Advanced Cancer
Conditions
Keywords
Advanced cancer
Brief summary
The main purpose of this trial is to determine a recommended Phase 2 dose of LY2584702 that may be safely administered to participants with advanced/metastatic cancer.
Interventions
DRUGLY2584702
administered orally
Sponsors
Eli Lilly and Company
Study design
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histological or cytological evidence of a diagnosis of advanced and/or metastatic cancer (solid tumors) that is refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists * Have the presence of disease amenable to efficacy assessment as defined by the Response Evaluation Criteria in Solid Tumors. Participants who have advanced non-measurable disease with elevation of a validated tumor marker may be eligible, if discussed and agreed upon by the investigator and the sponsor * Participants entering Part C of the study must have a tumor that is safely amenable to 2 biopsies (one pre-treatment and one on-treatment biopsy for the same tumor). Participants in Part C of the study must agree to biopsy procedures at time of consent * Have adequate hematologic, renal, and hepatic organ function * Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy (with the exception of continuing gonadotropic releasing hormone (GnRH) agonist therapy for participants with prostate cancer, or anti-estrogen therapy \[for example, an aromatase inhibitor\] for participants with breast cancer), or other investigational therapy for at least 3 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy * 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 child bearing potential must have had a negative 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 12 weeks * Are able to swallow capsules
Exclusion criteria
* Have received treatment within 3 weeks of the initial dose of study drug with a drug that has not received regulatory approval for any indication * Have 1 or more serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study. * Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastasis is not required * Have hematologic malignancies, or lymphoma * Females who are pregnant or lactating * Have a second primary malignancy that, in the judgement of the investigator and sponsor, may affect the interpretation of results * Have bleeding diathesis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD) | Parts A and B, Baseline through Cycle 1 (1 cycle=28 days) | Based on the maximum tolerated dose (MTD): highest dose where \<33% participants experienced a dose-limiting toxicity (DLT). DLTs were adverse events (AEs) during Cycle 1 that met any 1 of the following criteria using National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE) grading: any ≥Grade 3 nonhematological toxicity (except nausea/vomiting, diarrhea or hypophosphatemia without maximal symptomatic/prophylactic treatment) that was not related to study disease, any ≥Grade 3 thrombocytopenia with bleeding, any Grade 4 hematological toxicity of \>5 days duration or any febrile neutropenia. Investigators, together with the sponsor, could declare a DLT during Cycle 1 if a participant experienced increasing toxicity and it was clear that further treatment would expose the participant to excessive risk. The MTD was below the level required for efficacy, therefore, the study was terminated early and the recommended Phase 2 dose was not calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, 8 hours postdose) | Cmax results on Day 1 and on Day 8 (steady state) are reported. |
| Number of Participants With Tumor Response | Parts A and B, Baseline through study completion [up to Cycle 10 (1 cycle=28 days)] | Tumor response was defined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria. Complete Response (CR) was the disappearance of all target and non-target lesions and normalization of tumor marker levels of non-target lesions; Partial Response (PR) was at least a 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) was at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions; Stable Disease (SD) was small changes that did not meet above criteria including persistence of 1 or more non-target lesion(s). |
| Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | Part A, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose) | Results for AUC from time 0 to infinity \[AUC(0-inf)\] and AUC from time 0 to 24 hours \[AUC(0-24)\] on Day 1 and Day 8 (steady state) are reported for participants on a QD LY2584702 dosing regimen. |
| Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose) | Results for AUC from time 0 to infinity \[AUC(0-inf)\] and AUC from time 0 to 12 hours \[AUC(0-12)\] on Day 1 and Day 8 (steady state) are reported for participants with a BID LY2584702 dosing regimen. |
Countries
United States
Participant flow
Pre-assignment details
Parts A and B of the study were conducted to determine the dose and dosing schedule to be used in Part C (dose confirmation phase). The decision to initiate Part B was based on the safety, pharmacokinetic, and pharmacodynamic results in Part A. The study was terminated prior to participant enrollment in Part C of the study.
Participants by arm
| Arm | Count |
|---|---|
| 25 mg LY2584702 QD Participants received 25 milligrams (mg) of LY2584702 orally as a capsule, once daily (QD) for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | 3 |
| 50 mg LY2584702 QD Participants received 50 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | 8 |
| 100 mg LY2584702 QD Participants received 100 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | 3 |
| 200 mg LY2584702 QD Participants received 200 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | 6 |
| 50 mg LY2584702 BID Participants received 50 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | 3 |
| 75 mg LY2584702 BID Participants received 75 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | 3 |
| 100 mg LY2584702 BID Participants received 100 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | 6 |
| 300 mg LY2584702 BID Participants received 300 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | 2 |
| Total | 34 |
Baseline characteristics
| Characteristic | 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 15.39 | 61.0 years STANDARD_DEVIATION 8.65 | 66.0 years STANDARD_DEVIATION 4.58 | 62.7 years STANDARD_DEVIATION 15.4 | 59.7 years STANDARD_DEVIATION 16.65 | 69.3 years STANDARD_DEVIATION 3.79 | 60.7 years STANDARD_DEVIATION 9.14 | 40.5 years STANDARD_DEVIATION 20.51 | 61.5 years STANDARD_DEVIATION 12.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 7 Participants | 3 Participants | 6 Participants | 3 Participants | 2 Participants | 5 Participants | 1 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 8 Participants | 2 Participants | 6 Participants | 3 Participants | 2 Participants | 5 Participants | 2 Participants | 31 Participants |
| Region of Enrollment United States | 3 Participants | 8 Participants | 3 Participants | 6 Participants | 3 Participants | 3 Participants | 6 Participants | 2 Participants | 34 Participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 5 Participants | 2 Participants | 21 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 13 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 7 / 8 | 2 / 3 | 5 / 6 | 3 / 3 | 3 / 3 | 6 / 6 | 2 / 2 |
| serious Total, serious adverse events | 2 / 3 | 2 / 8 | 1 / 3 | 2 / 6 | 1 / 3 | 1 / 3 | 3 / 6 | 1 / 2 |
Outcome results
Primary
Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD)
Based on the maximum tolerated dose (MTD): highest dose where \<33% participants experienced a dose-limiting toxicity (DLT). DLTs were adverse events (AEs) during Cycle 1 that met any 1 of the following criteria using National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE) grading: any ≥Grade 3 nonhematological toxicity (except nausea/vomiting, diarrhea or hypophosphatemia without maximal symptomatic/prophylactic treatment) that was not related to study disease, any ≥Grade 3 thrombocytopenia with bleeding, any Grade 4 hematological toxicity of \>5 days duration or any febrile neutropenia. Investigators, together with the sponsor, could declare a DLT during Cycle 1 if a participant experienced increasing toxicity and it was clear that further treatment would expose the participant to excessive risk. The MTD was below the level required for efficacy, therefore, the study was terminated early and the recommended Phase 2 dose was not calculated.
Time frame: Parts A and B, Baseline through Cycle 1 (1 cycle=28 days)
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A | Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD) | NA milligrams (mg) |
| Part B | Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD) | NA milligrams (mg) |
Secondary
Number of Participants With Tumor Response
Tumor response was defined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria. Complete Response (CR) was the disappearance of all target and non-target lesions and normalization of tumor marker levels of non-target lesions; Partial Response (PR) was at least a 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) was at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions; Stable Disease (SD) was small changes that did not meet above criteria including persistence of 1 or more non-target lesion(s).
Time frame: Parts A and B, Baseline through study completion [up to Cycle 10 (1 cycle=28 days)]
Population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| Part A | Number of Participants With Tumor Response | Progressive Disease | 2 Participants |
| Part A | Number of Participants With Tumor Response | Stable Disease | 0 Participants |
| Part A | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| Part B | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| Part B | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| Part B | Number of Participants With Tumor Response | Stable Disease | 2 Participants |
| Part B | Number of Participants With Tumor Response | Progressive Disease | 2 Participants |
| 100 mg LY2584702 QD | Number of Participants With Tumor Response | Progressive Disease | 2 Participants |
| 100 mg LY2584702 QD | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 100 mg LY2584702 QD | Number of Participants With Tumor Response | Stable Disease | 0 Participants |
| 100 mg LY2584702 QD | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| 200 mg LY2584702 QD | Number of Participants With Tumor Response | Progressive Disease | 4 Participants |
| 200 mg LY2584702 QD | Number of Participants With Tumor Response | Stable Disease | 0 Participants |
| 200 mg LY2584702 QD | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| 200 mg LY2584702 QD | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 50 mg LY2584702 BID | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 50 mg LY2584702 BID | Number of Participants With Tumor Response | Progressive Disease | 2 Participants |
| 50 mg LY2584702 BID | Number of Participants With Tumor Response | Stable Disease | 1 Participants |
| 50 mg LY2584702 BID | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| 75 mg LY2584702 BID | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| 75 mg LY2584702 BID | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 75 mg LY2584702 BID | Number of Participants With Tumor Response | Stable Disease | 2 Participants |
| 75 mg LY2584702 BID | Number of Participants With Tumor Response | Progressive Disease | 1 Participants |
| 100 mg LY2584702 BID | Number of Participants With Tumor Response | Progressive Disease | 1 Participants |
| 100 mg LY2584702 BID | Number of Participants With Tumor Response | Partial Response | 0 Participants |
| 100 mg LY2584702 BID | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 100 mg LY2584702 BID | Number of Participants With Tumor Response | Stable Disease | 0 Participants |
| 300 mg LY2584702 BID | Number of Participants With Tumor Response | Stable Disease | 0 Participants |
| 300 mg LY2584702 BID | Number of Participants With Tumor Response | Progressive Disease | 0 Participants |
| 300 mg LY2584702 BID | Number of Participants With Tumor Response | Complete Response | 0 Participants |
| 300 mg LY2584702 BID | Number of Participants With Tumor Response | Partial Response | 0 Participants |
Secondary
Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing
Results for AUC from time 0 to infinity \[AUC(0-inf)\] and AUC from time 0 to 24 hours \[AUC(0-24)\] on Day 1 and Day 8 (steady state) are reported for participants on a QD LY2584702 dosing regimen.
Time frame: Part A, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose)
Population: All participants who received at least 1 dose of study drug \[QD dosing regimen (Part A)\].
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-inf), Day 1 | 4831.85 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 59.3 |
| Part A | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-24), Day 8 | 2310.93 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 36.5 |
| Part A | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-24), Day 1 | 3918.51 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 44 |
| Part B | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-inf), Day 1 | 7968.44 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 41.8 |
| Part B | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-24), Day 8 | 5432.02 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 85.1 |
| Part B | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-24), Day 1 | 7505.27 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| 100 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-24), Day 1 | 3885.40 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 18.8 |
| 100 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-inf), Day 1 | 4698.94 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 7.5 |
| 100 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-24), Day 8 | 6106.05 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 57.9 |
| 200 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-inf), Day 1 | 20147.91 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 56.9 |
| 200 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-24), Day 8 | 8731.94 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 78.5 |
| 200 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing | AUC(0-24), Day 1 | 14206.13 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 60.9 |
Secondary
Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing
Results for AUC from time 0 to infinity \[AUC(0-inf)\] and AUC from time 0 to 12 hours \[AUC(0-12)\] on Day 1 and Day 8 (steady state) are reported for participants with a BID LY2584702 dosing regimen.
Time frame: Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose)
Population: All participants who received at least 1 dose of study drug \[BID dosing regimen (Part A or B)\] and had evaluable AUC data. In 300 mg LY2584702 BID group data was not analyzed for AUC(0-12) day 8 due to insufficient participants at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-12), Day 8 | 4470.57 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 39.4 |
| Part A | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-inf), Day 1 | 3922.09 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 70 |
| Part A | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-12), Day 1 | 2461.26 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 83.9 |
| Part B | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-inf), Day 1 | 12381.00 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 70 |
| Part B | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-12), Day 8 | 6669.70 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 46.3 |
| Part B | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-12), Day 1 | 6389.44 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 57.5 |
| 100 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-12), Day 8 | 13718.79 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 53.3 |
| 100 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-inf), Day 1 | 11625.53 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 59.3 |
| 100 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-12), Day 1 | 6856.58 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 53.4 |
| 200 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-12), Day 1 | 13084.5 nanograms*hours/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 90.5 |
| 200 mg LY2584702 QD | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing | AUC(0-inf), Day 1 | 30897 nanograms*hours/milliliter (ng*hr/mL) | — |
Secondary
Pharmacokinetics, Maximum Plasma Concentration (Cmax)
Cmax results on Day 1 and on Day 8 (steady state) are reported.
Time frame: Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, 8 hours postdose)
Population: All participants who received at least 1 dose of study drug and had evaluable Cmax data. In 300 mg LY2584702 BID group data was not analyzed for Cmax day 8 due to insufficient participants at the specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 1 | 425.79 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 42.2 |
| Part A | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 8 | 442.36 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49.2 |
| Part B | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 1 | 970.28 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 62.3 |
| Part B | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 8 | 991.74 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78.9 |
| 100 mg LY2584702 QD | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 1 | 446.43 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| 100 mg LY2584702 QD | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 8 | 1518.04 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 60.6 |
| 200 mg LY2584702 QD | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 8 | 1540.91 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78.9 |
| 200 mg LY2584702 QD | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 1 | 1428.74 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 66.7 |
| 50 mg LY2584702 BID | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 1 | 522.47 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 87.9 |
| 50 mg LY2584702 BID | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 8 | 841.58 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43.3 |
| 75 mg LY2584702 BID | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 1 | 1358.19 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57.1 |
| 75 mg LY2584702 BID | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 8 | 1347.12 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.3 |
| 100 mg LY2584702 BID | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 8 | 2529.26 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44.8 |
| 100 mg LY2584702 BID | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 1 | 1563.55 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56.5 |
| 300 mg LY2584702 BID | Pharmacokinetics, Maximum Plasma Concentration (Cmax) | Day 1 | 3409.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 65 |