Open-label extension study of flibanserin in women with hypoactive sexual desire disorder.

INTRODUCTION: Hypoactive Sexual Desire Disorder (HSDD) is a common form of Female Sexual Dysfunction characterized by low sexual desire that causes distress or interpersonal difficulty. AIM: This 52-week open-label extension study aimed to assess the safety and tolerability of flibanserin, a postsynaptic 5-HT(1A) agonist/5-HT(2A) antagonist, in women with HSDD. METHODS: Women with HSDD who had completed a trial of flibanserin or flibanserin placebo received flexible-dose flibanserin (50 or 100 mg once daily at bedtime [qhs] or 25 or 50 mg twice daily [bid]) for 52 weeks. MAIN OUTCOME MEASURES: Primary end points were: proportions of women with somnolence, sedation, fatigue, dizziness, nausea, and vomiting (adverse events [AEs] known to be associated with flibanserin); discontinuations due to AEs; and serious AEs. Secondary end points included change from baseline in Female Sexual Distress Scale-Revised total and Item 13 scores and Female Sexual Function Index (FSFI) total and desire domain score scores. FSFI total scores were used to classify women into FSFI remitters (FSFI score >26.55, indicating no clinical sexual dysfunction) and FSFI non-remitters (FSFI score <26.55). RESULTS: Of the 1723 women who received flibanserin, 962 (55.8%) completed 12 months' treatment, and 883 women were exposed to flibanserin 100 mg qhs for ≥180 days. Somnolence, sedation, fatigue, dizziness, nausea, and vomiting were reported by 15.8, 1.6, 7.6, 6.9, 6.3, and 1.4% of participants, respectively. A total of 185 participants (10.7%) discontinued due to AEs. Serious AEs were reported by 1.2% of participants. At study end, 42% of baseline non-remitters had improved their FSFI score to remission level. The proportion of baseline FSFI remitters in remission rose from 83% at week 4 to a stable value of ∼90%. CONCLUSION: Flibanserin was well tolerated. Sexual function improved in women who were not FSFI remitters at baseline, and was maintained in those who were remitters at baseline.

Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine.

BACKGROUND: Calcitonin gene-related peptide (CGRP) may have a causative role in migraine. We therefore hypothesized that a CGRP-receptor antagonist might be effective in the treatment of migraine attacks. METHODS: In an international, multicenter, double-blind, randomized clinical trial of BIBN 4096 BS, a highly specific and potent nonpeptide CGRP-receptor antagonist, 126 patients with migraine received one of the following: placebo or 0.25, 0.5, 1, 2.5, 5, or 10 mg of BIBN 4096 BS intravenously over a period of 10 minutes. A group-sequential adaptive treatment-assignment design was used to minimize the number of patients exposed. RESULTS: The 2.5-mg dose was selected, with a response rate of 66 percent, as compared with 27 percent for placebo (P=0.001). The BIBN 4096 BS group as a whole had a response rate of 60 percent. Significant superiority over placebo was also observed with respect to most secondary end points: the pain-free rate at 2 hours; the rate of sustained response over a period of 24 hours; the rate of recurrence of headache; improvement in nausea, photophobia, phonophobia, and functional capacity; and the time to meaningful relief. An effect was apparent after 30 minutes and increased over the next few hours. The overall rate of adverse events was 25 percent after the 2.5-mg dose of the drug and 20 percent for the BIBN 4096 BS group as a whole, as compared with 12 percent for placebo. The most frequent side effect was paresthesia. There were no serious adverse events. CONCLUSIONS: The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine.