Effect of ONC201 on Cardiac Repolarization in Healthy Participants - Part 2

INTERVENTION: ONC201 (investigational drug) will be dosed, as a 125mg capsule orally Part 2: 30 XHealthy Volunteers will be dosed on 3 separate occasions (7 days apart) with each of ONC201 (dose to be determined from Part 1), Placebo and control treatment. Adherence to intervention will be via mouth check of swallowed capsule CONDITION: Cancer ‐ Any cancer Cancer;Solid Tumours;Abnormal cardiac repolarization ; ; Cancer ; Solid Tumours ; Abnormal cardiac repolarization PRIMARY OUTCOME: Assess the effects of ONC201 on cardiac repolarization[ECGs ‐ on Day ‐1, Day 1, and Day 3 post dose in each period, and at Day 14. On Day 1, safety ECGs will be acquired pre‐dose(. 1 hour prior to dosing) and at approximately 0.75, 1.0, 2, 4,75, 5, and 6 hours post dose in each treatment period.] INCLUSION CRITERIA: Male or female between 18 to 45 years of age Female must be of non‐childbearing potential Body weight greater than 50 kg, body mass inde Xbetween 18‐30 kg/m2 Healthy Volunteers who are overtly healthy as determined by medical evaluation and judgment of the investigator including medical history, PE, laboratory tests, vital signs, and cardiac monitoring. SECONDARY OUTCOME: Assess the effects of ONC201 on other ECG parameters relative to a moxifloxacin positive control and to placebo: ; Change‐from‐baseline heart rate (HR), QTcF, PR, and QRS intervals using by‐time point analysis ; • Placebo‐corrected change‐from‐baseline HR, QTcF, PR, and QRS intervals ; • Categorical outliers for QTcF, HR, PR, and QRS intervals ; • T‐wave morphology and U‐wave presence changes[ECGs ‐ on Day ‐1, Day 1, and Day 3 post dose in each period, and at Day 14. On Day 1, safety ECGs will be acquired pre‐dose(= 1 hour prior to dosing) and at approximately 0.75, 1.0, 2, 4,75, 5, and 6 hours post dose in each treatment period. ; PK parameters: (AUClast, AUCinf, Cmax, Tmax, t1/2, CL/F, Vz/F, Clast, Tlast, MPR Cmax, MPR AUClast, MPR AUCinf) measured at the following timepoints ‐ Predose (within 15 minutes prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 4.25, 4,5. 4,75, 5, 5,5, 6, 8, 10, 12, 14, 16, 24, 36 and 48, hours post each dose ] Establish assay sensitivity ‐ Relationship between the plasma concentration of moxifloxacin and the change from baseline for QTcF in order to demonstrate assay sensitivity[ECGs ‐ on Day ‐1, Day 1, and Day 3 post dose in each period, and at Day 14. On Day 1, safety ECGs will be acquired pre‐dose(= 1 hour prior to dosing) and at approximately 0.75, 1.0, 2, 4,75, 5, and 6 hours post dose in each treatment period. ; PK parameters: (AUClast, AUCinf, Cmax, Tmax, t1/2, CL/F, Vz/F, Clast, Tlast, MPR Cmax, MPR AUClast, MPR AUCinf) measured at the following timepoints ‐ Predose (within 15 minutes prior to dosing) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 4.25, 4,5. 4,75, 5, 5,5, 6, 8, 10, 12, 14, 16, 24, 36 and 48, hours post each dose ] To assess the Cmax, Tmax, AUClast, AUCinf, %AUCextrap, t1/2, CL/F, Vz/F of ONC201 and its metabolite, ONC207, following administration orally in healthy participants [PK samples: Blood samples will be taken predose (within 15 minutes prior to dosing) and at 0.25, 0.5, 0.75, 1, 1,5, 2, 2,5. 3, 4, 4.25, 4,5. 4,75, 5, 5,5. 6, 8, 10, 12, 14, 16, 24, 36 and 48 hours post each dose] To evaluate the safety and tolerability of ONC201 in healthy adult participants. [Clinical and laboratory safety parameters including: ; ‐adverse events (AEs) such as Fatigue, headache, nausea and vomiting ‐ continuously Screening through to Day 14 via physical examination and subject reported events. ; For each dosing period: ; non absolute and changes over time of hematology and clinical chemistry ‐ at Screen. Day ‐1, Day 3 and Day 14 post each dose ; Vital signs (pulse, Blood pressure.temperature and respiratory rate) using an automated vital sign machine‐ at Screen, Day ‐1, Day 2, Day 3 and Day 14 post dose ; Neurological assessments (NANO assessment) at Day ‐1, Day 2, Day 3 and Day 14 post dose ; ECG intervals at Screen, Day ‐1, Day 1, Day 2, Day 3 and Day 14 post dose]