Safety and Tolerability of Active Immunotherapy Targeting α-Synuclein with PD03A in Patients with Early Parkinson's Disease: A Randomized, Placebo-Controlled, Phase 1 Study.

BACKGROUND: Immunotherapies targeting α-synuclein aim to limit its extracellular spread in the brain and prevent progression of pathology in Parkinson's disease (PD). PD03A is a specific active immunotherapy (SAIT) involving immunization with a short peptide formulation. OBJECTIVE: This phase 1 study characterized the safety and tolerability of PD03A in patients with early PD. A key secondary objective was to evaluate immunological activity following immunization. METHODS: This was a phase 1 study of two different doses of PD03A versus placebo in PD patients. Patients were randomized (1:1:1) to receive four priming plus one booster vaccination of PD03A 15µg, PD03A 75µg or placebo and were followed for 52 weeks. RESULTS: Overall, 36 patients were randomized, of which 35 received five immunizations and completed the study. All patients experienced at least one adverse event. Transient local injection site reactions affected all but two patients; otherwise most AEs were considered unrelated to study treatment. A substantial IgG antibody response against PD03 was observed with a maximum titer achieved at Week-12. Differences in titers between both active groups versus placebo were statistically significant from the second immunization at Week-8 until Week-52. CONCLUSION: The safety profile and positive antibody response of PD03A supports the further development of active immunotherapeutic approaches for the treatment of PD.

Efficacy and tolerability of escitalopram in 12- and 24-week treatment of social anxiety disorder: randomised, double-blind, placebo-controlled, fixed-dose study.

Selective serotonin reuptake inhibitors are the pharmacological treatment of choice for the treatment of social anxiety disorder (SAD). The efficacy and tolerability of fixed doses of escitalopram were compared to those of placebo in the long-term treatment of generalised SAD, using paroxetine as an active reference. Patients with a DSM-IV diagnosis of SAD between 18-65 years of age were randomised to 24 weeks of double-blind treatment with placebo (n = 166), 5 mg escitalopram (n = 167), 10 mg escitalopram (n = 167), 20 mg escitalopram (n = 170), or 20 mg paroxetine (n = 169). Based on the primary efficacy parameter, Liebowitz Social Anxiety Scale (LSAS) total score at Week 12 (LOCF), a significantly superior therapeutic effect compared to placebo was seen for 5 and 20 mg escitalopram and for all doses for the OC analyses. Further improvement in LSAS scores was seen at Week 24 (OC and LOCF), with significant superiority over placebo for all doses of escitalopram, and 20 mg escitalopram was significantly superior to 20 mg paroxetine. Response to treatment (assessed by a Clinical Global Impression-Improvement score < or = 2) was significantly higher for all active treatments than for placebo at Week 12. Clinical relevance was supported by a significant decrease in all the Sheehan disability scores, and the good tolerability of escitalopram treatment. It is concluded that doses of 5-20 mg escitalopram are effective and well tolerated in the short- and long-term treatment of generalised SAD.