OII‐A‐2

BACKGROUND Based on the results of the Phase 2 trials in insomnia patients, one out of 2 compounds was to be selected for further development. A CUI was developed based on data from Compound 1. The CUI is an integrated measure of clinical benefit/risk over the dose‐range and was proposed as a tool to compare compounds. METHODS The attributes of an ideal agent were identified and included 5 measures of efficacy (e.g. sleep onset, maintenance, quality, sleep stages) and 2 measures of carryover (morning) sedation. These attributes were ranked as a percentage for their relative importance based on market research. Dose‐response analyses were conducted on each endpoint and each scale was normalized based on clinically meaningful differences. CUI was calculated over the dose‐range. Sensitivity analyses were conducted to test for clinically meaningful changes in CUI. Bootstrap parameters of the dose‐response curves were used to build confidence intervals. RESULTS The shape of the CUI‐dose relationship was different for Compound 1 and 2. Peak CUI (80% CI) was 0.345 (0.25–0.43) and 0.436 (0.35–0.52), respectively. Although CUI was greater for Compound 2, peak CUI was observed at doses that were not considered viable. CONCLUSIONS A CUI was used as a novel approach for decision making. CUI is helpful to characterize optimal dose range and is particularly useful when decisions are based on trade‐offs amongst multiple clinical endpoints. Development of Compound 2 was discontinued based on these results. Clinical Pharmacology & Therapeutics (2005) 79 , P3–P3; doi: 10.1016/j.clpt.2005.12.011