05 (p: two-sided tail probability). Since these studies were not powered, all p-values were to be interpreted in the perspective of the explorative character of these trials. The plots, parameters, and analysis pertaining to the pharmacokinetic evaluations were generated using SAS release 9.1 under the Windows XP operating system. Results Baseline Characteristics A total of 36 and 54 subjects were randomized in the HV and patient studies, respectively (see table I). All received at least one dose of study medication and therefore qualified for the

all-subjects-treated population. All participants in the HV study were male, as were the majority (65%) in the patient study. The patient study sample was more racially diverse and somewhat older than the HV sample. Weight and body mass index (BMI) were comparable between Palbociclib supplier studies. In the patient study, the majority of patients (76%) were diagnosed with recurrent depression, and the number of lifetime episodes was 4.4; the mean QIDS-C total score at baseline was 15.1 (standard deviation [SD] 2.26), reflecting moderately severe depression.[31] Table I Demographic and baseline characteristics of randomized subjects Safety and Tolerability Study Selleck CB-839 1 There were no serious or severe AEs in this study. In study part I (single dose), no subjects discontinued because of

AEs. Doses of 100 mg and higher were associated with gastrointestinal AEs (nausea, vomiting, once at 200 and 250 mg) and CNS AEs (dizziness, postural dizziness, headache, and paraesthesia). The 100 mg dose was determined to be the single-dose MTD. In part II of the study (multiple dose), Org 26576 100 mg bid given for 7 days (group 3) was well tolerated by all subjects. The AEs reported most frequently in the active-treatment group included mild dizziness and mild nausea. In group 4, where an up-titration schedule to 400 mg bid was applied, Org 26576 oxyclozanide was tolerated up to doses of 225 mg bid. However, at higher doses, three subjects discontinued, two because of nausea and/or vomiting (both at 325 mg bid) and one because of dizziness (at 400 mg bid). The most common treatment-emergent AEs associated

with Org 26576 (occurring in ≥25% of subjects in the active-treatment group of any study group, and with at least 2× the incidence in the placebo group) were nausea, dizziness, and somnolence, as well as feeling drunk and postural dizziness. The MTD with titration was determined to be 225 mg bid. There were no obvious treatment-related changes observed either for individual subjects or in the summary data for clinical laboratory values, vital signs, or ECG measurements. During the dose-titration part of the study, five of six subjects taking Org 26576, but no placebo subjects, had EEG observations that were interpreted as non-specific and indicative of drowsiness. Study 2 No randomized patients experienced a serious or severe AE.