2 Subjects and Methods 2.1 Study Design This was a single-center,
randomized, single-dose, laboratory-blinded, two-period, two-sequence, crossover study. A single oral dose of doxylamine hydrogen succinate, 12.5 mg (Dormidina®, equivalent to 8.7 mg of doxylamine base) or Alisertib 25 mg (Dormidina®, equivalent to 17.4 mg of doxylamine base), was administered under fasting conditions in each study period. Since the Physician’s Desk Reference rates doxylamine as being in pregnancy category B, it was acceptable to include women in the present study. To ensure that no carryover effect was observed, a wash-out period of 7 calendar days was observed between drug administrations, corresponding to more than 10 times the expected half-life of the moiety to be measured. It should be noted that the randomization code was not made available to the personnel in charge of the determination of plasma drug concentrations (Bioanalytical and Development ADME Department, Laboratorios del Dr. Esteve, S.A., Barcelona-Catalonia) Ulixertinib research buy until results were audited by the quality assurance department. The protocol and
the informed consent forms were approved by an independent review board (ETHIPRO) on 27 September 2012. All subjects voluntarily agreed to participate in this study and signed the informed consent form after having fully comprehended its contents and prior to initiation of study procedures. This study was performed in compliance with Good Clinical Practice . 2.2 Study Population Subject screening procedures included informed consent, inclusion/exclusion check, demography, medical history, medication history, physical examination, height, weight, body mass index and a concomitant medication check. Subjects were in good health as determined by a medical history, physical examination (including vital signs), electrocardiogram (12-lead ECG) and the usual clinical
laboratory tests (hematology, biochemistry, urinalysis) including negative HIV, hepatitis B and hepatitis C tests, negative screening almost for ethanol and drugs of abuse in urine and negative pregnancy test (for female subjects). All participating subjects were judged to be eligible for the study when assessed against the inclusion and exclusion criteria. Tolerability and safety were evaluated through assessment of adverse events (AEs), standard laboratory evaluations and vital signs. The predetermined reason for removing subjects from the study was for any safety issues as determined by the investigator. Also, subjects could be withdrawn because of protocol violations, administrative problems, difficulties in blood collection, occurrence of emesis during the time interval described in the protocol or other reasons described in the protocol. Furthermore, subjects were allowed to discontinue their participation in the study at any time.