumulative number of new gadolinium-enhancing lesions (per brain MRI) at week 12. Relapses and safety/tolerability were assessed, and CD19+ peripheral blood B-lymphocyte counts measured.

A randomized, fixed-dose, dose-response study of ropinirole prolonged release in advanced Parkinson's disease.

Aim: This Phase IV, double-blind, randomized, parallel-group study characterized the dose-response and tolerability of fixed doses of ropinirole prolonged release (PR) in subjects with advanced Parkinson's disease.

Patients & Methods: Subjects receiving concomitant l-dopa received once-daily ropinirole PR 4, 8, 12, 16 or 24 mg, or placebo, up-titrated for 13 weeks, maintained for 4 weeks.

Results: At maintenance period week 4, ropinirole PR significantly reduced total awake 'Off-time' (16 mg; p = 0.

A fixed-dose, dose-response study of ropinirole prolonged release in early stage Parkinson's disease.

Aim: This Phase IV, double-blind, randomized, parallel-group study characterized the dose-response and tolerability of fixed doses of ropinirole prolonged release (PR).

Patients & Methods: Subjects with early Parkinson's disease (PD) received placebo or ropinirole PR 2, 4, 8, 12 or 24 mg once daily, up-titrated to randomized or highest tolerated dose, maintained for 4 weeks.

Results: The primary end point was not met (change from baseline in Unified PD Rating Scale motor score).

Challenges and opportunities in designing clinical trials for neuromyelitis optica.

Current management of neuromyelitis optica (NMO) is noncurative and only partially effective. Immunosuppressive or immunomodulatory agents are the mainstays of maintenance treatment. Safer, better-tolerated, and proven effective treatments are needed.

Long-term, open-label, safety study of once-daily ropinirole extended/prolonged release in early and advanced Parkinson's disease.

Long-term safety of once-daily ropinirole extended/prolonged release (ropinirole XL/PR) was evaluated in subjects with early and advanced Parkinson's disease (PD) in this study, 101468/248. Subjects (n = 419) who completed one of three prior studies evaluating ropinirole XL/PR for the treatment of PD were enrolled in this open-label, multicenter, extension study, and were to be followed for up to 73 months. Ropinirole XL/PR was titrated/continued, and adjusted as appropriate during the maintenance phase (maximum 24 mg/d).

Dose response of Gabapentin Enacarbil versus placebo in subjects with moderate-to-severe primary restless legs syndrome: an integrated analysis of three 12-week studies.

Background: The efficacy and tolerability of gabapentin enacarbil (Horizant®; GlaxoSmithKline, Brentford, UK) has been demonstrated in several restless legs syndrome (RLS) phase II and phase III clinical studies at various doses from 600 mg to 2400 mg.

Objective: The objective of this study was to evaluate key efficacy and safety outcomes in subjects with RLS treated with once-daily gabapentin enacarbil 600 mg, 1200 mg, 1800 mg and 2400 mg, providing supportive evidence of the efficacy of gabapentin enacarbil 600 mg compared with higher doses and placebo.

Study Design: Integrated post hoc analysis of three 12-week, randomized, double-blind, placebo-controlled trials in subjects with RLS.

Extended-release bupropion for patients with major depressive disorder presenting with symptoms of reduced energy, pleasure, and interest: findings from a randomized, double-blind, placebo-controlled study.

Objective: This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of extended-release bupropion (bupropion XL) in the treatment of major depressive disorder (MDD) with prominent symptoms of decreased energy, pleasure, and interest.

Method: Eligible adult outpatients meeting DSM-IV criteria for MDD were randomly assigned to bupropion XL 300 to 450 mg/day (N = 135) or placebo (N = 139) for 8 weeks. The primary efficacy measure, change from baseline on the 30-item Inventory of Depressive Symptomatology-Self Report (IDS-IVR-30) total score, was obtained using interactive voice response (IVR) technology.

Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials.

Background: Although it is widely believed that the various classes of antidepressants are equally effective, clinically meaningful differences may be obscured in individual studies because of a lack of statistical power. The present report describes a meta-analysis of original data from a complete set of studies comparing the norepinephrine/dopamine reuptake inhibitor (NDRI) bupropion with selective serotonin reuptake inhibitors (SSRIs; sertraline, fluoxetine, or paroxetine).

Method: Individual patient data were pooled from a complete set of 7 randomized, double-blind studies comparing bupropion (N = 732) with SSRIs (fluoxetine, N = 339; sertraline, N = 343; paroxetine, N = 49) in outpatients with major depressive disorder (DSM-III-R or DSM-IV); 4 studies included placebo (N = 512).