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AIMS SD-1077, a selectively deuterated precursor of dopamine (DA) structurally related to L-3,4-dihydroxyphenylalanine (L-DOPA), is under development for treatment of motor symptoms of Parkinson's disease. Preclinical models have shown slower metabolism of central deuterated DA. The present study investigated the peripheral pharmacokinetics (PK), metabolism and safety of SD-1077. METHODS Plasma and urine PK of drug and metabolites and safety after a single oral 150 mg SD-1077 dose were compared to 150 mg L-DOPA, each in combination with 37.5 mg carbidopa (CD) in a double-blind, two-period, crossover study in healthy volunteers (n = 16). RESULTS Geometric least squares mean ratios (GMRs) and 90% confidence intervals (90% CI) of SD-1077 vs. L-DOPA for Cmax , AUC0-t , and AUC0-inf were 88.4 (75.9-103.1), 89.5 (84.1-95.3), and 89.6 (84.2-95.4), respectively. Systemic exposure to DA was significantly higher after SD-1077/CD compared to that after L-DOPA/CD, with GMRs (90% CI) of 1.8 (1.45-2.24; P = 0.0005) and 2.06 (1.68-2.52; P

Background: Spirometric lung age expresses lung function relative to chronological age. It has been effective in encouraging smoking cessation and has been used in the assessment of asthma. Reslizumab, a humanized anti-interleukin-5 monoclonal antibody, is approved as add-on therapy for adults with severe asthma and elevated blood eosinophils. Objective: To assess the effect of reslizumab versus placebo on the change in lung age over 52 weeks and the correlation between change in lung age and quality of life in moderate-to-severe asthma. Methods: This was a post hoc analysis of two randomized, double-blind, placebo-controlled trials. Patients ages 12-75 years with moderate-to-severe, inadequately controlled asthma and elevated blood eosinophils received intravenous reslizumab 3.0 mg/kg or placebo every 4 weeks for 1 year. Spirometry was performed every 4 weeks, and the Asthma Quality of Life Questionnaire (AQLQ) score was assessed at baseline and weeks 16, 32, and 52. Results: Mean improvement in lung-age deficit at week 52 was -8.73 years for reslizumab versus -3.80 years for placebo, a treatment difference of 5 years (p www.clinicaltrials.gov .

SD-1077, a selectively deuterated precursor of dopamine (DA) structurally related to L-3,4-dihydroxyphenylalanine (L-DOPA), is under development for treatment of motor symptoms of Parkinson's disease. Preclinical models have shown slower metabolism of central deuterated DA. The present study investigated the peripheral pharmacokinetics (PK), metabolism and safety of SD-1077.Plasma and urine PK of drug and metabolites and safety after a single oral 150 mg SD-1077 dose were compared to 150 mg L-DOPA, each in combination with 37.5 mg carbidopa (CD) in a double-blind, two-period, crossover study in healthy volunteers (n = 16).Geometric least squares mean ratios (GMRs) and 90% confidence intervals (90% CI) of SD-1077 vs. L-DOPA for CSD-1077/CD demonstrated the potential to prolong exposure to central DA at comparable peripheral PK and safety to the reference L-DOPA/CD combination. A single dose of SD-1077 is safe for further clinical development in Parkinson's disease patients.