Trial 1 was a randomized, placebo-controlled, double-blind, parallel-group study of 98 adult patients with a median age of 36 years. Patients who had developed moderate to severe cutaneous or abdominal or mild to moderate laryngeal attacks of HAE were randomized to receive either Firazyr 30 mg or placebo by subcutaneous injection. Patients with severe laryngeal attacks of HAE received open-label Firazyr 30 mg. The primary endpoint was assessed using a 3-item composite visual analog score (VAS), comprised of averaged assessments of skin swelling, skin pain, and abdominal pain. Response was defined as at least a 50% reduction from the pretreatment composite 3-item VAS score (Figure 2). The median time to 50% reduction in symptoms for patients with cutaneous or abdominal attacks treated with Firazyr (n=43) compared to placebo (n=45) was hours [95% CI , ] versus hours [95% CI , ], respectively (p<).
Ute’s struggles were of a different nature, as she developed bulimia in response to the weight gain induced by her dosing of Oral-Turinabol. The psychological trauma would later manifest itself in depression, too. “The bulimia lasted until 2002, but the depression comes back in waves,” she says. “This is why I am essentially a pensioner now.” Andreas, reaching across to pat her knee, interjects. “It’s not that bad,” he says, with an indulgent laugh. “We keep each other up. What else are you married for?” The two of them, for all the anguish they have endured, share an endearing streak of black humour.
Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including Candida albicans . Experimentally, resistance usually arises as a result of mutations in the sterol biosynthesis pathway. Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step. Multidrug-resistance (MDR) genes can also play a role in reducing cellular levels of the drug. As azole antifungals all act at the same point in the sterol pathway, resistant isolates are normally cross-resistant to all members of the azole family.