{"classes":[{"categories":[{"measurements":[{"groupId":"OG000","spread":"0","value":"6.00"},{"groupId":"OG001","spread":"69.3","value":"3.33"},{"groupId":"OG002","spread":"90.4","value":"10.4"},{"groupId":"OG003","spread":"87.7","value":"3.01"},{"groupId":"OG004","spread":"35.0","value":"1.67"},{"groupId":"OG005","spread":"65.8","value":"3.02"},{"groupId":"OG006","spread":"41.7","value":"3.78"},{"groupId":"OG007","spread":"24.4","value":"4.66"},{"groupId":"OG008","spread":"57.7","value":"4.00"},{"groupId":"OG009","spread":"41.7","value":"3.65"},{"groupId":"OG010","spread":"83.9","value":"3.25"},{"groupId":"OG011","spread":"46.5","value":"2.73"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"3"},{"groupId":"OG003","value":"3"},{"groupId":"OG004","value":"3"},{"groupId":"OG005","value":"4"},{"groupId":"OG006","value":"9"},{"groupId":"OG007","value":"3"},{"groupId":"OG008","value":"4"},{"groupId":"OG009","value":"6"},{"groupId":"OG010","value":"4"},{"groupId":"OG011","value":"3"}],"units":"Participants"}],"title":"Tmax: Day 1"},{"categories":[{"measurements":[{"groupId":"OG000","spread":"125","value":"1.67"},{"groupId":"OG001","spread":"88.2","value":"3.00"},{"groupId":"OG002","spread":"50.0","value":"4.00"},{"groupId":"OG003","spread":"69.3","value":"3.33"},{"groupId":"OG004","spread":"136","value":"9.31"},{"groupId":"OG005","spread":"44.7","value":"4.00"},{"groupId":"OG006","spread":"108","value":"5.41"},{"groupId":"OG007","spread":"37.7","value":"4.41"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"3"},{"groupId":"OG003","value":"3"},{"groupId":"OG004","value":"3"},{"groupId":"OG005","value":"4"},{"groupId":"OG006","value":"9"},{"groupId":"OG007","value":"3"},{"groupId":"OG008","value":"0"},{"groupId":"OG009","value":"0"},{"groupId":"OG010","value":"0"},{"groupId":"OG011","value":"0"}],"units":"Participants"}],"title":"Tmax: Day 21"},{"categories":[{"measurements":[{"groupId":"OG008","spread":"58.6","value":"2.33"},{"groupId":"OG009","spread":"49.5","value":"6.00"},{"groupId":"OG010","spread":"63.9","value":"2.80"},{"groupId":"OG011","spread":"34.7","value":"4.33"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"},{"groupId":"OG003","value":"0"},{"groupId":"OG004","value":"0"},{"groupId":"OG005","value":"0"},{"groupId":"OG006","value":"0"},{"groupId":"OG007","value":"0"},{"groupId":"OG008","value":"4"},{"groupId":"OG009","value":"6"},{"groupId":"OG010","value":"4"},{"groupId":"OG011","value":"3"}],"units":"Participants"}],"title":"Tmax: Day 28"},{"categories":[{"measurements":[{"groupId":"OG000","spread":"1.05","value":"23.5"},{"groupId":"OG001","spread":"3.23","value":"22.5"},{"groupId":"OG002","spread":"11.9","value":"21.1"},{"groupId":"OG003","spread":"7.15","value":"22.7"},{"groupId":"OG004","spread":"13.0","value":"22.6"},{"groupId":"OG005","spread":"2.14","value":"23.4"},{"groupId":"OG006","spread":"50.6","value":"16.4"},{"groupId":"OG007","spread":"6.78","value":"22.4"},{"groupId":"OG008","spread":"2.79","value":"23.2"},{"groupId":"OG009","spread":"34.8","value":"20.0"},{"groupId":"OG010","spread":"45.6","value":"18.5"},{"groupId":"OG011","spread":"1.29","value":"5.96"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"2"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"3"},{"groupId":"OG003","value":"3"},{"groupId":"OG004","value":"3"},{"groupId":"OG005","value":"4"},{"groupId":"OG006","value":"9"},{"groupId":"OG007","value":"3"},{"groupId":"OG008","value":"4"},{"groupId":"OG009","value":"6"},{"groupId":"OG010","value":"4"},{"groupId":"OG011","value":"15"}],"units":"Participants"}],"title":"Tlast: Day 1"},{"categories":[{"measurements":[{"groupId":"OG000","spread":"35.2","value":"160"},{"groupId":"OG001","spread":"0.998","value":"194"},{"groupId":"OG002","spread":"25.4","value":"170"},{"groupId":"OG003","spread":"43.8","value":"170"},{"groupId":"OG004","spread":"39.7","value":"120"},{"groupId":"OG005","spread":"31.1","value":"160"},{"groupId":"OG006","spread":"26.6","value":"183"},{"groupId":"OG007","spread":"60.2","value":"120"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"3"},{"groupId":"OG003","value":"3"},{"groupId":"OG004","value":"3"},{"groupId":"OG005","value":"4"},{"groupId":"OG006","value":"10"},{"groupId":"OG007","value":"3"},{"groupId":"OG008","value":"0"},{"groupId":"OG009","value":"0"},{"groupId":"OG010","value":"0"},{"groupId":"OG011","value":"0"}],"units":"Participants"}],"title":"Tlast: Day 21"},{"categories":[{"measurements":[{"groupId":"OG008","spread":"0","value":"24.0"},{"groupId":"OG009","spread":"22.8","value":"22.0"},{"groupId":"OG010","spread":"0.309","value":"24.0"},{"groupId":"OG011","spread":"57.5","value":"17.9"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"},{"groupId":"OG003","value":"0"},{"groupId":"OG004","value":"0"},{"groupId":"OG005","value":"0"},{"groupId":"OG006","value":"0"},{"groupId":"OG007","value":"0"},{"groupId":"OG008","value":"4"},{"groupId":"OG009","value":"6"},{"groupId":"OG010","value":"4"},{"groupId":"OG011","value":"3"}],"units":"Participants"}],"title":"Tlast: Day 28"},{"categories":[{"measurements":[{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG000","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG001","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG002","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG003","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG004","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG005","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG006","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG007","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG008","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG009","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG010","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG011","spread":"NA","value":"NA"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"3"},{"groupId":"OG003","value":"3"},{"groupId":"OG004","value":"3"},{"groupId":"OG005","value":"4"},{"groupId":"OG006","value":"10"},{"groupId":"OG007","value":"3"},{"groupId":"OG008","value":"4"},{"groupId":"OG009","value":"6"},{"groupId":"OG010","value":"4"},{"groupId":"OG011","value":"15"}],"units":"Participants"}],"title":"t½,z: Day 1"},{"categories":[{"measurements":[{"groupId":"OG000","spread":"19.5","value":"89.5"},{"groupId":"OG001","spread":"35.2","value":"79.5"},{"groupId":"OG002","spread":"4.35","value":"71.7"},{"groupId":"OG003","spread":"18.2","value":"68.4"},{"groupId":"OG004","spread":"32.3","value":"57.3"},{"groupId":"OG005","spread":"24.0","value":"63.7"},{"groupId":"OG006","spread":"16.4","value":"77.3"},{"groupId":"OG007","spread":"0","value":"150"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"3"},{"groupId":"OG003","value":"3"},{"groupId":"OG004","value":"3"},{"groupId":"OG005","value":"4"},{"groupId":"OG006","value":"10"},{"groupId":"OG007","value":"3"},{"groupId":"OG008","value":"0"},{"groupId":"OG009","value":"0"},{"groupId":"OG010","value":"0"},{"groupId":"OG011","value":"0"}],"units":"Participants"}],"title":"t½,z: Day 21"},{"categories":[{"measurements":[{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG008","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG009","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG010","spread":"NA","value":"NA"},{"comment":"Last sampling time was 24 hrs after dosing on day 1 \\& 28. This limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","groupId":"OG011","spread":"NA","value":"NA"}]}],"denoms":[{"counts":[{"groupId":"OG000","value":"0"},{"groupId":"OG001","value":"0"},{"groupId":"OG002","value":"0"},{"groupId":"OG003","value":"0"},{"groupId":"OG004","value":"0"},{"groupId":"OG005","value":"0"},{"groupId":"OG006","value":"0"},{"groupId":"OG007","value":"0"},{"groupId":"OG008","value":"4"},{"groupId":"OG009","value":"6"},{"groupId":"OG010","value":"4"},{"groupId":"OG011","value":"15"}],"units":"Participants"}],"title":"t½,z: Day 28"}],"denoms":[{"counts":[{"groupId":"OG000","value":"3"},{"groupId":"OG001","value":"3"},{"groupId":"OG002","value":"3"},{"groupId":"OG003","value":"3"},{"groupId":"OG004","value":"3"},{"groupId":"OG005","value":"4"},{"groupId":"OG006","value":"10"},{"groupId":"OG007","value":"3"},{"groupId":"OG008","value":"4"},{"groupId":"OG009","value":"6"},{"groupId":"OG010","value":"4"},{"groupId":"OG011","value":"15"}],"units":"Participants"}],"description":"Plasma samples were collected and used for pharmacokinetics (PK) assessments.\n\nMean values of PK parameters are presented with the coefficient of variation (CV%)","dispersionType":"Standard Deviation","groups":[{"description":"All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 20 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle.","id":"OG000","title":"Phase 1, Schedule A: 20 mg"},{"description":"All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 40 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle","id":"OG001","title":"Phase 1, Schedule A: 40 mg"},{"description":"All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 80 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle","id":"OG002","title":"Phase 1, Schedule A: 80 mg"},{"description":"All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 120 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle","id":"OG003","title":"Phase 1, Schedule A: 120 mg"},{"description":"All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 180 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle","id":"OG004","title":"Phase 1, Schedule A: 180 mg"},{"description":"All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 270 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle","id":"OG005","title":"Phase 1, Schedule A: 270 mg"},{"description":"All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 300 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle","id":"OG006","title":"Phase 1, Schedule A: 300 mg"},{"description":"All participants in Phase I, Schedule A, who received NMS-03592088 at the starting dose of 360 mg administered orally once daily for 21 consecutive days followed by 7 days of rest in a 28-day cycle","id":"OG007","title":"Phase 1, Schedule A: 360 mg"},{"description":"All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 120 mg administered orally once daily for 28 consecutive days, in a 28-day cycle.","id":"OG008","title":"Phase 1, Schedule B: 120 mg"},{"description":"All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 180 mg administered orally once daily for 28 consecutive days, in a 28-day cycle","id":"OG009","title":"Phase 1, Schedule B: 180 mg"},{"description":"All participants in Phase I, Schedule B, who received NMS-03592088 at the starting dose of 250 mg administered orally once daily for 28 consecutive days, in a 28-day cycle","id":"OG010","title":"Phase 1, Schedule B: 250 mg"},{"description":"Participants who had failed standard of care including Venetoclax and Gilteritining based therapies.\n\nNMS-03592088 was administered, on Cycle 1, at 360 mg/day (loading dose) for 5 consecutive days, followed by 150 mg/day (maintenance dose) for 23 consecutive days. The same maintenance dose (150 mg/day) was administered from Cycle 2 onwards","id":"OG011","title":"Phase 2, Schedule B: 360+150 mg"}],"paramType":"MEAN","populationDescription":"Participants evaluable for PK analysis (participants with sufficient samples to provide interpretable results). The plasma PK of NMS-03592088 and NMS-03593860 and NMS-03603422 were collected for PK profile.\n\nSchedule B involved 28 days continuous treatment. Last sampling time was 24 hrs after dosing on day 1 \\& 28.\n\nThis limited sampling times didn't allow calculation of t½, of the terminal phase, characterised by long half-lives, shown by data from schedule A. Hence evaluation was not performed.","reportingStatus":"POSTED","timeFrame":"Schedule A: Day 1 and 21 Schedule B: Day 1 and 28","title":"Pharmacokinetic Parameters: Time to Maximum Plasma Concentration (Tmax), Time to Last Measurable Concentration (Tlast), and Terminal Elimination Half-life (t½,z) of NMS-03592088","type":"SECONDARY","unitOfMeasure":"hour"}