Intermezzo zolpidem: Preliminary Phase I data

Preliminary data from a double-blind, active- and placebo-controlled, 4-way crossover Phase I highway driving study in 40 healthy volunteers showed that 3.5 mg Intermezzo led to no significant next morning effects on SDLP in a highway driving lane on any of 20 different thresholds ranging from 1.75 to 6.5 cm at 4 hours after middle of the night dosing as measured by a symmetry analysis, the primary statistical analysis. Transcept said there is no commonly accepted change in SDLP that identifies a driver as being impaired. Based on a review of published literature, an SDLP change of 2.5 cm was specified in the protocol as the primary threshold of impairment for statistical analyses, which the company said is approximately equal to the mean increase in SDLP reported to occur with a blood alcohol concentration of 0.05%. FDA previously informed Transcept that the symmetry analysis was a "reasonable approach" to measure potential next morning driving impairment. Transcept's proposed labeling for Intermezzo states that patients have at least 4 hours remaining in bed after middle of the night dosing.

At 3 hours after middle of the night dosing with Intermezzo, a significant reduction in driving performance was observed at SDLP thresholds ranging from 1.75 to 4 cm. The active-control zopiclone, which was used to establish that the analysis was capable of detecting driving impairment, administered at bedtime 9 hours prior to driving also significantly reduced driving performance at SDLP thresholds ranging from 1.75 to 5.5 cm. Transcept also conducted a secondary analysis of SDLP to compared the means of each active treatment arm to placebo. Mean differences in SDLP from placebo were 0.8, 1.5 and 2.5 cm for Intermezzo administered 3 hours prior to driving, Intermezzo administered 4 hours prior to driving, and zopiclone administered 9 hours prior to driving, respectively. The company said the mean differences in SDLP compared to placebo were relatively small when compared with historical data for FDA-approved hypnotics. SDLP was measured as subjects drove an automobile at 60 mph for 62 miles on a public highway under normal traffic conditions. ...