Leukemia
Conditions
Keywords
Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Acute, Leukemia, Leukemia
Brief summary
This study is a multicenter, non-randomized, open-label, Phase 2 study of intravenous LY2090314 in participants with acute leukemia.
Interventions
DRUGLY2090314
Administered intravenously
Sponsors
Eli Lilly and Company
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
* Participants must have confirmed diagnosis of one of the following: * Acute myelogenous leukemia (AML) that is refractory or relapsed disease. If participants have acute promyelocytic leukemia (APL), they must have received prior all-trans retinoic acid and arsenic trioxide unless ineligible or intolerant to them * Untreated AML (de novo or arising from a myelodysplastic syndrome). In the opinion of the investigator, the participant should not be a candidate for standard therapy and a clinical trial is a preferred treatment option * Have given written informed consent prior to any study-specific procedures * Have adequate organ function including: * Hepatic: Bilirubin less than or equal to 1.5 times the upper limit of normal (ULN). Alkaline phosphatase (ALP) and transaminases \[alanine aminotransferase (ALT) and aspartate aminotransferase (AST)\] less than or equal to 5 times ULN * Renal: Serum creatinine less than or equal to the ULN. No known active renal disease. In rare cases, participants may enter treatment with a serum creatinine greater than the ULN as elevations of serum creatinine may be secondary to dehydration * Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale * Have discontinued all previous approved therapies for acute leukemia, including chemotherapy for at least 14 days, and recovered from the acute effects of therapy. Hydroxyurea used to control peripheral blast count is permitted within the first 2 cycles of treatment on study, but it must be stopped at least 24 hours before study drug administration in Cycle 3 * Are reliable and willing to be available for the duration of the study and are willing to follow study procedures * Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug * Females with childbearing potential must have had a negative urine or serum pregnancy test less than or equal to 7 days prior to the first dose of study drug * Have an estimated life expectancy of greater than or equal to 6 weeks
Exclusion criteria
* Have received treatment within 14 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication * Participants with chronic myelogenous leukemia (CML) including blast crisis phase * Participants with known central nervous system (CNS) leukemia by spinal fluid cytology or imaging * Have serious pre-existing medical conditions (left to the discretion of the investigator) * Have one of the following abnormalities: QTc (Fridericia corrected) interval \>450 milliseconds (msec) on screening electrocardiogram (ECG), previous history of QTc prolongation with another medication that required discontinuation, congenital long QT syndrome, previous history of ventricular tachycardia or unexplained syncope, left bundle branch block, or chronic atrial fibrillation * Have family history of long QT syndrome or sudden death due to ventricular arrhythmia * Concomitant medication that may cause QTc prolongation or induce Torsades de Pointes at the time of study entry * Have systolic blood pressure greater than or equal to 160 millimeter of mercury (mm Hg) and diastolic blood pressure greater than or equal to 100 mm Hg * Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class II or higher or participants with a history of arrhythmia that is symptomatic or requires treatment * Have uncorrected electrolyte disorders including potassium * Have other active malignancy (with the exception of basal and squamous cell skin cancer) at time of study entry * Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug * Have uncontrolled systemic infection * Females who are pregnant or lactating * Presence of clinical evidence of viral disease caused by human immunodeficiency virus, hepatitis B, or hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)] | Drug-related events were defined as treatment-emergent serious and other non-serious AEs that were considered by the investigator to be related to study drug. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Best Response of Complete Response or Partial Response | Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles) | The Revised International Working Group criteria were used to determine the response for participants with AML. Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as \<5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100\*10\^9/L and ANC ≥1\*10\^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Percentage of participants=\[(number of participants with CR or PR)/(number of participants treated)\]\*100. |
| Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)] | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] | AUC(0-8) was estimated from the plasma drug concentration time profile. |
| PK: AUC From Time 0 to Infinity [AUC(0-inf)] | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] | AUC(0-inf) was estimated from the plasma drug concentration time profile. |
| Number of Participants With Best Response of Complete Response or Partial Response | Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles) | The Revised International Working Group criteria were used to determine the response for participants with acute myelogenous leukemia (AML). Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as \<5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100\*10\^9/Liter (L) and absolute neutrophil count (ANC) ≥1\*10\^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. |
| Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1: D1 and D9 (predose, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion started); Cycle 1: D5, D8, and D12 and C2 through C9: D1 (predose, 2 h after infusion started); Cycle 1: D15 (predose, 1 h, 2 h, 4 h, and 8 h after infusion started) | Percent change=\[(β-catenin level postdose-predose level)/(predose β-catenin levels)\]\*100. Participants in Cohort 1 had β-catenin samples collected on Cycle 1: D1, D8, and D15, and Cycles 2 through 9: D1. Participants in Cohort 2 had β-catenin samples collected on Cycle 1: D1, D5, and D9 and Cycles 2 through 9: D1. Participants in Cohort 3 had β-catenin samples collected on Cycle 1: D1, D5, D9, and D12 and Cycles 2 through 9: D1. |
| Number of Participants Who Died | Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)] | The number of participants who died while on study treatment and the number of participants who died during the 30-day follow-up (30 days post last dose) are reported. |
| PK: Maximum Concentration (Cmax) | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] | Cmax is the maximum observed concentration estimated from the plasma drug concentration time profile. |
Countries
United States
Participant flow
Pre-assignment details
Study had safety lead-in phase \[40 milligrams (mg) LY2090314 administered using 3 treatment schedules\]. Each cohort of participants had different schedule. Safety lead-in data determined if expansion phase opened to enrollment. No participant enrolled in expansion phase. Participants who completed 2 cycles of treatment considered study completers.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles.
If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | 7 |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles.
If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | 6 |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles.
If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | 7 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Progressive Disease | 4 | 1 | 3 |
Baseline characteristics
| Characteristic | Cohort 1, 40 mg LY2090314: D1, D8, D15 | Total | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Cohort 2, 40 mg LY2090314: D1, D5, D9 |
|---|---|---|---|---|
| Age, Continuous | 75.3 years STANDARD_DEVIATION 7.16 | 68.5 years STANDARD_DEVIATION 11.73 | 67.6 years STANDARD_DEVIATION 9.81 | 61.7 years STANDARD_DEVIATION 14.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 20 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 18 Participants | 5 Participants | 6 Participants |
| Region of Enrollment United States | 7 Participants | 20 Participants | 7 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 10 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 10 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 4 / 7 | 5 / 6 | 6 / 7 |
Outcome results
Primary
Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs)
Drug-related events were defined as treatment-emergent serious and other non-serious AEs that were considered by the investigator to be related to study drug. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Study Drug-Related AE(s) | 6 Participants |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Study Drug-Related SAE(s) | 0 Participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Study Drug-Related AE(s) | 5 Participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Study Drug-Related SAE(s) | 2 Participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Study Drug-Related AE(s) | 6 Participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) | Study Drug-Related SAE(s) | 1 Participants |
Secondary
Number of Participants Who Died
The number of participants who died while on study treatment and the number of participants who died during the 30-day follow-up (30 days post last dose) are reported.
Time frame: Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Number of Participants Who Died | Death During 30-Day Follow-Up | 2 Participants |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Number of Participants Who Died | Death On Study, Post Cycle 2 Completion | 0 Participants |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Number of Participants Who Died | Death On Study, Prior To Cycle 2 Completion | 1 Participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Number of Participants Who Died | Death During 30-Day Follow-Up | 1 Participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Number of Participants Who Died | Death On Study, Post Cycle 2 Completion | 1 Participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Number of Participants Who Died | Death On Study, Prior To Cycle 2 Completion | 0 Participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Number of Participants Who Died | Death On Study, Post Cycle 2 Completion | 0 Participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Number of Participants Who Died | Death On Study, Prior To Cycle 2 Completion | 0 Participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Number of Participants Who Died | Death During 30-Day Follow-Up | 0 Participants |
Secondary
Number of Participants With Best Response of Complete Response or Partial Response
The Revised International Working Group criteria were used to determine the response for participants with acute myelogenous leukemia (AML). Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as \<5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100\*10\^9/Liter (L) and absolute neutrophil count (ANC) ≥1\*10\^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
Time frame: Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Number of Participants With Best Response of Complete Response or Partial Response | CR | 0 Participants |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Number of Participants With Best Response of Complete Response or Partial Response | PR | 0 Participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Number of Participants With Best Response of Complete Response or Partial Response | CR | 0 Participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Number of Participants With Best Response of Complete Response or Partial Response | PR | 0 Participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Number of Participants With Best Response of Complete Response or Partial Response | CR | 0 Participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Number of Participants With Best Response of Complete Response or Partial Response | PR | 0 Participants |
Secondary
Percentage of Participants With Best Response of Complete Response or Partial Response
The Revised International Working Group criteria were used to determine the response for participants with AML. Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as \<5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100\*10\^9/L and ANC ≥1\*10\^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Percentage of participants=\[(number of participants with CR or PR)/(number of participants treated)\]\*100.
Time frame: Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)
Population: Participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percentage of Participants With Best Response of Complete Response or Partial Response | PR | 0.0 percentage of participants |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percentage of Participants With Best Response of Complete Response or Partial Response | CR | 0.0 percentage of participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Percentage of Participants With Best Response of Complete Response or Partial Response | CR | 0.0 percentage of participants |
| Cohort 2, 40 mg LY2090314: D1, D5, D9 | Percentage of Participants With Best Response of Complete Response or Partial Response | PR | 0.0 percentage of participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Percentage of Participants With Best Response of Complete Response or Partial Response | CR | 0.0 percentage of participants |
| Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Percentage of Participants With Best Response of Complete Response or Partial Response | PR | 0.0 percentage of participants |
Secondary
Percent Change From Predose Beta (β)-Catenin Levels
Percent change=\[(β-catenin level postdose-predose level)/(predose β-catenin levels)\]\*100. Participants in Cohort 1 had β-catenin samples collected on Cycle 1: D1, D8, and D15, and Cycles 2 through 9: D1. Participants in Cohort 2 had β-catenin samples collected on Cycle 1: D1, D5, and D9 and Cycles 2 through 9: D1. Participants in Cohort 3 had β-catenin samples collected on Cycle 1: D1, D5, D9, and D12 and Cycles 2 through 9: D1.
Time frame: Cycle 1: D1 and D9 (predose, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion started); Cycle 1: D5, D8, and D12 and C2 through C9: D1 (predose, 2 h after infusion started); Cycle 1: D15 (predose, 1 h, 2 h, 4 h, and 8 h after infusion started)
Population: Participants who received at least 1 dose of study drug and had a predose and at least 1 postdose β-catenin sample collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 1, 1 h postdose | 557.4 percent change | Standard Deviation 397.49 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 9, 1 h postdose | 736.1 percent change | Standard Deviation 831.56 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 9, 2 h postdose | 746.5 percent change | Standard Deviation 728.22 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 9, 4 h postdose | 684.3 percent change | Standard Deviation 630.99 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 9, 8 h postdose | 141.2 percent change | Standard Deviation 133.13 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 15, 1 h postdose | 362.3 percent change | Standard Deviation 246.81 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 15, 2 h postdose | 470.6 percent change | Standard Deviation 296.31 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 15, 4 h postdose | 575.5 percent change | Standard Deviation 422.33 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 15, 8 h postdose | 474.2 percent change | Standard Deviation 499.3 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 6, Day 1, 2 h postdose | 80.0 percent change | Standard Deviation 77.57 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 7, Day 1, 2 h postdose | 151.3 percent change | Standard Deviation 155.6 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 8, Day 1, 2 h postdose | 418.6 percent change | Standard Deviation 357.18 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 1, 2 h postdose | 513.7 percent change | Standard Deviation 284.19 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 1, 4 h postdose | 547.6 percent change | Standard Deviation 342.89 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 1, 8 h postdose | 285.7 percent change | Standard Deviation 421.91 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 1, 24 h postdose | 83.6 percent change | Standard Deviation 141.96 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 5, 2 h postdose | 817.2 percent change | Standard Deviation 576.25 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 8, 2 h postdose | 343.2 percent change | Standard Deviation 216.26 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 9, 24 h postdose | 9.1 percent change | Standard Deviation 99.14 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 1, Day 12, 2 h postdose | 837.8 percent change | Standard Deviation 496.95 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 2, Day 1, 2 h postdose | 429.1 percent change | Standard Deviation 339.86 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 3, Day 1, 2 h postdose | 348.5 percent change | Standard Deviation 458.67 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 4, Day 1, 2 h postdose | 408.5 percent change | Standard Deviation 291.78 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 5, Day 1, 2 h postdose | 186.3 percent change | Standard Deviation 188.34 |
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Percent Change From Predose Beta (β)-Catenin Levels | Cycle 9, Day 1, 2 h postdose | 83.1 percent change | — |
Secondary
Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)]
AUC(0-8) was estimated from the plasma drug concentration time profile.
Time frame: Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)]
Population: Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)] | 898 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 47 |
Secondary
PK: AUC From Time 0 to Infinity [AUC(0-inf)]
AUC(0-inf) was estimated from the plasma drug concentration time profile.
Time frame: Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)]
Population: Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | PK: AUC From Time 0 to Infinity [AUC(0-inf)] | 963 ng*h/mL | Geometric Coefficient of Variation 46.4 |
Secondary
PK: Maximum Concentration (Cmax)
Cmax is the maximum observed concentration estimated from the plasma drug concentration time profile.
Time frame: Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)]
Population: Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | PK: Maximum Concentration (Cmax) | 476 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.5 |