{"classes":[{"categories":[{"measurements":[{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG000","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG001","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG002","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG003","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG004","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG005","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG006","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG007","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG008","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG009","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG010","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","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":"CL/F: Day 1"},{"categories":[{"measurements":[{"groupId":"OG000","spread":"53.1","value":"7.02"},{"groupId":"OG001","spread":"57.1","value":"20.4"},{"groupId":"OG002","spread":"34.6","value":"19.0"},{"groupId":"OG003","spread":"52.5","value":"27.6"},{"groupId":"OG004","spread":"46.5","value":"21.4"},{"groupId":"OG005","spread":"26.3","value":"12.1"},{"groupId":"OG006","spread":"46.5","value":"16.8"},{"groupId":"OG007","spread":"0","value":"4.94"}]}],"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":"CL/F: Day 21"},{"categories":[{"measurements":[{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG008","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG009","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","groupId":"OG010","spread":"NA","value":"NA"},{"comment":"The half-life of the molecule was many times longer than 24h so it was not possible to estimate it at all for Schedule B due to the 24h sampling. This implied that the parameter CL/F could not be calculated","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":"CL/F: Day 28"},{"categories":[{"measurements":[{"groupId":"OG000","spread":"19.9","value":"399"},{"groupId":"OG001","spread":"32.2","value":"318"},{"groupId":"OG002","spread":"23.3","value":"372"},{"groupId":"OG003","spread":"41.6","value":"434"},{"groupId":"OG004","spread":"57.5","value":"301"},{"groupId":"OG005","spread":"44.7","value":"264"},{"groupId":"OG006","spread":"117","value":"477"},{"groupId":"OG007","spread":"126","value":"502"},{"groupId":"OG008","spread":"89.3","value":"317"},{"groupId":"OG009","spread":"31.4","value":"263"},{"groupId":"OG010","spread":"97.1","value":"359"},{"groupId":"OG011","spread":"45.0","value":"1820"}]}],"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":"CLss/F: Day 1"},{"categories":[{"measurements":[{"groupId":"OG000","spread":"40.8","value":"39.9"},{"groupId":"OG001","spread":"42.5","value":"91.2"},{"groupId":"OG002","spread":"26.3","value":"85.7"},{"groupId":"OG003","spread":"38.6","value":"110"},{"groupId":"OG004","spread":"38.7","value":"74.7"},{"groupId":"OG005","spread":"23.1","value":"50.9"},{"groupId":"OG006","spread":"38.4","value":"77.8"},{"groupId":"OG007","spread":"50.4","value":"98.2"}]}],"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":"CLss/F: Day 21"},{"categories":[{"measurements":[{"groupId":"OG008","spread":"46.8","value":"57.4"},{"groupId":"OG009","spread":"35.5","value":"56.3"},{"groupId":"OG010","spread":"52.7","value":"63.8"},{"groupId":"OG011","spread":"117","value":"209"}]}],"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":"CLss/F: 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. Mean 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\nThe half-life of the molecule was many times longer than 24 hours, so it was not possible to estimate it at all for Schedule B due to the 24-hour sampling. This implied that the parameter CL/F could not be calculated","reportingStatus":"POSTED","timeFrame":"Schedule A: Day 1 and Day 21 Schedule B: Day 1 and Day 28 CL/F: Evaluation of CL/F for Day 1 of all arms in Schedule A and Schedule B and Day 28 of Schedule B has not been performed","title":"Pharmacokinetic Parameters: Apparent Plasma Clearance (CL/F) and Apparent Plasma Clearance at Steady State (CLss/F)","type":"SECONDARY","unitOfMeasure":"L/h"}