A positron emission tomography microdosing study with a potential antiamyloid drug in healthy volunteers and patients with Alzheimer's disease.

This work describes a microdosing study with an investigational, carbon 11-labeled antiamyloid drug, 1,1'-methylene-di-(2-naphthol) (ST1859), and positron emission tomography (PET) in healthy volunteers (n = 3) and patients with Alzheimer's disease (n = 6). The study aimed to assess the distribution and local tissue pharmacokinetics of the study drug in its target organ, the human brain. Before PET studies were performed in humans, the toxicologic characteristics of ST1859 were investigated by an extended single-dose toxicity study according to guidelines of the Food and Drug Administration and European Medicines Agency, which are relevant for clinical trials with a single microdose. After intravenous bolus injection of 341 +/- 21 MBq [(11)C]ST1859 (containing <11.4 nmol of unlabeled ST1859), peripheral metabolism was rapid, with less than 20% of total plasma radioactivity being in the form of unchanged parent drug at 10 minutes after administration. In both the control and patient groups, uptake of radioactivity into the brain was relatively fast (time to reach maximum concentration, 9-17 minutes) and pronounced (maximum concentration [standardized uptake value], 1.3-2.2). In both healthy volunteers and patients, there was a rather uniform distribution of radioactivity in the brain, including both amyloid-beta-rich and -poor regions, with slow washout of radioactivity (half-life, 82-185 minutes). In conclusion, these data provide important information on the blood-brain barrier penetration and metabolism of an investigational antiamyloid drug and suggest that the PET microdosing approach is a useful method to describe the target-organ pharmacokinetics of radiolabeled drugs in humans.

Clinical study of the therapeutic efficacy and safety of emedastine difumarate versus terfenadine in the treatment of seasonal allergic rhinitis.

OBJECTIVE: Emedastine is a new H1-receptor antagonist endowed with potent and selective antihistamine activity. The aim of this study was to evaluate the therapeutic efficacy and tolerability of emedastine difumarate (CAS 87233-62-3) in Caucasian patients in the treatment of seasonal allergic rhinitis as compared to terfenadine (CAS 50679-08-8). METHODS: A total of 130 patients suffering from grass pollen allergic rhinitis were randomly assigned to 14 days treatment with either emedastine difumarate (2 mg b.i.d.) or terfenadine (60 mg b.i.d.) in a double-blind, randomised, crossover design. Primary efficacy parameter was a Total Severity Symptom Score, including among symptoms nasal congestion, sneezing, rhinorrhea, nasal/throat/palate itching, eye itching and lacrimation. Safety was assessed on routine laboratory tests and recording vital signs and adverse events (AEs). RESULTS: Emedastine 2 mg b.i.d. was significantly more effective than terfenadine 60 mg b.i.d. in reducing Total Symptom Severity Score (p = 0.0258). This statistical significant difference was also obtained in controlling sneezing and rhinorrhea (p = 0.003). Moreover, both the physician and patients indicated emedastine as the preferred therapy (p < 0.01). Forty-seven drug related AEs were reported for emedastine (= 51.07 %) and 53 for terfenadine (64.15 %), most of them involving the CNS. CONCLUSION: The results of study show that emedastine difumarate is more effective than terfenadine in the symptomatic management of seasonal allergic rhinitis and is particularly active in controlling the main nasal symptoms, such as sneezing and rhinorrhea; it is safe and well tolerated in this therapeutic indication, while related AEs are less if compared to those displayed by terfenadine.

Clinical study of the therapeutic efficacy and safety of emedastine difumarate versus cetirizine in the treatment of seasonal allergic rhinitis.

OBJECTIVE: The therapeutic efficacy and tolerability of emedastine difumarate (CAS 87233-62-3) in male and female Caucasian patients with seasonal allergic rhinitis as compared to cetirizine (CAS 83881-51-0) was evaluated. METHODS: The study was designed as a double-blind, randomised, parallel groups comparison of two antihistamines administered by oral route (emedastine 4 mg o.d. versus cetirizine 10 mg o.d.) in a population of 120 patients suffering from grass pollen allergic rhinitis. The duration of the treatment period was 14 days. Primary efficacy variable was a total symptoms score (including among symptoms nasal congestion, sneezing, rhinorrhea, nasal/throat/palate itching, eye itching and lacrimation) evaluated after 14 days of treatment vs. baseline value. Safety was assessed on routine laboratory assays and recording vital signs and adverse events (AEs). RESULTS: The between-group difference in primary efficacy variable averaged over the 2-week treatment period was not statistically significant. Results clearly showed that no significant difference exists between the two treatments as far as total symptoms score evaluated after 14 days of treatment vs. baseline values are concerned. Therefore, the efficacy profiles of the study medications are overlapping. The pattern and incidence of AEs was similar in both treatment groups. The most frequent AEs with both compounds were related to the CNS, headache being the most reported one. In particular, this study seems to disclose a slighter tendency to drowsiness with emedastine than with cetirizine. CONCLUSIONS: Both drugs under investigation in this trial appear to be effective for relieving the symptoms of seasonal allergic rhinitis in Caucasian adult patients. The results demonstrate that emedastine 4 mg o.d. is comparable in efficacy to cetirizine 10 mg once daily in the symptomatic management of seasonal allergic rhinitis. Moreover, based on the results of this study, emedastine can be considered a safe and well-tolerated drug and its safety profile seems to resemble that of cetirizine.