- Phase 1 Dose Escalation: Investigator Assessed Overall Response Rate (ORR) by Total Daily Dose [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the dose escalation phase was 5.0 months (range 0.4 to 34.2 months). ]
ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, marrow CR (mCR) (for MDS) and MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS.
CR:
- ANC > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
CRi:
- All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L
CRp:
- All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
PR:
- Meets hematologic criteria of CR
- Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%.
MLFS:
- Bone marrow blasts < 5%
- Absence of blasts with Auer rods
- Absence of extramedullary disease
- No hematologic recovery required
mCR:
- Bone marrow myeloblasts ≤ 5% and decreased by ≥ 50%
- Phase 1 Dose Expansion: Investigator Assessed Overall Response Rate (ORR) [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months). ]
ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, mCR (for MDS), or MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS.
CR:
- ANC > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
CRi:
- All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L
CRp:
- All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
PR:
- Meets hematologic criteria of CR
- Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%.
MLFS:
- Bone marrow blasts < 5%
- Absence of blasts with Auer rods
- Absence of extramedullary disease
- No hematologic recovery required
mCR:
- Bone marrow myeloblasts ≤ 5% and decreased by ≥ 50%
- Combined Phase 1/2: Investigator Assessed Overall Response Rate in Participants With R/R AML [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure for Phase 1 and 2 R/R AML participants was 5.4 months (range 0.4 to 34.2 months). ]
For participants with R/R AML ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML.
CR:
- ANC > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
CRi:
- All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L
CRp:
- All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
PR:
- Meets hematologic criteria of CR
- Decrease of BM blasts to 5-25% and decrease of pretreatment BM blast ≥ 50%.
MLFS:
- Bone marrow blasts < 5%
- Absence of blasts with Auer rods
- Absence of extramedullary disease
- No hematologic recovery required
- Phase 1 Dose Escalation: Complete Response Rate (CRR) by Total Daily Dose [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months). ]
Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS as assessed by the investigator.
CR for AML:
- Absolute neutrophil count (ANC) > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
CR for MDS:
- Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines
- Peripheral blood:
- Hemoglobin ≥ 11 g/dL
- Platelets ≥ 100 × 10⁹/L
- Neutrophils ≥ 1.0 × 10⁹/L
- Blasts = 0%
- Phase 1 Dose Expansion: Complete Response Rate [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months). ]
Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS as assessed by the investigator.
CR for AML:
- Absolute neutrophil count (ANC) > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
CR for MDS:
- Bone marrow: ≤ 5% myeloblasts with normal maturation of all cell lines
- Peripheral blood:
- Hemoglobin ≥ 11 g/dL
- Platelets ≥ 100 × 10⁹/L
- Neutrophils ≥ 1.0 × 10⁹/L
- Blasts = 0%
- Phase 2 Dose Expansion: Complete Response Rate [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months). ]
Complete response rate is defined as the percentage of participants achieving a complete response (CR) based on the 2003 revised IWG criteria for AML as assessed by the investigator.
CR for AML:
- Absolute neutrophil count (ANC) > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
- Phase 1 Dose Escalation: Rate of Complete Response and Complete Response With Incomplete Hematological Recovery (CR/CRi/CRp) by Total Daily Dose [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months). ]
The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp), based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator review.
CR:
- ANC > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
CRi:
- All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L
CRp:
- All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
- Phase 1 Dose Expansion: Rate of Complete Response and Complete Responses With Incomplete Hematological Recovery (CR/CRi/CRp) [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months). ]
The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp) based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS, assessed by the investigator.
CR:
- ANC > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
CRi:
- All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L
CRp:
- All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
- Phase 2 Dose Expansion: Rate of Complete Response and Complete Responses With Incomplete Hematological Recovery (CR/CRi/CRp) [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months). ]
The percentage of participants achieving a complete response (CR), CR with incomplete neutrophil recovery (CRi), or a CR with incomplete platelet recovery (CRp) based on the 2003 revised IWG criteria for AML, assessed by the Investigator.
CR:
- ANC > 1.0 x10⁹/L
- Platelet count > 100 x10⁹/L
- Bone marrow (BM) blasts < 5%
- Absence of blasts with Auer rods
- Independence of red cell transfusions
CRi:
- All CR criteria except for residual neutropenia (ANC < 1.0 x 10⁹/L
CRp:
- All CR criteria except for residual thrombocytopenia (platelet counts < 100 x 10⁹/L)
- Phase 1 Dose Expansion: Kaplan-Meier Estimate of Duration of Response (DOR) [ Time Frame: From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months). ]
Among participants who had a response of CR, CRi, CRp, PR, mCR, or MLFS based on the 2003 revised IWG criteria for AML or the 2006 modified IWG criteria for MDS, assessed by the Investigator, duration of response was calculated from the date of the first occurrence of response to the date of documented disease relapse, progression, or death due to any cause, whichever occurred first. DOR was estimated using the Kaplan-Meier method.
Participants without relapse, progressive disease, or death due to any cause were censored at the date of the last adequate response assessment.
- Phase 2 Dose Expansion: Kaplan-Meier Estimate of Duration of Response [ Time Frame: From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months). ]
For participants with an objective response based on the 2003 revised IWG criteria for AML assessed by the Investigator, duration of response was calculated from the date of the first occurrence of response to the date of documented disease relapse, progression, or death due to any cause, whichever occurred first. Participants without relapse, progressive disease or death were censored at the last response assessment date.
Relapse (for participants who previously attained CR, Cri, CRp or MLFS): BM blasts ≥ 5%, reappearance of blasts in the blood or development of extramedullary disease.
Disease progression (for participants who previously attained PR): development of new extramedullary disease, or
For participants with 5% to 67% BM blasts at nadir:
- a > 50% increase in BM blasts from nadir and that is ≥ 20%.
For participants with ≥ 67% BM blasts at nadir:
- a doubling of the nadir absolute peripheral blood (PB) blast count and the final absolute PB blast count > 10 x 10⁹/L.
- Phase 1 Dose Expansion: Kaplan-Meier Estimate of Overall Survival [ Time Frame: From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months). ]
Overall survival is defined as the time from first dose to the date of death due to any cause. Participants still alive were censored at the last date known to be alive or at the data cut-off date, whichever was earlier.
- Phase 2 Dose Expansion: Kaplan-Meier Estimate of Overall Survival [ Time Frame: From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months). ]
Overall survival is defined as the time from first dose to the date of death due to any cause. Participants still alive were censored at the last date known to be alive or at the data cut-off date, whichever was earlier.
- Phase 1 Combined: Percentage of Participants Who Achieved 56-Day Red Blood Cell Transfusion Independence Post-baseline [ Time Frame: Baseline to the end of treatment; overall median duration of treatment exposure in Phase 1 combined was 5.1 months (range 0.4, 34.2 months). ]
Participants who achieved 56-day post-baseline red blood cell (RBC) transfusion independence, i.e. with no RBC transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline RBC transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 28 days before and 28 days after the first dose of treatment for Phase 1.
Results are reported for all participants in Phase 1 combined and for the subset of participants with R/R AML.
- Phase 1 Combined: Percentage of Participants Who Achieved 56-Day Platelet Transfusion Independence Post-baseline [ Time Frame: Baseline to the end of treatment; overall median duration of treatment exposure in Phase 1 combined was 5.1 months (range 0.4, 34.2 months). ]
Participants who achieved 56-day post-baseline platelet transfusion independence, i.e. with no platelet transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline platelet transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 28 days before and 28 days after the first dose of treatment for Phase 1.
Results are reported for all participants in Phase 1 combined and for the subset of participants with R/R AML.
- Phase 2: Percentage of Participants Who Achieved 56-Day Red Blood Cell Transfusion Independence Post-baseline [ Time Frame: Baseline to the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months). ]
Participants who achieved 56-day post-baseline red blood cell (RBC) transfusion independence, i.e. with no RBC transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline RBC transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 56 days before the first dose date for Phase 2.
- Phase 2: Percentage of Participants Who Achieved 56-Day Platelet Transfusion Independence Post-baseline [ Time Frame: Baseline to the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months). ]
Participants who achieved 56-day post-baseline platelet transfusion independence, i.e. with no platelet transfusions for at least 56 consecutive days during the treatment exposure period, reported by Baseline platelet transfusion dependence status. Participants with at least one transfusion during the Baseline period were considered transfusion dependent at Baseline, where the Baseline period is defined as 56 days before the first dose date for Phase 2.
- Phase 1 Dose Expansion: Kaplan-Meier Estimate of Event Free Survival (EFS) [ Time Frame: From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months). ]
Event-free survival is defined as the interval from the date of the first dose to the date of documented relapse, progression, or death due to any cause, whichever occurs first. Participants without an EFS event were censored at the date of the last adequate response assessment.
- Phase 2 Dose Expansion: Kaplan-Meier Estimate of Event Free Survival [ Time Frame: From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months). ]
Event-free survival is defined as the interval from the date of the first dose to the date of documented relapse, progression, or death due to any cause, whichever occurred first. Participants without an EFS event were censored at the date of the last adequate response assessment.
- Phase 1 Dose Expansion: Kaplan-Meier Estimate of Duration of Complete Response (DOCR) [ Time Frame: From first dose of study treatment to the data cut-off date of 01 September 2017; overall median time on follow-up in Phase 1 Dose Expansion was 8.3 months (range 0.5 to 32.8 months). ]
Among participants who had a response of CR based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS assessed by the Investigator, duration of complete response was calculated from the date of the first occurrence of complete response to the date of documented disease relapse, progression or death, whichever occurred earlier. DOCR was estimated using the Kaplan-Meier method.
Participants without relapse, progressive disease, or death due to any cause were censored at the date of the last adequate response assessment.
- Phase 2 Dose Expansion: Duration of Complete Response [ Time Frame: From first dose of study treatment to the data cut-off date of 01 September 2017; median time on follow-up in Phase 2 was 5.8 months (range 0.4 to 22.5 months). ]
Among participants who had a response of CR based on the 2003 revised IWG criteria for AML assessed by the Investigator, duration of complete response was calculated from the date of the first occurrence of complete response to the date of documented disease relapse, progression or death, whichever occurred earlier. DOCR was estimated using the Kaplan-Meier method.
Participants without relapse, progressive disease, or death due to any cause were censored at the date of the last adequate response assessment.
- Phase 1 Dose Escalation: Time to First Response by Total Daily Dose [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months). ]
Time to response is defined as the time from the date of first dose to the date of the first occurrence of response of CR, CRi, CRp, PR, mCR (for MDS) or MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS as assessed by the Investigator.
- Phase 1 Dose Expansion: Time to First Response [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months). ]
Time to response is defined as the time from the date of first dose to the date of the first occurrence of response of CR, CRi, CRp, PR, mCR (for MDS) or MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS as assessed by the Investigator.
- Phase 2 Dose Expansion: Time to First Response [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months). ]
Time to response is defined as the time from the date of first dose to the date of the first occurrence of response of CR, CRi, CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML as assessed by the Investigator.
- Phase 1 Dose Escalation: Time to Best Response by Total Daily Dose [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 1 Dose Escalation was 5.0 months (range 0.4 to 34.2 months). ]
Time to best response is defined as the time from the date of the first dose to the date of the first occurrence of best response according to the following hierarchical order: CR, CRi/CRp, PR, mCR (for MDS) / MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator assessment.
- Phase 1 Dose Expansion: Time to Best Response [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Part 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months). ]
Time to best response is defined as the time from the date of the first dose to the date of the first occurrence of best response according to the following hierarchical order: CR, CRi/CRp, PR, mCR (for MDS) / MLFS (for AML) based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator assessment.
- Phase 2 Dose Expansion: Time to Best Response [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months). ]
Time to best response is defined as the time from the date of the first dose to the date of the first occurrence of best response according to the following hierarchical order: CR, CRi/CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML per investigator assessment.
- Phase 1 Dose Escalation: Time to Complete Response by Total Daily Dose [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in the Phase 1 Dose Escalation phase was 5.0 months (range 0.4 to 34.2 months). ]
Time to complete response is defined as the time from the date of the first dose to the date of the first complete response based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator assessment.
- Phase 1 Dose Expansion: Time to Complete Response [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Part 1 Dose Expansion was 5.2 months (range 0.5 to 32.8 months). ]
Time to complete response is defined as the time from the date of the first dose to the date of the first complete response based on the 2003 revised IWG criteria for AML and 2006 modified IWG criteria for MDS per investigator assessment.
- Phase 2 Dose Expansion: Time to Complete Response [ Time Frame: Response assessments were performed every 28 days through Month 12 and every 56 days thereafter until the end of treatment; median duration of treatment exposure in Phase 2 was 5.3 months (range 0.4 to 22.5 months). ]
Time to complete response is defined as the time from the date of the first dose to the date of the first complete response based on the 2003 revised IWG criteria for AML per investigator assessment.
- Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to 8 Hours Postdose (AUC0-8) of Enasidenib After a Single Oral Dose on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Dose Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for assessment of enasidenib pharmacokinetics (PK).
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.
- Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to 10 Hours Postdose (AUC0-10) of Enasidenib After a Single Oral Dose on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 10 hours post-dose (AUC0-10) was calculated using the linear trapezoidal rule.
- Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours Postdose (AUC0-24) of Enasidenib After a Single Oral Dose on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.
- Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to 72 Hours Postdose (AUC0-72) of Enasidenib After a Single Oral Dose on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 72 hours post-dose (AUC0-72) was calculated using the linear trapezoidal rule.
- Phase 1: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Enasidenib After a Single Oral Dose on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.
- Phase 1: Maximum Concentration of Enasidenib After a Single Oral Dose on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1: Time to Maximum Concentration (Tmax) of Enasidenib After a Single Oral Dose on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1: Apparent Terminal Phase Half-life (t½) of Enasidenib After a Single Oral Dose on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
T1/2 was not calculated when the terminal elimination rate constant (λz) was not estimable.
- Phase 1: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of Enasidenib After Multiple Oral Doses [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.
- Phase 1: AUC From Time Zero to 10 Hours Postdose (AUC0-10) of Enasidenib After Multiple Oral Doses [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 10 hours post-dose (AUC0-10) was calculated using the linear trapezoidal rule.
- Phase 1: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Enasidenib After Multiple Oral Doses [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.
- Phase 1: Maximum Concentration (Cmax) of Enasidenib After Multiple Oral Doses [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1: Time to Maximum Concentration (Tmax) of Enasidenib After Multiple Oral Doses [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 2: Area Under the Plasma Concentration Time Curve From Time Zero to 8 Hours Postdose (AUC0-8) of Enasidenib After Single and Multiple Oral Doses [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, and 8 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) of enasidenib was calculated using the linear trapezoidal rule.
- Phase 2: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours Postdose (AUC 0-24) of Enasidenib After Single and Multiple Oral Doses [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.
- Phase 2: Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Enasidenib After Single and Multiple Oral Doses [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.
- Phase 2: Maximum Concentration (Cmax) of Enasidenib After Single and Multiple Oral Doses [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 2: Time to Maximum Concentration (Tmax) of Enasidenib After Single and Multiple Oral Doses [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 2: Apparent Terminal Phase Half-life (t1/2) of Enasidenib After Single and Multiple Oral Doses [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to hour 8 post-dose (AUC 0-8) was calculated using the linear trapezoidal rule.
- Phase 1: AUC From Time Zero to 10 Hours Postdose (AUC0-10) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 10 hours post-dose (AUC0-10) was calculated using the linear trapezoidal rule.
- Phase 1: AUC From Time Zero to 24 Hours Postdose (AUC0-24) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.
- Phase 1: AUC From Time Zero to 72 Hours Postdose (AUC0-72) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 72 hours post-dose (AUC0-72) was calculated using the linear trapezoidal rule.
- Phase 1: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.
- Phase 1: Maximum Concentration of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1: Time to Maximum Concentration (Tmax) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1: Apparent Terminal Phase Half-life (t½) of AGI-16903 After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
t1/2 was not calculated when the terminal elimination rate constant (λz) was not estimable.
- Phase 1: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of AGI-16903 After Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.
- Phase 1: AUC From Time Zero to 10 Hours Postdose (AUC0-10) of AGI-16903 After Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 10 hours post-dose (AUC0-10) was calculated using the linear trapezoidal rule.
- Phase 1: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) of AGI-16903 After Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.
- Phase 1: Maximum Concentration (Cmax) of AGI-16903 After Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1: Time to Maximum Concentration (Tmax) of AGI-16903 After Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 2 Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 2: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, and 8 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.
- Phase 2: AUC From Time Zero to 24 Hours Postdose (AUC0-24) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.
- Phase 2: AUC From Time Zero to the Last Quantifiable Concentration (AUC0-t) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-t) was calculated using the linear trapezoidal rule.
- Phase 2: Maximum Concentration (Cmax) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 2: Time to Maximum Concentration (Tmax) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 2: Apparent Terminal Phase Half-life (t1/2) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1 Day 1 and Cycle 2 Day 1 at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1 and 2: AUC From Time Zero to 8 Hours Postdose (AUC0-8) After Single and Multiple Oral Doses of Enasidenib 100 mg QD [ Time Frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, and 8 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis.
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.
- Phase 1 and 2: AUC From Time Zero to 24 Hours Postdose (AUC0-24) After Single and Multiple Oral Doses of Enasidenib 100 mg QD [ Time Frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis.
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.
- Phase 1 and 2: Maximum Concentration (Cmax) After Single and Multiple Oral Doses of Enasidenib 100 mg QD [ Time Frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis.
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1 and 2: Time to Maximum Concentration (Tmax) After Single and Multiple Oral Doses of Enasidenib 100 mg QD [ Time Frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis.
Plasma enasidenib was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1 and 2: AUC From Time Zero to 8 Hours Postdose (AUC0-8) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib 100 mg QD [ Time Frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, and 8 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis.
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 8 hours post-dose (AUC0-8) was calculated using the linear trapezoidal rule.
- Phase 1 and 2: AUC From Time Zero to 24 Hours Postdose (AUC0-24) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib 100 mg QD [ Time Frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, and 24 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis.
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) was calculated using the linear trapezoidal rule.
- Phase 1 and 2: Maximum Concentration (Cmax) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib 100 mg QD [ Time Frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis.
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1 and 2: Time to Maximum Concentration (Tmax) of AGI-16903 After Single and Multiple Oral Doses of Enasidenib 100 mg QD [ Time Frame: Day -3 (Phase 1 only) predose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose or Cycle 1 Day 1 (Phase 2) and Cycle 2 Day 1 (Phase 1 & 2) at predose and 2, 4, 6, 8, and 24 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3) for single dose PK analysis, and underwent PK assessments on Cycle 2, Day 1 for multiple dose (steady-state) PK analysis. Participants in Phase 2 underwent PK assessments on Cycle 1, Day 1 for single dose analysis and on Cycle 2, Day 1 for multiple dose (steady-state) analysis.
AGI-16903 is a primary metabolite of enasidenib. Plasma AGI-16903 was measured using validated liquid chromatography-mass spectrometry methods (LC-MS/MS). The lower limit of quantification (LLOQ) in plasma was 1.00 ng/mL.
- Phase 1: Percent Change From Baseline for Area Under the Effect Concentration Time Curve From Time 0 to 10 Hours Postdose (%BAUEC0-10) of 2-hydroxyglutarate (2-HG) on Day -3 [ Time Frame: Screening visit, Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma 2-HG was measured using qualified LC-MS/MS in order to characterize the pharmacodynamic (PD) effects of enasidenib; the LLOQ was 30.0 ng/mL.
Area under the effect concentration time curve from time point zero (predose) up to 10 hours postdose (AUEC0-10) was calculated using the linear trapezoid rule. Percent change from Baseline for AUEC0-10 was calculated as (AUEC0-10 minus [Baseline*Tlast]) / (Baseline*Tlast) * 100, where Tlast corresponded to 10 hours and Baseline was equal to the average of the Screening and Day -3 (predose) 2-HG values.
Data reported are the arithmetic mean and relative standard deviation expressed as a percentage.
- Phase 1: Minimum Percent Change From Baseline Response Value Post-dose Over 10 Hours (%BRmin) for 2-HG After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Screening visit, Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma 2-HG was measured using qualified LC-MS/MS in order to characterize the pharmacodynamic (PD) effects of enasidenib; the LLOQ was 30.0 ng/mL.
Minimum percent change from Baseline response value post-dose over 10 hours was calculated as:
(minimum observed concentration post-dose over 10 hours [Rmin] - Baseline) / Baseline * 100. Baseline was equal to the average of the Screening and Day -3 (predose) 2-HG values.
Data reported are the arithmetic mean and relative standard deviation expressed as a percentage.
- Phase 1: Time of Minimum Observed Concentration Over 72 Hours Postdose (Tmin) of 2-HG After a Single Oral Dose of Enasidenib on Day -3 [ Time Frame: Day -3 prior to the single dose of enasidenib and at 0.5, 1, 2, 3, 4, 6, 8, 10, 24, 48, and 72 hours post-dose. ]
The first 3 participants enrolled in each cohort of the dose escalation phase and the first 15 participants enrolled in each arm of Phase 1 Expansion received a single dose of enasidenib three days prior to starting the 28-day dosing regimen (Day -3).
Plasma 2-HG was measured using qualified LC-MS/MS, the LLOQ was 30.0 ng/mL.
- Phase 1: Percent Change From Baseline for Area Under the Effect Concentration Time Curve From Time 0 to 10 Hours Postdose of 2-HG After Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1, Day 15 and Cycle 2, Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
Plasma 2-HG was measured using qualified LC-MS/MS, the LLOQ was 30.0 ng/mL. Area under the effect concentration time curve from time point zero (predose) up to 10 hours postdose (AUEC0-10) was calculated using the linear trapezoid rule. Percent change from baseline for AUEC0-10 was calculated as:
(AUEC0-10 minus [Baseline*Tlast]) / (Baseline*Tlast) * 100, where Tlast corresponded to 10 hours and Baseline was equal to the average of the Screening and Day -3 (predose) 2-HG values.
Data reported are the arithmetic mean and relative standard deviation expressed as a percentage.
- Phase 1: Minimum Percent Change From Baseline Response Value Post-dose Over 10 Hours (%BRmin) for 2-HG After Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1, Day 15 and Cycle 2, Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
Plasma 2-HG was measured using qualified LC-MS/MS, the LLOQ was 30.0 ng/mL.
Minimum percent change from Baseline response value post-dose over 10 hours was calculated as:
(minimum observed concentration post-dose over 10 hours [Rmin] - Baseline) / Baseline * 100. Baseline was equal to the average of the Screening and Day -3 (predose) 2-HG values.
Data reported are the arithmetic mean and relative standard deviation expressed as a percentage.
- Phase 1: Time of Minimum Observed Concentration Over 10 Hours Postdose (Tmin) of 2-HG After Multiple Oral Doses of Enasidenib [ Time Frame: Cycle 1, Day 15 and Cycle 2, Day 1 at predose and 0.5, 1, 2, 3, 4, 6, 8, and 10 hours post-dose. ]
Plasma 2-HG was measured using qualified LC-MS/MS, the LLOQ was 30.0 ng/mL.
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