081 Lorexys Phase 2a Results: Patient's Global Impression of Change (PGIC)

Objectives: We explored whether the sensitivity of treatment trials for women with sexual dysfunction may have been overly limited by restricting answer sets to the usual multiple-choice (M-C)approach. One such M-C scale is the Patient’s Global Impression of Change (PGIC). Previous trials have tended to show with active treatment a modal response on the PGIC at “minimally improved,” but the next higher level of improvement scaled was “much improved.” Psychometric analysis favored interpolating “moderately improved” between these answers. Also, in such an early trial, in which the size of the database is modest and the interpretation of Results is most open to question, the sensitivity issue was explored by asking subjects for their personal interpretation of results. Materials and Methods: Thirty basically healthy premenopausal women with HSDD were to be treated in a one-way crossover with four-week treatment periods of bupropion SR, then low-dose Lorexys (combination of low doses of bupropion and trazodone), then moderate-dose Lorexys (combination of moderate doses of bupropion and trazodone), with a washout of 1-4 weeks between treatments. Change in severity was measured with Female Sexual Function Index – Desire subscale (FSFI-D), Female Sexual Distress Scale – Revised (FSDS-R), Item 13 on low sexual desire, and a Patient’s Global Impression of Change modified to include a moderate improvement category and a free-text response to “Please tell us what you mean by this answer in a few words.” Results Moderate dose Lorexys was associated with 58% of subjects improving at least moderately; bupropion, with 24% so responding (p<0.05 on Fisher’s exact test, 2-tailed). The modal response to Lorexys moderate dose was “moderately improved,” that to bupropion alone was “minimally improved.” Most of the free-text responses gave new qualitative information; the majority enhanced interpretation of the patient’s change with treatment. Of the common adverse events associated with extended-release trazodone in the Phase III Major Depressive Disorder (MDD)registration trial, all but dry mouth appear to have been attenuated by adding bupropion in the Lorexys study. Conclusions: The modified scaling of the Patient’s Global Impression of Change allowed greater delineation of responses to treatment. The free-text responses confirmed and expanded upon the multiple-choice Results, giving the interpretability of results greater depth. Disclosure: Work supported by industry: no.