Acute Myeloid Leukemia
Conditions
Brief summary
To evaluate the tolerability and pharmacokinetics of SGI-110 when administered subcutaneously to Japanese patients with acute myeloid leukemia (AML).
Interventions
DRUGSGI-110
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female patients with a diagnosis of AML (WHO classification 2008). * Patients, 20 years of age or older, who are unresponsive to standard chemotherapy or have relapsed following standard chemotherapy * Patients, 65 years of age or older, who are not eligible for standard intensive chemotherapy * Patients with ECOG performance status (PS) of 0 to 2 * Patients with adequate organ function * Women of child-bearing potential must not be pregnant or breast feeding (pregnancy test will be performed at Screening). Women of child bearing potential and all men with female partners of child bearing potential must practice two medically acceptable methods of birth control and must not become pregnant or father a child while receiving treatment with SGI-110 and for 3 months following last dosing. * Patients who have undergone prior allogeneic hematopoietic stem cell transplantation must have no evidence of active graft-versus host disease (GVHD) and must be off immunosuppressive therapy by ≥2 weeks prior to IMP administration.
Exclusion criteria
* Patients with acute promyelocytic leukemia accompanied by t(15;17)(q22;q12) or (PML/RARA) karyotype abnormalities (include other variant types of APL) * Patients with multiple cancers (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 3 years) * Subjects with life-threatening illnesses other than AML or MDS, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at risk. * Patients with poorly controlled arrhythmias, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification * Patients with symptomatic central nervous system involvement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | 28 days (Day 1 to Day 29) | DLT was defined as any of the following adverse events (AEs) occurring during Course 1 for which there was a reasonable probability or possibility of a causal relationship with the IMP. The severity of AEs was graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. * Nonhematologic toxicity of Grade ≥3, except for (i) nausea, vomiting, or diarrhea of Grade 3 that is controllable by optimal therapy, and (ii) Grade 3 laboratory findings other than serum creatinine, bilirubin, aspartate aminotransferase, or alanine aminotransferase. * Grade 4 thrombocytopenia that was not present at trial entry and that is not resolved within 7 days * Grade 4 neutropenia that was not present at trial entry and that is not resolved within 7 days * Febrile neutropenia (defined as a neutrophil count of \<500/μL accompanied by a fever of ≥38°C) * Any AE that results in a delay of \>4 weeks in starting the next treatment course |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12) |
| Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12) |
| Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12) |
| Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12) |
Countries
Japan
Participant flow
Pre-assignment details
This trial consisted of a screening period, dose limiting toxicity (DLT) evaluation period (Course 1), and withdrawal examination. Subjects who completed investigational medicinal product (IMP) administration and all observations during the DLT evaluation period, and who did not have any apparent progression of AML, were permitted to be added extended treatment period (Course 2) to continue treatment with IMP following the DLT evaluation period if they wished.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 SGI-110 36mg/m2 was administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28). | 4 |
| Cohort 2 SGI-110 60mg/m2 was administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28). | 6 |
| Cohort 3 SGI-110 60mg/m2 was administered subcutaneously once daily for 10 days in total (Day 1 to Day 5 and Day 8 to Day 12 with dosing, Day 6 and 7 with non-dosing), followed by a 16-day non-dosing period (Day 13 to Day 28). | 7 |
| Cohort 4 SGI-110 90mg/m2 was administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28). | 4 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Course 1 (DLT Evaluation Period) | Clear progression of the primary disease including relapses | 1 | 0 | 0 | 1 |
| Course ≥2 (Extended Treatment Period) | Clear progression of the primary disease including relapses | 2 | 2 | 3 | 1 |
| Course ≥2 (Extended Treatment Period) | Delay in commencement of the next course by more than 4 weeks | 0 | 1 | 0 | 0 |
| Course ≥2 (Extended Treatment Period) | Physician Decision | 0 | 2 | 1 | 0 |
| Course ≥2 (Extended Treatment Period) | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 6 Participants | 7 Participants | 4 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Japanese | 4 Participants | 6 Participants | 7 Participants | 4 Participants | 21 Participants |
| Region of Enrollment Japan | 4 Participants | 6 Participants | 7 Participants | 4 Participants | 21 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 5 Participants | 1 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 6 | 0 / 7 | 0 / 4 |
| other Total, other adverse events | 4 / 4 | 6 / 6 | 7 / 7 | 4 / 4 |
| serious Total, serious adverse events | 2 / 4 | 5 / 6 | 4 / 7 | 1 / 4 |
Outcome results
Primary
Dose Limiting Toxicity (DLT)
DLT was defined as any of the following adverse events (AEs) occurring during Course 1 for which there was a reasonable probability or possibility of a causal relationship with the IMP. The severity of AEs was graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. * Nonhematologic toxicity of Grade ≥3, except for (i) nausea, vomiting, or diarrhea of Grade 3 that is controllable by optimal therapy, and (ii) Grade 3 laboratory findings other than serum creatinine, bilirubin, aspartate aminotransferase, or alanine aminotransferase. * Grade 4 thrombocytopenia that was not present at trial entry and that is not resolved within 7 days * Grade 4 neutropenia that was not present at trial entry and that is not resolved within 7 days * Febrile neutropenia (defined as a neutrophil count of \<500/μL accompanied by a fever of ≥38°C) * Any AE that results in a delay of \>4 weeks in starting the next treatment course
Time frame: 28 days (Day 1 to Day 29)
Population: DLT analysis population included subjects in whom tolerability had been assessed in Cohorts 1 to 4 (subjects who had received all doses and completed all assessments scheduled for the DLT evaluation period).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Dose Limiting Toxicity (DLT) | 0 participants |
| Cohort 2 | Dose Limiting Toxicity (DLT) | 0 participants |
| Cohort 3 | Dose Limiting Toxicity (DLT) | 1 participants |
| Cohort 4 | Dose Limiting Toxicity (DLT) | 0 participants |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time frame: Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12)
Population: Analysis population included subjects whose plasma drug concentrations had been measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 207 ng·h/mL | Standard Deviation 36.1 |
| Cohort 1 | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 70.0 ng·h/mL | Standard Deviation 13.4 |
| Cohort 2 | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 398 ng·h/mL | Standard Deviation 75.7 |
| Cohort 2 | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 151 ng·h/mL | Standard Deviation 42.7 |
| Cohort 3 | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 332 ng·h/mL | Standard Deviation 61.5 |
| Cohort 3 | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 95.7 ng·h/mL | Standard Deviation 11.7 |
| Cohort 4 | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 710 ng·h/mL | Standard Deviation 119 |
| Cohort 4 | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 248 ng·h/mL | Standard Deviation 39.9 |
| Cohort 1 (Day 5) | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 206 ng·h/mL | Standard Deviation 11.7 |
| Cohort 1 (Day 5) | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 67.0 ng·h/mL | Standard Deviation 18.6 |
| Cohort 2 (Day 5) | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 410 ng·h/mL | Standard Deviation 57.9 |
| Cohort 2 (Day 5) | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 150 ng·h/mL | Standard Deviation 34.1 |
| Cohort 3 (Day 12) | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 101 ng·h/mL | Standard Deviation 10.7 |
| Cohort 3 (Day 12) | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 311 ng·h/mL | Standard Deviation 87.2 |
| Cohort 4 (Day 5) | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 581 ng·h/mL | Standard Deviation 124 |
| Cohort 4 (Day 5) | Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 240 ng·h/mL | Standard Deviation 41.6 |
Secondary
Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time frame: Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12)
Population: Analysis population included subjects whose plasma drug concentrations had been measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 96.8 ng/mL | Standard Deviation 37.3 |
| Cohort 1 | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 28.6 ng/mL | Standard Deviation 13.8 |
| Cohort 2 | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 182 ng/mL | Standard Deviation 59.7 |
| Cohort 2 | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 54.1 ng/mL | Standard Deviation 14.7 |
| Cohort 3 | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 140 ng/mL | Standard Deviation 33.1 |
| Cohort 3 | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 31.8 ng/mL | Standard Deviation 4.08 |
| Cohort 4 | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 359 ng/mL | Standard Deviation 220 |
| Cohort 4 | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 109 ng/mL | Standard Deviation 50.3 |
| Cohort 1 (Day 5) | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 142 ng/mL | Standard Deviation 97.4 |
| Cohort 1 (Day 5) | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 38.2 ng/mL | Standard Deviation 34.1 |
| Cohort 2 (Day 5) | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 200 ng/mL | Standard Deviation 42.4 |
| Cohort 2 (Day 5) | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 67.2 ng/mL | Standard Deviation 13.5 |
| Cohort 3 (Day 12) | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 44.5 ng/mL | Standard Deviation 15.3 |
| Cohort 3 (Day 12) | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 155 ng/mL | Standard Deviation 58.5 |
| Cohort 4 (Day 5) | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 328 ng/mL | Standard Deviation 208 |
| Cohort 4 (Day 5) | Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 95.7 ng/mL | Standard Deviation 37.2 |
Secondary
Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time frame: Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12)
Population: Analysis population included subjects whose plasma drug concentrations had been measured.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.698 h | Standard Deviation 0.393 |
| Cohort 1 | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.04 h | Standard Deviation 0.467 |
| Cohort 2 | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.833 h | Standard Deviation 0.493 |
| Cohort 2 | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.12 h | Standard Deviation 0.564 |
| Cohort 3 | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.740 h | Standard Deviation 0.212 |
| Cohort 3 | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.09 h | Standard Deviation 0.148 |
| Cohort 4 | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.656 h | Standard Deviation 0.155 |
| Cohort 4 | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 0.891 h | Standard Deviation 0.099 |
| Cohort 1 (Day 5) | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.599 h | Standard Deviation 0.332 |
| Cohort 1 (Day 5) | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 0.905 h | Standard Deviation 0.385 |
| Cohort 2 (Day 5) | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.503 h | Standard Deviation 0.144 |
| Cohort 2 (Day 5) | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 0.821 h | Standard Deviation 0.231 |
| Cohort 3 (Day 12) | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.14 h | Standard Deviation 0.486 |
| Cohort 3 (Day 12) | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.685 h | Standard Deviation 0.341 |
| Cohort 4 (Day 5) | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.623 h | Standard Deviation 0.153 |
| Cohort 4 (Day 5) | Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 0.875 h | Standard Deviation 0.107 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time frame: Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12)
Population: Analysis population included subjects whose plasma drug concentrations had been measured.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 1.49 h |
| Cohort 1 | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 2.04 h |
| Cohort 2 | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.98 h |
| Cohort 2 | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.27 h |
| Cohort 3 | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 1.48 h |
| Cohort 3 | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.93 h |
| Cohort 4 | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 1.51 h |
| Cohort 4 | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.51 h |
| Cohort 1 (Day 5) | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.99 h |
| Cohort 1 (Day 5) | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.49 h |
| Cohort 2 (Day 5) | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 0.97 h |
| Cohort 2 (Day 5) | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.47 h |
| Cohort 3 (Day 12) | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.43 h |
| Cohort 3 (Day 12) | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 1.42 h |
| Cohort 4 (Day 5) | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | SGI-110 | 1.27 h |
| Cohort 4 (Day 5) | Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110 | decitabine | 1.53 h |