[Effectiveness and safety of safinamide as add-on to levodopa in patients with parkinson's disease: non-interventional study]. / Wirksamkeit und Sicherheit von Safinamid als Zusatztherapie zu Levodopa bei Parkinson-Patienten: eine nicht-interventionelle Beobachtungsstudie.

AIM: Safinamide (Xadago®) is a newly approved selective MAO-B inhibitor for the treatment of Parkinson's Disease (PD). The X-TRA study investigated the efficacy and tolerability of the substance under clinical practice conditions. METHODS: Prospective, observational study in unselected patients in line with safinamide product specifications. RESULTS: Of the 299 patients included (65.9 % males, age 72.7 ± 9.0 years, duration of disease 7.8 ± 5.9 years), at the beginning of the documentation 229 patients (81.2 %) received L-dopa, 108 (39.3 %) combination drugs containing L-dopa, 172 (59.3 %) a dopamine agonist and 23 (8.3 %) a COMT inhibitor. Of these, 203 patients were followed-up over a period of 6 months. The MDS-UPDRS Part III score for motor symptoms decreased from a baseline value of 48.2 ± 22.1 points by 6.8 ± 14.5 points at the end of the study. The Non-Motor Symptoms Scale score indicating the presence or absence of motor symptoms decreased from a baseline value of 57.6 ± 42.1 by 9.3 ± 2.1 points, the Abnormal Involuntary Movement Score from 4.6 ± 5.8 points by 0.9 ± 2.7 points.The Parkinson's Disease Score (PDQ-8) for assessing quality of life decreased from a baseline value of 39.4 ± 18.2 points by 4.3 ± 13.7 points, reflecting an improvement. In total, 300 adverse events were classified as related to safinamide in 132 patients (44.1 %). Fifty-three events were serious (in 15 patients; 5 %). Seventy-four patients (24.7 %) discontinued safinamide therapy because of adverse drug reactions. CONCLUSIONS: Safinamide therapy improved the motor and non-motor symptoms as well as the quality of life in PD. Most patients tolerated the therapy well. The only side effects that occurred are those described in the patient information leaflet.

One-year immunogenicity kinetics and safety of a purified chick embryo cell rabies vaccine and an inactivated Vero cell-derived Japanese encephalitis vaccine administered concomitantly according to a new, 1-week, accelerated primary series.

BACKGROUND: Conventional rabies pre-exposure prophylaxis (PrEP) and Japanese encephalitis (JE) primary series vaccination regimens each require up to 4 weeks to complete and, thus, may not be feasible for individuals who need these immunizations on short notice. This Phase 3b, randomized, controlled, observer-blind study evaluated the immunogenicity and safety of concomitant administration of a purified chick embryo cell culture rabies vaccine and an inactivated, adsorbed JE vaccine according to an accelerated (1 week) regimen when compared with the conventional regimens (4 weeks). This report describes the kinetics of immune responses up to 1 year after vaccination. METHODS: A total of 661 healthy adults (18 to ≤65 years) were randomized into the following accelerated or conventional vaccine regimens: Rabies + JE-Conventional, Rabies + JE-Accelerated, Rabies-Conventional and JE-Conventional. Immunogenicity was assessed by virus neutralization tests. Safety and tolerability were also evaluated. RESULTS: Irrespective of rabies vaccination regimen, ≥97% of subjects had adequate levels of rabies virus neutralizing antibody (RVNA) concentrations (≥0.5 IU/ml) up to Day 57, with percentages of subjects with RVNA concentrations ≥0.5 IU/ml at Day 366 ranging between 68% in the Rabies + JE-Accelerated group and 80% of subjects in the Rabies-Conventional group. The Rabies + JE-Accelerated group revealed high JE neutralizing antibody titers at all-time points. At Day 366, the percentage of subjects with antibody titers indicative of seroprotection (PRNT50 titers ≥1:10) remained high across JE vaccine groups (86-94%). CONCLUSIONS: The accelerated PrEP rabies and JE vaccination regimens, once licensed, could represent a valid alternative in the short-term to currently recommended conventional regimens. The concomitant administration of these two vaccines does not compromise immune responses to any of the vaccine antigens particularly when aiming for short-term protection. Further evidence will clarify the need for and timing to administration of rabies vaccine booster doses in subjects primed with an accelerated PrEP regimen. (NCT01662440).

Evaluation of rabies immunogenicity and tolerability following a purified chick embryo cell rabies vaccine administered concomitantly with a Japanese encephalitis vaccine.

BACKGROUND: For individuals traveling at short notice to rabies and Japanese encephalitis (JE) endemic countries, concomitant administration of travel vaccines within a short period is often required. METHODS: The aim of this study was to determine whether an accelerated (one-week: Days 1-8) pre-exposure rabies (Rabipur(®), Novartis Vaccines) vaccination regimen administered concomitantly with a Japanese encephalitis (JE) vaccination (Ixiaro(®), Valneva) regimen, is non-inferior to the standard (four-week: Days 1, 8, 29) rabies regimen administered alone or concomitantly with the JE vaccine. Healthy adults (18 to ≤ 65 years) were randomized into Rabies + JE-Standard, Rabies + JE-Accelerated, Rabies-Standard and JE-Standard groups. Relative immunogenicity for rabies in each regimen was assessed using the rapid fluorescent focus inhibition test. Safety was evaluated up to and including Day 57. RESULTS: Non-inferior immunogenicity for rabies was established between the Rabies + JE-Accelerated group compared to both the Rabies-Standard and Rabies + JE-Standard groups; as well as between the Rabies + JE-Standard regimen and the Rabies-Standard regimen. By Day 57, adequate neutralizing levels were achieved by 97-100% of subjects across all groups. Adverse events (AEs) were comparable for all groups. CONCLUSIONS: An accelerated pre-exposure rabies and JE vaccination regimen is non-inferior to the standard four-week rabies regimen and may thus provide a more convenient regimen for individuals traveling to endemic countries at short notice. NCT01662440.

Short-Term Immunogenicity and Safety of an Accelerated Pre-Exposure Prophylaxis Regimen With Japanese Encephalitis Vaccine in Combination With a Rabies Vaccine: A Phase III, Multicenter, Observer-Blind Study.

BACKGROUND: The current Japanese encephalitis (JE) vaccination regimen requires two doses and 4 weeks to complete, which may not always be feasible for travelers on short notice. One of the primary endpoints of this phase III study was to demonstrate noninferiority of immune responses to a JE vaccine following an accelerated 1-week JE vaccination regimen administered concomitantly with a rabies vaccine as compared to a standard 4-week JE regimen alone. In addition, the immunogenicity of concomitant administration of JE and rabies vaccines following standard regimens was evaluated, as well as the tolerability and safety profile of each regimen under study. METHODS: Healthy adults aged 18 to ≤65 years were randomized to regimens with an accelerated or standard schedule: JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n = 56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction neutralization test (PRNT50 ) titer of ≥1 : 10, measured 28 days after last active vaccine (LAV) administration. Solicited reactions were collected 7 days after each vaccination; spontaneously reported adverse events (AEs) and serious AEs were monitored up to day 57. This paper reports results until day 57. RESULTS: Noninferiority of immune responses was established for JE+rabies-accelerated compared to the JE-standard regimen 28 days after LAV administration. Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard groups, respectively, achieved PRNT50 titers of ≥1 : 10 at 28 days after LAV administration. No impact of concomitant rabies vaccination was observed either on immune responses or on the safety profile of the JE vaccine. CONCLUSIONS: This was the first randomized, controlled trial that demonstrated the strong short-term immunogenicity of a new, accelerated, 1-week JE-regimen, which was noninferior to that of the standard regimen, with a satisfactory tolerability and safety profile and no impact of concomitant rabies vaccination. This accelerated regimen, if licensed, could potentially be a valid alternative for individuals requiring a primary series of JE vaccination and rabies pre-exposure prophylaxis on short notice.

Clinical trial to evaluate the safety and immunogenicity of a trivalent surface antigen seasonal influenza vaccine produced in mammalian cell culture and administered to young and elderly adults with and without A(H1N1) pre-vaccination.

UNLABELLED: Vaccination against influenza is an important means of reducing morbidity and mortality in subjects at risk. The prevalent viral strains responsible for seasonal epidemics usually change annually, but the WHO recommendations for the 2011/2012-season in the Northern hemisphere included the same antigens as for the previous season. We conducted a single-center, single-arm study involving 62 younger (18-60 years) and 64 older (>60 years) adults to test the immunogenicity, safety and tolerability of a trivalent surface antigen, inactivated influenza vaccine produced in mammalian cell-culture. The vaccine contained 15 µg hemagglutinin of each of the virus strains recommended for the 2011-2012 Northern hemisphere winter season (A/California/7/09 (H1N1)-; A/Perth/16/09 (H3N2)-; B/Brisbane/60/08-like strain) in a non-adjuvanted preservative-free formulation. Antibody response was measured by hemagglutination inhibition 21 days after immunization. Adverse events and safety were assessed using subject diary cards and telephone interviews. Seroconversion or a 4-fold antibody increase in antibody titers was detectable against A(H1N1) in 68% of both younger and older adults, against A(H3N2) in 53% and 27%, and against the B influenza strain in 35% and 17%. Antibody titers of 40 or more were observed against A(H1N1) in 87% and 90% of younger and older adults, against A(H3N2) in 98% and 98%, and against the B influenza strain in 93% and 90%. Pre-vaccination antibody titers were protective against A(H1N1), A(H3N2) and B in 38%, 58% and 58%, respectively, of younger and in 43%, 88% and 70% of older adults. Among subjects with previous A(H1N1) vaccination only 48% of younger and 47% of older adults had protective A(H1N1) antibodies at inclusion. Adverse reactions were generally mild. The most frequently reported reactions were pain at the injection site, myalgia and fatigue. The vaccine generated protective antibodies against all three viral strains and had an acceptable safety profile in both younger and older adults. TRIAL REGISTRATION: ClinicalTrials.govNCT01422512.

Phase I comparability of recombinant human albumin and human serum albumin.

Recombinant human albumin (rHA) is a highly purified animal-, virus-, and prion-free product developed as an alternative to human serum albumin (HSA), to which it is structurally equivalent. The present investigation compared the safety, tolerability, and pharmacokinetics/pharmacodynamics of rHA with HSA. Two double-blind, randomized trials were performed in healthy volunteers using intramuscular (IM) and intravenous (IV) administration. The IM trial included 500 volunteers, each receiving 5 repeat doses of 5 mg (100 subjects), 15 mg (100 subjects), or 65 mg (300 subjects) of rHA or HSA. Thirty volunteers participated in the IV trial, each receiving ascending doses (10 g, 20 g, and 50 g) of either rHA or HSA. In both trials, all adverse events were recorded and conventionally classified; potential allergic responses were also monitored. Blood samples were taken in both studies to test for IgG or IgE antibodies against test products and potential impurities. For the IV study, pharmacokinetic/pharmacodynamic assessments were performed, including measurement of serum albumin, colloid osmotic pressure, and hematocrit pre- and postinfusion. Nine subjects in the IM study (4 recipients of rHA and 5 of HSA) reported drug-related, potentially allergic events; all but 2 of these were skin related. No serious or potentially allergic events were reported with either product in the IV study. There was no immunological response to either product, and dose level did not influence the study outcomes. Serum albumin, colloid osmotic pressure changes, and hematocrit ratio were as expected, with no differences between rHA and HSA. rHA and HSA exhibited similar safety, tolerability, and pharmacokinetic/pharmacodynamic profiles, with no evidence of any immunological response.