Mais les résultats doivent être attendus longtemps et il n'y a généralement pas de temps doxycycline prix L'autre cas, c'est que l'achat d'un ou d'un autre antibiotique dans une pharmacie classique nécessite des dépenses matérielles considérables et pas toutes les personnes ne peuvent acheter des produits pharmaceutiques aussi coûteux.

[poster title]

EVP-6124 - Safety, Tolerability and Cognitive Effects of a Novel α7 Nicotinic Receptor Agonist in
Alzheimer’s Disease Patients on Stable Donepezil or Rivastigmine Therapy
Dana Hilt,1 Beth Safirstein,2 David Hassman,3 Jeffrey Apter,4 Stephen Thein,5 Paul Maruff,6 John Harrison,6 Maria Gawryl,1 Gerhard Koenig,1
1EnVivo Pharmaceuticals, Watertown, MA, 2MD Clinical, Hallandale Beach FL, 3Comprehensive Clinical Research, Berlin, NJ, 4Global Medical Institutes, Princeton, NJ, 5Pacific Research Network, Inc. San Diego, CA, 6CogState Ltd, Melbourne, Australia ABSTRACT
Adverse Events per Body System
Approved symptomatic therapies for Alzheimer’s disease (AD) provide modest relief. In the future, it is likely that symptomatic treatments will be utilized with AD modifying • Randomised, double-blind, placebo-controlled, ascending CogState/NTB Outcome Measures
therapies, the development of which are currently a primary focus of research. The dose in patients with mild to modera te probable Alzheimer's nicotinic a-7 receptor agonist may be an attractive drug candidate to potentially improve cognition in Alzheimer’s disease patients either as a stand-alone therapy or • 3 days observation, 1 month active or placebo dosing (5 days in combination with other symptomatic treatments. under observation/in-patient and 23 days outpatient) EVP-6124 is a novel, potent, and selective alpha7 nicotinic receptor agonist. EVP-6124 has an excellent brain to plasma exposure ratio and has shown excellent efficacy and potency in a number of animal models of cognition. Four clinical studies • 0.1, 0.3, or 1.0 mg of EVP-6124, placebo in >125 healthy normal human subjects have been completed with EVP-6124, • AD patients stabilized on AChEI (donepezil or rivastigmine) including a single-ascending-dose study, a 14-day multiple-ascending-dose study, a 21-day, multiple-dose study, and a single-dose relative bioavailability, food and gender effect study. EVP-6124 exhibited linear kinetics over the range of 1 to 180 mg Primary endpoints
and demonstrated a half-life suitable for once daily dosing. EVP-6124 appears to be safe and well-tolerated for up to 21 days as measured by adverse events, vital signs, • Safety, clinical safety and laboratory assessments continuous cardiac monitoring, physical examination, and clinical evaluations. In addition, in normal volunteers, EVP-6124 demonstrated pro-cognitive Secondary endpoints
effects (CogState testing) in various cognitive domains including executive function. • PK of EVP-6124 and AChE Inhibitors for potential drug-drug The safety and efficacy of EVP-6124 was assessed in a Phase 1b study of 48 mild to moderate AD patients 60-80 years of age, on stable donepezil or rivastigmine therapy. Patients were dosed with placebo or two different doses of EVP-6124 (0.3 or 1.0 mg/d) for 28 days. Safety was evaluated by adverse events, ECG, and clinical Tertiary endpoints
laboratory measures. Cognitive effects were measured by CogState computerized Effect Size of 1 mg Dose In Pilot AD Study
cognitive testing and a subset of NTB scales. • Cognition testing (CogState and subset of NTB scales) EVP-6124 appeared to be safe and well tolerated with no significant adverse events CogState
reported more frequently in treated versus placebo patients; there were no SAEs Effect Size
Inclusion Criteria
reported. Subjects exposed to EVP-6124 in addition to donepezil or rivastigmine EVP-6124 SUMMARY
showed an increase in cognitive function, primarily in the domains of non-verbal learning, memory, and executive function.
• Probable AD consistent with NINCDS and ADRDA criteria These data suggest that EVP-6124 administered to AD subjects on stable • MRI or computed tomography (CT) scan within 24 months • EVP-6124 safe and well tolerated (up to 28 days) in AD cholinesterase inhibitor therapies, may have potential benefit and that further study in this patient population is indicated. Larger phase II studies are currently being • Pro-cognitive effects in addition to AChEI were observed initiated in both Alzheimer’s disease and schizophrenia. • Modified Hachinski Ischemic Score ≤ 4 – Effects appear to increase over the treatment period • Patient living in setting not requiring continuous nursing care – Effects are dose dependent for several cognition measurements • Patient on stable dose of AChEI (donepezil or rivastigmine) • EVP-6124 has normalizing effects on a number of evoked for at least 4 months prior to study initiation response biomarkers in schizophrenic patients on long term • If prior treatment with either memantine or galantamine, INTRODUCTION
neither medication within 28 days of baseline Nicotinic Alpha-7 Receptor: Va
lidated Target for Cognition
Main Exclusion
• Hospitalization within 4 weeks before or during screening Days on Treatment
• Multiple selective agonists (AR-R-17779, EVP-6124, SSR180711, MEM3454, A-582941 improve memory in • Participation in another clinical trial within 3 months • EVP-6124 may have pro-cognitive and clinical benefits when • Memory’s/Roche MEM3454 has shown promising phase IIa Cognition Dose-Response Analysis
added to long term AChEI therapy in mild/moderate AD • Insufficiently controlled diabetes mellitus A number of cognition measurements demonstrated statistically • Warrants further studies to define the magnitude of pro- • Amyloid peptide Ab42 peptide interacts with a7 receptor cognitive effects and potential clinical benefits in both AD and • Major depression within the last five years • Multiple data suggesting potential impact on disease • Geriatric Depression Scale score > 5 • Stroke within six months before screening, or concomitant • Specific degenerative CNS disease diagnosis other than Alzheimer’s disease (e.g., Huntington’s disease, Jacob-


Qcm - richard 2010-1

Rayons X et gamma et rayonnements particulaires 2010-11 Question 9 Rayons X et gamma et rayonnements particulaires Cochez la (ou les) proposition(s) vraie(s) A- Les protons et les neutrons sont les particules fondamentales constituant le noyau atomique. B- Deux isotopes d’un élément se différencient par leur nombre de neutrons. C- Cobalt-60 (Z = 27) et le nickel-60

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