Moxifloxacin / Six, freely moving, telemetered, female beagle dogs treated with placebo, 10, 30, and 100 mg/kg oral dose of moxifloxacin, according to a cross-over design. / Data from a double-blind, randomized, placebo- and positive-controlled, threeway crossover study in 33healthy subjects treated with placebo and a single 400-mg oral dose of moxifloxacin. Dose was given at Days 1 and 7.
PK: plasma samples were collected in a separate group of two dogs undergoing the same treatment (times: 0.5, 1, 2, 4, 6, 22 h post-dosing). One plasma sample was collected in the other six dogs 6 h post-dosing. / PK: Plasma samples were collected at times 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 h post-dosing. Additional samples were taken at 24, 36, 48, and 72 h after the last dose of Day 7. Blood samples were drawn within 5 min after each 12-lead ECG collection.
ECG: QT and RR intervals were available at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 h post-dosing. Additional 10 placebo-treated dogs were available for the PD assessment. / ECG: 25 h of continuous Holter monitoring and eleven 12-lead ECG (triplicate readings with 60-sec intervals between each 10-sec reading) were collected on Day 0 (pre-treatment), Day 1, and Day 7, with 4 additional 12-lead ECG recordings at 24 and 36 h (Day 8), 48 h (Day 9), and 72 h (Day 10) after the last dose on Day 7.Times in Days 0, 1, and 7: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 h
Carisbamate / Six, conscious, telemetered, male beagle dogs treated with placebo (Day 1), 15 mg/kg (Day 4), 30 mg/kg (Day 8), and 60 mg/kg (Day 11) of carisbamate. / Data from a double-blind, randomized, placebo- and positive-controlled, three-way crossover study in 37healthy subjects treated with placebo, 250 mg b.i.d. (500 mg/day) on Days 1 and 2, 500 mg b.i.d. (1,000 mg/day) on Days 3 and 4, and 750 mg b.i.d. (1,500 mg/day) on Days 5 and 6 of carisbamate. A final dose of 750 mg was given the morning of Day 7.
PK: blood samples were taken pre-dose and at 0.5, 1, 2, 3 (prior to removal from the sling restraint) and 6 h post-dosing. / PK: see Moxifloxacin – Humans PK
ECG: lead II ECG variables were extracted at -28, 28, 58, 90, 118, 150, 178, 240, 300, and 350 min post-dosing. / ECG: see Moxifloxacin – Humans ECG
MAO-inhibitor / Eight, conscious, telemetered, female beagle dogs: four of them received placebo and four of them received 10 mg/kg of MAO-inhibitor. / Data from a double-blind, placebo-controlled, randomized, crossover study in 42healthy females treated with placebo or 750 mg of MAO-inhibitor (Period 1 and 2).
PK: Blood samples were taken at 0.5, 1, and 4 h post-dosing. / PK: Plasma samples were collected on Day 1 at 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, and 48 h after dose administration.
ECG: QT and RR intervals were automatically calculated, using six to seven leads, before (0.25 and 0 h) and after the administration of the solvent or compound (times: 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4 h). / ECG: Serial assessments of 12-lead ECG recordings were made. Continuous ECG recordings were made on Day -1, from 24 to 12 h before dose administration (12 samples) and on Day 1 from 0.5 h before dose administration until 12 h post-dosing (16 samples).
Serdemetan / Six, conscious, telemetered, female beagle dogs orally treated with placebo and 20 mg/kg of serdemetan. The dogs were positioned in slings for 6 h, then they were transferred to their pens for 18 h. / Data from a first-in-human, open label, phase 1, dose-escalation study in 71 subjects with advanced stage and/or refractory solid tumors or lymphoma. The following dose levels and schedules were assessed: once daily dosing (4 mg [n = 4], 8 mg [n = 3], 20 mg [n = 3], 40 mg [n = 4], 60 mg [n = 4], 90 mg [n = 4], 150 mg [n = 4], 225 mg [n = 7], 300 mg [n = 16], 350 mg [n = 8], and 400 mg [n = 3]) and twice a day dosing (150 mg [n = 8] and 200 mg [n = 3]). Subjects received at least one dose of serdemetan.
PK: Blood samples were taken at 2, 4, 6, and 24 h post-dosing / PK: Doses were given once daily. Blood samples were drawn on Days 1 (times: 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 h), 3 and 10 (time: 0 h), and 21 (times: 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 h). Blood collection was done within 15 min after ECG.
ECG: data were measured before (0 h), every 30 min during the measurement period in the slings (first 6 h), and every 60 min during the period in the pen (32 observation/dog). / ECG: 12-lead ECG parameters were measured from pre-dosing to all post-dosing time points.
Table 1S: PK and ECG details for each compound and species.