Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia, Myelodysplastic Syndromes
Conditions
Keywords
AML, ALL, MDS, CML, Kinase Inhibitor
Brief summary
Non-randomized, open, dose ranging and dose scheduling study of ascending doses of KW-2449 in subjects with AML, ALL, MDS and CML.
Detailed description
This is a Phase I open-label dose escalation study of KW-2449 in subjects with acute leukemias, high risk MDS, and CML who are not candidates for approved therapy. Over an 18-month period, the investigative sites collectively will enroll up to a total of 96 subjects. Subjects will be enrolled sequentially into 1 of 7 dose groups to evaluate 2 dosing schedules (Arm A = 14 consecutive days of dosing followed by a 7-28 day rest period as determined by recovery from any acute hematologic and non-hematologic toxicities, or Arm B = 28 consecutive days of dosing followed by a 7-28 day rest period, as determined by recovery from any acute hematologic and non-hematologic toxicities). The safety of a dose level in Arm A (14-day dosing regimen) will be established prior to enrollment of subjects in the same dose level in Arm B (28-day dosing regimen). In April 2007 the protocol was amended to discontinue Arm B (28 consecutive days of dosing). The protocol will continue as planned for Arm A (14 days of consecutive dosing). Enrollment will proceed until a maximum tolerated dose (MTD) has been established for each study Arm. Once the MTD has been reached, 12 additional subjects, with 1 or more of the hematologic conditions included in this study, may be enrolled at the MTD as an expanded safety cohort.
Interventions
DRUGKW-2449
Sequential ascending oral doses of KW-2449 given for 14 or 28 days (modified by protocol amendment to only 14 days dosing).
Sponsors
Kyowa Kirin, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed diagnosis of: * AML (including APL refractory to all-trans retinoic acid and arsenic) that has relapsed or was not responsive to prior chemotherapy; * Relapsed/refractory ALL; * CML that has failed to respond or has lost a response to imatinib; and * Advanced MDS (INT-2 and High risk by IPSS) with failure or intolerance to approved therapy. 2. ECOG Performance Status score of 0, 1, or 2; 3. Male or female, at least 18 years of age; 4. Signed written informed consent; 5. Serum creatinine ≤ 2.0 mg/dL; 6. Serum SGOT (AST) and SGPT (ALT) ≤ 5x ULN; serum bilirubin ≤ 2 mg/dL (serum bilirubin may be ≤ 3.0 mg/dL in any subject with Gilbert's Syndrome); and 7. For females of childbearing potential, a negative serum pregnancy test. Subjects, of childbearing potential, must use an Investigator-approved method of birth control.
Exclusion criteria
1. Candidates for approved therapies; 2. Concomitant treatment with any investigational agent, chemotherapy, radiotherapy, or immunotherapy; 3. Active CNS leukemia; 4. Previous or concurrent malignancy except noninvasive non-melanomatous skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 2 years prior to study entry; 5. Uncontrolled systemic infection (viral, bacterial, or fungal); 6. Uncontrollable disseminated intravascular coagulation; 7. Major surgery within the 28 days preceding the first dose KW-2449; 8. Radiotherapy, or lack of recovery of any radiotherapy-related acute toxicity, within the 28 days preceding the first dose KW-2449; 9. Treatment with systemic therapy for the underlying hematologic condition, or lack of recovery of toxicity from such treatment, within 28 days of the first dose of KW-2449, with the following exceptions: hydroxyurea for treatment of hyperleukocytosis (discontinued for at least 48 hours prior to the first dose of KW-2449); imatinib (discontinued for at least 48 hours prior to the first dose of KW-2449); and interferon (discontinued for at least 7 days prior to the first dose of KW-2449); 10. Treatment with any other investigational agent, or lack of recovery of toxicity from such treatment, within the 28 days preceding the first dose of KW-2449; 11. Positive serology for HIV; 12. Clinically significant cardiac dysfunction (New York Heart Association Class 3 or 4) at the time of screening, or a history of myocardial infarction or heart failure within 3 months preceding the first dose of KW-2449; 13. Any evidence of chronic Graft versus Host Disease; 14. Active autoimmune disease requiring immunosuppressive therapy; 15. Female subjects who are pregnant or breast feeding; 16. Subjects of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with the institution's standards; 17. Known current drug or alcohol abuse; 18. Other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may compromise the safety of the subject during the study, affect the subject's ability to complete the study, or interfere with interpretation of study results; or 19. For any reason is judged by the Investigator to be inappropriate for study participation, including an inability to communicate or cooperate with the Investigator. 20. Hematopoietic growth factors (i.e., such as erythropoietin or darbepoetin alpha, filgrastim \[granulocyte colony-stimulating factor {G-CSF }\], sargramostim \[granulocyte-macrophage colony-stimulating factor {GM-CSF}\], or other thrombopoietic agents) and corticosteroids within 14 days of study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Baseline up to Cycle 2, Day 1 | In addition to the number of TEAEs, the number of serious TEAEs, the number of related TEAEs, the number of Grade 3-4 TEAEs, and the number of subjects who died or discontinued due to TEAEs were also assessed. The maximally tolerated dose (MTD) was also to be determined, but it was not actually reached in either arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Peak Plasma Concentration (Tmax) | Days 1 and 14 (and Day 28 for Arm B) of Cycle 1 | — |
| Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | Days 1 and 14 (and Day 28 for Arm B) of Cycle 1 | — |
| Observed Peak Plasma Concentration (Cmax) | Days 1 and 14 (and Day 28 for Arm B) of Cycle 1 | — |
| Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | Day 1 and either Day 14 or Day 28 of Cycle 1 | — |
| Disease Response | Day 14 (Arm A) or Day 28 (Arm B) for all cycles | Disease response (i.e., complete or partial remission) based on standard criteria: Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-4649. Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-3674. VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel. Criteria for use of Imatinib Mesylate (Gleevec®) \[updated March 2002; cited 2005 Nov 16\]. Available from: http://www.pbm.va.gov/archive/imatinibcriteria.pdf |
| Terminal Half Life (t 1/2) | Days 1 and 14 (and Day 28 for Arm B) of Cycle 1 | — |
Countries
United States
Participant flow
Recruitment details
Four study centers in the US
Participants by arm
| Arm | Count |
|---|---|
| Arm A: KW-2449 14-day Regimen Sequential ascending oral doses of KW-2449 given for 14-day cycles | 26 |
| Arm B: KW-2449 28-day Regimen Sequential ascending oral doses of KW-2449 given for 28-day cycles | 11 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Not Stated | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 1 |
| Overall Study | Progressive Disease | 2 | 2 | 4 | 3 | 3 | 1 | 2 | 2 | 2 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Switched to alternative treatment | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm B: KW-2449 28-day Regimen | Total | Arm A: KW-2449 14-day Regimen |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 14 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 23 Participants | 18 Participants |
| Age, Continuous | 62.1 years STANDARD_DEVIATION 17.22 | 61.6 years STANDARD_DEVIATION 12 | 61.4 years STANDARD_DEVIATION 15.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 33 Participants | 23 Participants |
| Region of Enrollment United States | 11 participants | 37 participants | 26 participants |
| Sex: Female, Male Female | 6 Participants | 21 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 16 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 3 / 3 | 4 / 4 | 2 / 2 | 5 / 5 | 26 / 26 | 4 / 4 | 4 / 4 | 3 / 3 | 11 / 11 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 5 / 6 | 2 / 3 | 4 / 4 | 1 / 2 | 3 / 5 | 19 / 26 | 2 / 4 | 3 / 4 | 3 / 3 | 8 / 11 |
Outcome results
Primary
Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0
In addition to the number of TEAEs, the number of serious TEAEs, the number of related TEAEs, the number of Grade 3-4 TEAEs, and the number of subjects who died or discontinued due to TEAEs were also assessed. The maximally tolerated dose (MTD) was also to be determined, but it was not actually reached in either arm.
Time frame: Baseline up to Cycle 2, Day 1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 1 participants |
| Arm A - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm A - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 2 participants |
| Arm A - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 3 participants |
| Arm A - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 2 participants |
| Arm A - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 1 participants |
| Arm A - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm A - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 0 participants |
| Arm A - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 3 participants |
| Arm A - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 2 participants |
| Arm A - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 3 participants |
| Arm A - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 2 participants |
| Arm A - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 6 participants |
| Arm A - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 6 participants |
| Arm A - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 5 participants |
| Arm A - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 5 participants |
| Arm A - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm A - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 6 participants |
| Arm A - 200 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 3 participants |
| Arm A - 200 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 2 participants |
| Arm A - 200 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 2 participants |
| Arm A - 200 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 3 participants |
| Arm A - 200 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 1 participants |
| Arm A - 200 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm A - 300 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm A - 300 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 4 participants |
| Arm A - 300 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 4 participants |
| Arm A - 300 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 4 participants |
| Arm A - 300 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 4 participants |
| Arm A - 300 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 3 participants |
| Arm A - 400 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm A - 400 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 2 participants |
| Arm A - 400 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 1 participants |
| Arm A - 400 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 2 participants |
| Arm A - 400 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 2 participants |
| Arm A - 400 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 0 participants |
| Arm A - 500 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 3 participants |
| Arm A - 500 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 3 participants |
| Arm A - 500 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 3 participants |
| Arm A - 500 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm A - 500 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 5 participants |
| Arm A - 500 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 1 participants |
| Arm A - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 26 participants |
| Arm A - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm A - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 11 participants |
| Arm A - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 19 participants |
| Arm A - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 22 participants |
| Arm A - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 21 participants |
| Arm B - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 1 participants |
| Arm B - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 0 participants |
| Arm B - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm B - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 4 participants |
| Arm B - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 2 participants |
| Arm B - 25 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 3 participants |
| Arm B - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm B - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 3 participants |
| Arm B - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 4 participants |
| Arm B - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 3 participants |
| Arm B - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 1 participants |
| Arm B - 50 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 3 participants |
| Arm B - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 3 participants |
| Arm B - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 0 participants |
| Arm B - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 3 participants |
| Arm B - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 3 participants |
| Arm B - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm B - 100 mg/Day | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 3 participants |
| Arm B - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who discontinued the study due to TEA | 0 participants |
| Arm B - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any serious TEAE | 8 participants |
| Arm B - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with any TEAE | 11 participants |
| Arm B - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects who died | 1 participants |
| Arm B - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE of Grade 3 or above | 7 participants |
| Arm B - Total | Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 | Subjects with TEAE related to study drug | 9 participants |
Secondary
Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1)
Time frame: Day 1 and either Day 14 or Day 28 of Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A - 25 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.50 Ratio of hr*ng/mL | — |
| Arm A - 50 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.66 Ratio of hr*ng/mL | Standard Deviation 0.389 |
| Arm A - 100 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.50 Ratio of hr*ng/mL | Standard Deviation 0.459 |
| Arm A - 200 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 3.37 Ratio of hr*ng/mL | Standard Deviation 1.45 |
| Arm A - 300 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.28 Ratio of hr*ng/mL | Standard Deviation 0.0271 |
| Arm A - 400 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.68 Ratio of hr*ng/mL | Standard Deviation 0.654 |
| Arm A - 500 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 0.846 Ratio of hr*ng/mL | — |
| Arm A - Total | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 0.953 Ratio of hr*ng/mL | Standard Deviation 0.181 |
| Arm B - 25 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 0.906 Ratio of hr*ng/mL | Standard Deviation 0.622 |
| Arm B - 50 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.42 Ratio of hr*ng/mL | Standard Deviation 0.331 |
| Arm B - 100 mg/Day | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.44 Ratio of hr*ng/mL | Standard Deviation 0.18 |
| Arm B - Total | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.50 Ratio of hr*ng/mL | Standard Deviation 0.187 |
| Arm A - 500 mg/Day: Day 1 | Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) | 1.60 Ratio of hr*ng/mL | — |
Secondary
Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval))
Time frame: Days 1 and 14 (and Day 28 for Arm B) of Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A - 25 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 23.6 hr*ng/mL | Standard Deviation 8.56 |
| Arm A - 50 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 30.9 hr*ng/mL | — |
| Arm A - 100 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 46.7 hr*ng/mL | Standard Deviation 11.1 |
| Arm A - 200 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 77.9 hr*ng/mL | Standard Deviation 29.7 |
| Arm A - 300 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 138 hr*ng/mL | Standard Deviation 41.8 |
| Arm A - 400 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 162 hr*ng/mL | Standard Deviation 28.7 |
| Arm A - 500 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 173 hr*ng/mL | Standard Deviation 90.5 |
| Arm A - Total | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 647 hr*ng/mL | Standard Deviation 665 |
| Arm B - 25 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 428 hr*ng/mL | Standard Deviation 192 |
| Arm B - 50 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 626 hr*ng/mL | Standard Deviation 310 |
| Arm B - 100 mg/Day | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 647 hr*ng/mL | Standard Deviation 73.5 |
| Arm B - Total | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 1060 hr*ng/mL | Standard Deviation 300 |
| Arm A - 500 mg/Day: Day 1 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 822 hr*ng/mL | Standard Deviation 463 |
| Arm A - 500 mg/Day: Day 14 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 1200 hr*ng/mL | Standard Deviation 180 |
| Arm B - 25 mg/Day: Day 1 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 38.0 hr*ng/mL | Standard Deviation 18 |
| Arm B - 25 mg/Day: Day 14 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 35.3 hr*ng/mL | Standard Deviation 8.76 |
| Arm B - 25 mg/Day: Day 28 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 28.8 hr*ng/mL | Standard Deviation 7.36 |
| Arm B - 50 mg/Day: Day 1 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 36.3 hr*ng/mL | Standard Deviation 18.1 |
| Arm B - 50 mg/Day: Day 14 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 58.7 hr*ng/mL | Standard Deviation 21.7 |
| Arm B - 50 mg/Day: Day 28 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 60.3 hr*ng/mL | Standard Deviation 23.6 |
| Arm B - 100 mg.Day: Day 1 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 107 hr*ng/mL | Standard Deviation 31.2 |
| Arm B - 100 mg/Day: Day 14 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 158 hr*ng/mL | Standard Deviation 58.8 |
| Arm B - 100 mg/Day: Day 28 | Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) | 147 hr*ng/mL | Standard Deviation 90.9 |
Secondary
Disease Response
Disease response (i.e., complete or partial remission) based on standard criteria: Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-4649. Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-3674. VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel. Criteria for use of Imatinib Mesylate (Gleevec®) \[updated March 2002; cited 2005 Nov 16\]. Available from: http://www.pbm.va.gov/archive/imatinibcriteria.pdf
Time frame: Day 14 (Arm A) or Day 28 (Arm B) for all cycles
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A - 25 mg/Day | Disease Response | 0 number of responders |
| Arm A - 50 mg/Day | Disease Response | 0 number of responders |
| Arm A - 100 mg/Day | Disease Response | 0 number of responders |
| Arm A - 200 mg/Day | Disease Response | 0 number of responders |
| Arm A - 300 mg/Day | Disease Response | 0 number of responders |
| Arm A - 400 mg/Day | Disease Response | 0 number of responders |
| Arm A - 500 mg/Day | Disease Response | 0 number of responders |
| Arm A - Total | Disease Response | 0 number of responders |
| Arm B - 25 mg/Day | Disease Response | 0 number of responders |
| Arm B - 50 mg/Day | Disease Response | 0 number of responders |
| Arm B - 100 mg/Day | Disease Response | 0 number of responders |
| Arm B - Total | Disease Response | 0 number of responders |
Secondary
Observed Peak Plasma Concentration (Cmax)
Time frame: Days 1 and 14 (and Day 28 for Arm B) of Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A - 25 mg/Day | Observed Peak Plasma Concentration (Cmax) | 6.35 ng/mL | Standard Deviation 0.754 |
| Arm A - 50 mg/Day | Observed Peak Plasma Concentration (Cmax) | 7.94 ng/mL | Standard Deviation 3.06 |
| Arm A - 100 mg/Day | Observed Peak Plasma Concentration (Cmax) | 10.5 ng/mL | Standard Deviation 3.49 |
| Arm A - 200 mg/Day | Observed Peak Plasma Concentration (Cmax) | 18.6 ng/mL | Standard Deviation 3.1 |
| Arm A - 300 mg/Day | Observed Peak Plasma Concentration (Cmax) | 34.4 ng/mL | Standard Deviation 15.7 |
| Arm A - 400 mg/Day | Observed Peak Plasma Concentration (Cmax) | 38.8 ng/mL | Standard Deviation 16.1 |
| Arm A - 500 mg/Day | Observed Peak Plasma Concentration (Cmax) | 31.3 ng/mL | Standard Deviation 17.8 |
| Arm A - Total | Observed Peak Plasma Concentration (Cmax) | 83.7 ng/mL | Standard Deviation 97.4 |
| Arm B - 25 mg/Day | Observed Peak Plasma Concentration (Cmax) | 97.5 ng/mL | Standard Deviation 18.6 |
| Arm B - 50 mg/Day | Observed Peak Plasma Concentration (Cmax) | 147 ng/mL | Standard Deviation 77.1 |
| Arm B - 100 mg/Day | Observed Peak Plasma Concentration (Cmax) | 151 ng/mL | Standard Deviation 52.3 |
| Arm B - Total | Observed Peak Plasma Concentration (Cmax) | 198 ng/mL | Standard Deviation 23.3 |
| Arm A - 500 mg/Day: Day 1 | Observed Peak Plasma Concentration (Cmax) | 180 ng/mL | Standard Deviation 125 |
| Arm A - 500 mg/Day: Day 14 | Observed Peak Plasma Concentration (Cmax) | 371 ng/mL | Standard Deviation 129 |
| Arm B - 25 mg/Day: Day 1 | Observed Peak Plasma Concentration (Cmax) | 7.05 ng/mL | Standard Deviation 4.85 |
| Arm B - 25 mg/Day: Day 14 | Observed Peak Plasma Concentration (Cmax) | 8.39 ng/mL | Standard Deviation 1.7 |
| Arm B - 25 mg/Day: Day 28 | Observed Peak Plasma Concentration (Cmax) | 4.49 ng/mL | Standard Deviation 1.97 |
| Arm B - 50 mg/Day: Day 1 | Observed Peak Plasma Concentration (Cmax) | 8.20 ng/mL | Standard Deviation 4.11 |
| Arm B - 50 mg/Day: Day 14 | Observed Peak Plasma Concentration (Cmax) | 12.7 ng/mL | Standard Deviation 4.73 |
| Arm B - 50 mg/Day: Day 28 | Observed Peak Plasma Concentration (Cmax) | 15.6 ng/mL | Standard Deviation 9.43 |
| Arm B - 100 mg.Day: Day 1 | Observed Peak Plasma Concentration (Cmax) | 20.9 ng/mL | Standard Deviation 9.66 |
| Arm B - 100 mg/Day: Day 14 | Observed Peak Plasma Concentration (Cmax) | 36.3 ng/mL | Standard Deviation 15.1 |
| Arm B - 100 mg/Day: Day 28 | Observed Peak Plasma Concentration (Cmax) | 32.5 ng/mL | Standard Deviation 24.6 |
Secondary
Terminal Half Life (t 1/2)
Time frame: Days 1 and 14 (and Day 28 for Arm B) of Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A - 25 mg/Day | Terminal Half Life (t 1/2) | 2.96 hours | Standard Deviation 1.42 |
| Arm A - 50 mg/Day | Terminal Half Life (t 1/2) | 3.36 hours | — |
| Arm A - 100 mg/Day | Terminal Half Life (t 1/2) | 2.67 hours | Standard Deviation 0.435 |
| Arm A - 200 mg/Day | Terminal Half Life (t 1/2) | 3.26 hours | Standard Deviation 0.631 |
| Arm A - 300 mg/Day | Terminal Half Life (t 1/2) | 3.11 hours | Standard Deviation 0.31 |
| Arm A - 400 mg/Day | Terminal Half Life (t 1/2) | 2.80 hours | Standard Deviation 0.187 |
| Arm A - 500 mg/Day | Terminal Half Life (t 1/2) | 3.27 hours | — |
| Arm A - Total | Terminal Half Life (t 1/2) | 3.04 hours | Standard Deviation 0.715 |
| Arm B - 25 mg/Day | Terminal Half Life (t 1/2) | 2.48 hours | Standard Deviation 0.158 |
| Arm B - 50 mg/Day | Terminal Half Life (t 1/2) | 2.44 hours | Standard Deviation 0.149 |
| Arm B - 100 mg/Day | Terminal Half Life (t 1/2) | 2.42 hours | Standard Deviation 0.06 |
| Arm B - Total | Terminal Half Life (t 1/2) | 2.83 hours | Standard Deviation 0.0806 |
| Arm A - 500 mg/Day: Day 1 | Terminal Half Life (t 1/2) | 2.93 hours | Standard Deviation 1.01 |
| Arm A - 500 mg/Day: Day 14 | Terminal Half Life (t 1/2) | 2.47 hours | Standard Deviation 0.105 |
| Arm B - 25 mg/Day: Day 1 | Terminal Half Life (t 1/2) | 2.78 hours | Standard Deviation 0.108 |
| Arm B - 25 mg/Day: Day 14 | Terminal Half Life (t 1/2) | 3.00 hours | Standard Deviation 0.453 |
| Arm B - 25 mg/Day: Day 28 | Terminal Half Life (t 1/2) | 3.35 hours | Standard Deviation 0.443 |
| Arm B - 50 mg/Day: Day 1 | Terminal Half Life (t 1/2) | 3.90 hours | Standard Deviation 1.43 |
| Arm B - 50 mg/Day: Day 14 | Terminal Half Life (t 1/2) | 3.32 hours | Standard Deviation 0.383 |
| Arm B - 50 mg/Day: Day 28 | Terminal Half Life (t 1/2) | 3.88 hours | Standard Deviation 1.64 |
| Arm B - 100 mg.Day: Day 1 | Terminal Half Life (t 1/2) | 2.97 hours | Standard Deviation 0.471 |
| Arm B - 100 mg/Day: Day 14 | Terminal Half Life (t 1/2) | 3.90 hours | Standard Deviation 1.62 |
| Arm B - 100 mg/Day: Day 28 | Terminal Half Life (t 1/2) | 3.16 hours | — |
Secondary
Time to Peak Plasma Concentration (Tmax)
Time frame: Days 1 and 14 (and Day 28 for Arm B) of Cycle 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm A - 25 mg/Day | Time to Peak Plasma Concentration (Tmax) | 1.51 hours | Standard Deviation 0.508 |
| Arm A - 50 mg/Day | Time to Peak Plasma Concentration (Tmax) | 1.83 hours | Standard Deviation 1.18 |
| Arm A - 100 mg/Day | Time to Peak Plasma Concentration (Tmax) | 1.67 hours | Standard Deviation 0.577 |
| Arm A - 200 mg/Day | Time to Peak Plasma Concentration (Tmax) | 2.06 hours | Standard Deviation 0.0962 |
| Arm A - 300 mg/Day | Time to Peak Plasma Concentration (Tmax) | 1.31 hours | Standard Deviation 0.386 |
| Arm A - 400 mg/Day | Time to Peak Plasma Concentration (Tmax) | 0.979 hours | Standard Deviation 0.728 |
| Arm A - 500 mg/Day | Time to Peak Plasma Concentration (Tmax) | 2.97 hours | Standard Deviation 1.71 |
| Arm A - Total | Time to Peak Plasma Concentration (Tmax) | 2.68 hours | Standard Deviation 1.36 |
| Arm B - 25 mg/Day | Time to Peak Plasma Concentration (Tmax) | 1.67 hours | Standard Deviation 0.577 |
| Arm B - 50 mg/Day | Time to Peak Plasma Concentration (Tmax) | 1.50 hours | Standard Deviation 0.707 |
| Arm B - 100 mg/Day | Time to Peak Plasma Concentration (Tmax) | 2.00 hours | Standard Deviation 0 |
| Arm B - Total | Time to Peak Plasma Concentration (Tmax) | 1.57 hours | Standard Deviation 0.613 |
| Arm A - 500 mg/Day: Day 1 | Time to Peak Plasma Concentration (Tmax) | 2.27 hours | Standard Deviation 1.23 |
| Arm A - 500 mg/Day: Day 14 | Time to Peak Plasma Concentration (Tmax) | 1.50 hours | Standard Deviation 0.707 |
| Arm B - 25 mg/Day: Day 1 | Time to Peak Plasma Concentration (Tmax) | 2.27 hours | Standard Deviation 1.28 |
| Arm B - 25 mg/Day: Day 14 | Time to Peak Plasma Concentration (Tmax) | 1.14 hours | Standard Deviation 0.177 |
| Arm B - 25 mg/Day: Day 28 | Time to Peak Plasma Concentration (Tmax) | 1.33 hours | Standard Deviation 0.583 |
| Arm B - 50 mg/Day: Day 1 | Time to Peak Plasma Concentration (Tmax) | 1.26 hours | Standard Deviation 0.506 |
| Arm B - 50 mg/Day: Day 14 | Time to Peak Plasma Concentration (Tmax) | 1.26 hours | Standard Deviation 0.492 |
| Arm B - 50 mg/Day: Day 28 | Time to Peak Plasma Concentration (Tmax) | 1.44 hours | Standard Deviation 0.509 |
| Arm B - 100 mg.Day: Day 1 | Time to Peak Plasma Concentration (Tmax) | 1.34 hours | Standard Deviation 0.587 |
| Arm B - 100 mg/Day: Day 14 | Time to Peak Plasma Concentration (Tmax) | 2.00 hours | Standard Deviation 1.73 |
| Arm B - 100 mg/Day: Day 28 | Time to Peak Plasma Concentration (Tmax) | 1.54 hours | Standard Deviation 0.766 |