Placebo comparative

Anistreplase has a considerably longer a half-life than streptokinase, ie, 90 min compared to 20 min (87,88). Moreover, it does not require prolonged infusion to achieve its thrombolytic effects. Anistreplase was found to be highly effective after a single intravenous dose of 30 units over a 5-min period compared to a 60-min infusion of 1.5 million units of streptokinase (89—94). In direct comparative studies, anistreplase was as effective as intracoronary (95,96) and intravenously (96—100) adrninistered streptokinase. In a randomized, double-blind, placebo-controUed study (AIMS trial) with 1004 patients given this modified enzyme, the 30-day mortaUty rate was 12.2% for patients receiving placebo, compared to 6.4% for patients who received 30 units of anistreplase intravenously within six hours of the onset of symptoms (101). 

The European Stroke Prevention Study 2 (ESPS-2) trial examined four treatment arms—extended-release dipyridamole (ER-DP) 200 mg twice daily alone, aspirin 25 mg twice daily alone, ER-DP 200 mg twice daily + aspirin 25 mg twice daily, or placebo. In comparison with placebo the overall reduction in stroke risk was 16% with ER-DP alone and 18% with aspirin alone. The combination of ER-DP and aspirin led to a 37% reduction in stroke risk compared to placebo. Compared with aspirin alone, the combination of ER-DP with aspirin reduced the risk of stroke by 23%. 

Part II Composition, Method of Preparation, Controls of Starting Materials, Control Tests on Intermediate Products, Control Tests on the Finished Product, Stability and Other Information (Placebos, Comparator Products, Adventitious Agents, etc.)... 

There is no suitable placebo available or it is impracticable to attempt a true placebo comparator group, for example, in a trial comparing an intravenous with an oral formulation. 

Testosterone gel is effective transdermally, although a report on its use in the form of AA2500 (brand name), which releases 50 or 100 mg/day, points to an unusually high incidence of local sensitivity reactions it is not clear whether this is due to testosterone itself or to excipients absent from the placebo comparator (61). 

In 186 patients randomized equally to amiodarone 200 mg/day, sotalol 160-480 mg/day, or placebo, the incidence of atrial fibrillation after 6 months was higher in those taking placebo compared with amiodarone and sotalol and higher in those taking sotalol compared with amiodarone (19). Of the 65 patients who took amiodarone, 15 had significant adverse effects after an average of... 

Burtness B, Goldwasser MA et al. (2005) Phase 111 randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer an Eastern Cooperative Oncology Group study. J Clin Oncol 23(34) 8646-8654... 

Skin In a 26-week randomized placebo-controlled study in 527 patients, mean age 55 years, with type 2 diabetes taking metformin, alogliptin 12.5 or 25 mg/day was associated with skin-related adverse events in 7.7% of those taking placebo compared with 12% in both alogliptin groups. Dry skin, pruritus, rashes, and eczema were reported one patient stopped taking alogliptin because of an eruption [48. ... 

Cardiovascular Several cardiovascular adverse associated with roflmnilast were recently analyzed using a metaanalysis comparing the overall incidence of serious adverse events in 12,054 COPD patients [91 ]. The frequency of atrial fibrillation was fotmd to be 0.4% among patients receiving roflumilast compared to 0.2% in the placebo group (p = 0.02). Interestingly, myocardial infarction and chest pain were reported more frequently with placebo compared to those that received roflumilast. However, no statistically significant difference was foxmd between placebo and roflumilast. 

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