Next-day residual effects of flibanserin on simulated driving performance in premenopausal women

Abstract

ObjectiveThe objective of this study was to determine the next‐day residual effects of acute and steady‐state nighttime dosing of flibanserin on simulated driving performance and cognitive function in healthy premenopausal women.MethodsIn this randomized, double‐blind, placebo‐controlled, four‐way crossover study, 72 subjects were treated with either acute oral doses of placebo, zopiclone 7.5 mg (positive control) or flibanserin 100 mg at bedtime (indicated therapeutic dose), or after chronic nightly oral doses of flibanserin 100 mg for 1 week followed by a single bedtime dose of flibanserin 200 mg (supratherapeutic dose). Simulated driving assessments were conducted 9 hr after dosing and cognitive function tests were administered immediately before or during the driving assessment.ResultsZopiclone increased standard deviation of lateral position (≥3.1 cm; p < .0001) relative to placebo and impaired other parameters previously shown to be sensitive to sedation. No impairment was detected for flibanserin at either dose relative to placebo. Flibanserin 200 mg was similar to the 100‐mg dose on cognitive testing and driving performance even though commonly reported adverse events for flibanserin were predictably increased at the higher dose.ConclusionsAt both therapeutic and supratherapeutic doses, flibanserin did not impair next‐day driving performance and cognitive function compared to placebo.

Effects of lasmiditan on simulated driving performance: Results of two randomized, blinded, crossover studies with placebo and active controls

“…Secondary endpoints were the same in both studies. Secondary driving and information processing endpoints presented in this report were selected with consideration of prior evidence of relative sensitivity to sedation effects, potential relevance to on‐road crash risk, or both (Simen et al, 2015; Kay, Hochadel, Sicard, Natarajan, & Kim, 2017). Additional driving‐related parameters obtained during the simulation included measures of lane exceedance, or the ability to stay in the lane as assessed by the number of times the vehicle's front left or right tire crosses over the lane boundary (number, maximum, duration and exceedance area); speed (average speed, speed deviation and excessive speed count); exceedance of cornering speed threshold (excessive Ay); and total number of collisions (assessed as the sum of collisions with other vehicles, off‐road crashes and number of lane deviations exceeding 4 ft, viewed as a crash‐likely event).…”

Evaluation method regarding the effect of psychotropic drugs on driving performance: A literature review

“…Most ORT are carried out in the Netherlands, which means that laboratory tests are increasing worldwide. Recently, flibanserin was approved by the FDA after its safety was confirmed using a DS thus, DS may be used much more frequently in the near future. The only method that has been standardized and verified in terms of its reliability and validity is HDT, and the only evaluation index that has been established is SDLP.…”

Protocol for the development and validation of a driving simulator for evaluating the influence of drugs on driving performance

“…Because this is an exploratory study, the sample size was set to 24 participants in reference to the sample size of previous studies conducted to confirm the validity of a DS. [6,12] The inclusion criteria are: age between 21 and 65 years; body mass index between 18.5 and 24.9 kg/m 2 ; active-type aldehyde dehydrogenase (ALDH) gene polymorphism (ALDH 2∗1/∗1); alcohol consumption >2 days a month; able to drink a prespecified amount of alcohol in 30 minutes; possession of a driver's license and driving daily for >3 years; consistent sleeping pattern (wake up between 06:00 and 09:00 am , go to bed between 21:00 and 00:00 pm ); no visual impairments; able to operate a DS with a full understanding of all DS tasks; judged by a physician as being able to participate; and able to provide written informed consent before the examination begins. The exclusion criteria are: having a disease recognized as being nonhealthy by a physician; a history of drug or food allergies; 3) serious allergic predispositions; 4) a history of stroke, head trauma, epilepsy, or malignant tumor; more than a 3-month history of sleep disorders, a medical history of sleep apnea syndrome or restless legs syndrome, or a history of hypersomnia such as narcolepsy; use of over-the-counter drugs within 1 week after starting the practice period; use of sedative hypnotics within 4 weeks after starting the practice period; experiencing more than a 6-hour time difference within 4 weeks after starting the practice period; irregular shift work and night shift work within 4 weeks after starting the practice period; experience using the same DS evaluation method as that used in the present study; a daily routine of alcohol consumption until sleep; unable to stop drinking from 2 days before until the day of the screening test, and from 2 days before hospitalization until discharge; smoking during hospitalization; donating blood within 12 weeks; use of prescription drugs within 4 weeks after starting the practice period; a diagnosis or history of alcoholism or drug dependency; positive result from a urine drug test during screening; unable or unwilling to comply with the study protocol; and judged unsuitable for participation by a physician.…”

“…Despite considerable research on driving performance in many countries, each research facility uses different evaluation methods, such as actual vehicle tests and driving simulators (DSs). [3] Recently, results regarding the effect of sleeping pills on driving performance have been considered in devising recommended clinical dosages [4] ; however, only the evaluation system in the Netherlands using actual cars [5] and that in the United States using DSs [6] is used in drug approval applications. In particular, the evaluation of vehicle “weaving” in the lateral direction became an index of driving performance referred to as the standard deviation of lateral position (SDLP), and currently, this remains the only fully validated index.…”