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Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00402116
Collaborator
University of California, San Francisco (Other)
72
Enrollment
1
Location
1
Arm
39
Duration (Months)
1.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There will be 2 phases in this study. Patients will either be enrolled to the first phase or to the second phase, depending upon when they enroll into the study.

The first phase of this study is done to evaluate the safety of enzastaurin in patients. This is done by gradually increasing the dose of the drug in small groups of patients and watching closely for side effects.

In the second phase of the study, the dose determined to be safe will be used with temozolomide during and following radiation therapy to see if the combination can help patients with brain tumors live longer.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
72 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1/2 Study of Enzastaurin Plus Temozolomide During and Following Radiation Therapy in Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
Study Start Date :
Sep 1, 2006
Actual Primary Completion Date :
Dec 1, 2009
Actual Study Completion Date :
Dec 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: A

The Phase 1 consisted of the dose escalation of enzastaurin in 2 cohorts of up to 6 patients to assess maximum tolerated dose (MTD). Cohort 1 = radiotherapy/enzastaurin 250 mg per day/temozolomide 75 mg/m^2 therapy. The 6 initial cohort patients were clinically evaluated for dose-limiting toxicities (DLT). If no more than 1 of 6 patients experienced a DLT or tumor progression, patients continued 1 complete adjuvant enzastaurin/temozolomide 28-day cycle. If there was no significant toxicity after the first adjuvant cycle, participants received subsequent adjuvant enzastaurin/temozolomide cycles. If no more than 1 of the 6 initial cohort participants treated at 250 mg of enzastaurin experienced a DLT during radiotherapy and the first adjuvant cycle, up to 6 more participants could be entered at 500 mg of enzastaurin. The Phase 2, using the MTD determined in the Phase 1 (250 mg), evaluated the combination's safety and measured OS.

Drug: enzastaurin
Phase 1 - 250 mg Cohort 1 with one dose escalation allowed to 500 mg for Cohort 2, oral, daily, 6 weeks then twelve 28 day cycles Phase 2 - Phase 1 established dose, oral, daily, 6 weeks then twelve 28 day cycles
Other Names:
  • LY317615

    • Drug: temozolomide
    75 milligrams per meter squared (mg/m^2), oral, daily, 6 weeks then 200 mg/m^2, oral, daily, twelve 28 day cycles

    Radiation: radiation therapy
    1.8-2.0 Gy x 30 fractions, 5 days/week, for 6 weeks

    Outcome Measures

    Primary Outcome Measures

    1. Phase 1- Determination of the Maximum Tolerated Dose (MTD) of Enzastaurin [Until MTD can be determined (up to 12 cycles, 28 days per cycle)]

      Phase 1- dose escalation of enzastaurin in 2 cohorts up to 6 participants each in order to assess MTD. After radiation/enzastaurin 250 mg per day/temozolomide 75 mg/m^2 therapy, if no more than 1 of 6 patients experienced a dose-limiting toxicity (DLT) or tumor progression, participants completed one 28-day cycle. If no significant toxicity after the first cycle, participants received subsequent cycles. If no more than 1 of the 6 patients treated at 250 mg of enzastaurin experienced a DLT, up to 6 more patients could be entered at escalated dose cohort of enzastaurin (500 mg).

    2. Phase 1 and Phase 2 - Overall Survival (OS) [Baseline to death from any cause (Up to 48 weeks)]

      OS is the time from surgical diagnosis to the date of death from any cause. For participants who were alive, OS was censored at the last contact.

    Secondary Outcome Measures

    1. Phase 1 - Number of Participants With Adverse Events (AEs) [Every cycle (up to 12 cycles, 28 days per cycle)]

      Summaries of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module.

    2. Phase 1 and 2: Association Between Biomarkers and Clinical Outcome [Baseline, Cycle 2, end of study (up to 12 cycles, 28 days per cycle)]

      Phosphorylated-S6 (pS6) ribosomal protein is a biomarker that's being investigated as a potential marker for clinical outcome using 2211 or 2215 antibody to pS6. Reported here are the hazard ratios and 95% confidence intervals (CIs) for participants for whom an pS6 immunohistochemistry (IHC) score was available. The IHC assays were scored using a 0 to +3 scoring system (no positive staining was scored 0; at least 25% immunoreactivity of cells was scored +1; 26% to 75% was scored +2; and 76% or greater was scored +3). Hazard ratio (HR) > 1 indicates worse outcome for that IHC score.

    3. Phase 1 - Response Rate With Macdonald Criteria [Baseline, following radiation, every other cycle (up to 12 cycles, 28 days per cycle)]

      Response categories: complete response (CR): disappearance of all enhancing tumor on consecutive magnetic resonance imaging (MRI) scans at least 1 month apart, off steroids, and neurologically stable or improved. Partial response (PR): 50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved. Progressive disease (PD): >25% increase in size of enhancing tumor or any new tumor on MRI scans, or neurologically worse, and steroids stable or increased. Stable disease (SD): all other situations.

    4. Phase 2 - Number of Participants With Adverse Events (AEs) [Every cycle (28 days per cycle)]

      Summaries of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module.

    5. Number of Participants Undergoing Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS) for Clinical Evaluation at Baseline [Each radiologic assessment (up to 12 cycles, 28 days per cycle)]

      Number of patients having MRI/MRS for clinical evaluation with baseline assessment.

    6. Phase 1 and 2 - Progression-Free Survival (PFS) [Baseline to measured progressive disease (up to 12 cycles, 28 days per cycle)]

      PFS was defined as the time from date of first dose to the first observation of disease progression, or death due to any cause.

    7. Functional Assessment of Cancer Therapy - Brain (FACT-Br) [Every cycle (up to 12 cycles, 28 days per cycle)]

      Total FACT-Br score includes physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns related to brain tumors. The score ranges 0 to 200, with a higher score representing better quality of life.

    8. M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT) [Every cycle (up to 12 cycles, 28 days per cycle)]

      General and brain tumor-specific symptoms each assessed on a scale of 0 to 10, with a higher score representing higher symptom burden. The 4 symptom scales reported as changing over the course of the study are listed here.

    9. Phase 1- Pharmacokinetics (PK): Maximum Observed Drug Concentration During 1 Dosing Interval at Steady State (Cmax,ss) for Enzastaurin, LY326020, and Total Analyte (Enzastaurin + LY326020) When Enzastaurin Administered With or Without Temozolomide [Cycle 1 Day 22, Cycle 2 Day 5, 28 days per Cycle]

      Cmax,ss was calculated using concentration versus time data of enzastaurin, LY326020, and Total Analyte (enzastaurin + LY326020) when 250 mg or 500 mg enzastaurin was administered alone or with 75 mg/m^2 temozolomide. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).

    10. Phase 1 and 2- Pharmacokinetics: Area Under the Concentration-Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) for Enzastaurin, LY326020 and Total Analyte (Enzastaurin + LY326020) When Enzastaurin Administered With or Without Temozolomide [Phase 1, Cycle 1 Day 22, Cycle 2 Day 5 of a 28 day Cycle; Phase 2, Cycle 1 Day 22 of a 28 day Cycle]

      AUCτ,ss was calculated using concentration versus time data of enzastaurin, LY326020, and total analyte (enzastaurin + LY326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patients must have a histologically confirmed diagnosis of intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS).

    • Biopsy or resection must have been performed no more than 5 weeks prior to treatment.

    • An MRI or CT scan must be obtained within 14 days prior to treatment.

    • Patients must not have received prior drug therapy for brain tumors.

    • Patients must have adequate organ function demonstrated by lab tests within 14 days prior to treatment.

    Exclusion Criteria:

    • Patients will be excluded if unable to swallow tablets.

    • Patients will be excluded if unable to discontinue use of enzyme inducing antiepileptic drugs or have been off of these agents less than 2 weeks prior to treatment (i.e. phenytoin (Dilantin®), carbamazepine, etc.).

    • Patients will be excluded if have active infection.

    • Patients will be excluded if have a significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.

    • Patients will be excluded if they have concurrent therapy with an anticoagulant. If the patient requires anticoagulant therapy after starting treatment, the patient may remain on study but should be monitored carefully.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559), Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician San Francisco California United States

    Sponsors and Collaborators

    • Eli Lilly and Company
    • University of California, San Francisco

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00402116
    Other Study ID Numbers:
    • 9815
    • H6Q-MC-S008
    First Posted:
    Nov 22, 2006
    Last Update Posted:
    Aug 6, 2020
    Last Verified:
    Jul 1, 2020
    Additional relevant MeSH terms:
    Glioblastoma
    Gliosarcoma
    Temozolomide

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 12 participants entered Phase 1 of the study. A total of 60 participants were analyzed in Phase 2 for a total of 72 participants for both phases.
    Arm/Group Title Phase 1- Cohort 1 (250 mg Enzastaurin) Phase 1 Cohort 2 (500 mg Enzastaurin) Phase 2
    Arm/Group Description Phase 1--Determination of the maximum tolerated dose (MTD) of enzastaurin in participants with newly diagnosed GBM or GS receiving a 250 mg dose - Cohort 1. Phase 1--Determination of the maximum tolerated dose (MTD) of enzastaurin in participants with newly diagnosed GBM or GS receiving a 500 mg dose - Cohort 2. Phase 1 established dose (250 mg), daily for 6 weeks, then twelve 28-day cycles.
    Period Title: Overall Study
    STARTED 6 6 60
    COMPLETED 3 0 5
    NOT COMPLETED 3 6 55

    Baseline Characteristics

    Arm/Group Title Phase 1- Cohort 1 (250 mg Enzastaurin) Phase 1 Cohort 2 (500 mg Enzastaurin ) Phase 2 Total
    Arm/Group Description Participants who received 250 mg enzastaurin in Phase I with 75 mg/m^2 temozolomide and radiotherapy. Participants who received 500 mg enzastaurin in Phase I with 75 mg/m^2 temozolomide and radiotherapy. Participants who received 250 mg enzastaurin in Phase II with 75 mg/m^2 temozolomide and radiotherapy. Total of all reporting groups
    Overall Participants 6 6 60 72
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    48.0
    (7.54)
    52.5
    (13.84)
    55.3
    (10.95)
    54.7
    (10.85)
    Sex: Female, Male (Count of Participants)
    Female
    1
    16.7%
    3
    50%
    17
    28.3%
    21
    29.2%
    Male
    5
    83.3%
    3
    50%
    43
    71.7%
    51
    70.8%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    0
    0%
    1
    16.7%
    4
    6.7%
    5
    6.9%
    White
    6
    100%
    3
    50%
    52
    86.7%
    61
    84.7%
    Unknown
    0
    0%
    2
    33.3%
    4
    6.7%
    6
    8.3%
    Region of Enrollment (Count of Participants)
    United States
    6
    100%
    6
    100%
    60
    100%
    72
    100%

    Outcome Measures

    1. Primary Outcome
    Title Phase 1- Determination of the Maximum Tolerated Dose (MTD) of Enzastaurin
    Description Phase 1- dose escalation of enzastaurin in 2 cohorts up to 6 participants each in order to assess MTD. After radiation/enzastaurin 250 mg per day/temozolomide 75 mg/m^2 therapy, if no more than 1 of 6 patients experienced a dose-limiting toxicity (DLT) or tumor progression, participants completed one 28-day cycle. If no significant toxicity after the first cycle, participants received subsequent cycles. If no more than 1 of the 6 patients treated at 250 mg of enzastaurin experienced a DLT, up to 6 more patients could be entered at escalated dose cohort of enzastaurin (500 mg).
    Time Frame Until MTD can be determined (up to 12 cycles, 28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    All Phase I participants who received at least one dose of study drug.
    Arm/Group Title Phase 1 Participants
    Arm/Group Description Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m^2 temozolomide and radiotherapy.
    Measure Participants 12
    Number [milligrams (mg)]
    250
    2. Primary Outcome
    Title Phase 1 and Phase 2 - Overall Survival (OS)
    Description OS is the time from surgical diagnosis to the date of death from any cause. For participants who were alive, OS was censored at the last contact.
    Time Frame Baseline to death from any cause (Up to 48 weeks)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 participants combined with Phase 1 cohort 1 participants who also received 250 mg enzastaurin.
    Arm/Group Title 250 mg Enzastaurin Phases 1 and 2 Combined
    Arm/Group Description Phase 2 participants combined with Phase 1 - Cohort 1 participants who also received 250 mg enzastaurin.
    Measure Participants 66
    Median (95% Confidence Interval) [months]
    18.3
    3. Secondary Outcome
    Title Phase 1 - Number of Participants With Adverse Events (AEs)
    Description Summaries of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module.
    Time Frame Every cycle (up to 12 cycles, 28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    All Phase I participants who received at least one dose of study drug.
    Arm/Group Title Phase 1- Cohort 1 (250 mg Enzastaurin) Phase 1 Cohort 2 (500 mg Enzastaurin )
    Arm/Group Description Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 1 (250 mg Enzastaurin) participants Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
    Measure Participants 6 6
    Count of Participants [Participants]
    0
    0%
    1
    16.7%
    4. Secondary Outcome
    Title Phase 1 and 2: Association Between Biomarkers and Clinical Outcome
    Description Phosphorylated-S6 (pS6) ribosomal protein is a biomarker that's being investigated as a potential marker for clinical outcome using 2211 or 2215 antibody to pS6. Reported here are the hazard ratios and 95% confidence intervals (CIs) for participants for whom an pS6 immunohistochemistry (IHC) score was available. The IHC assays were scored using a 0 to +3 scoring system (no positive staining was scored 0; at least 25% immunoreactivity of cells was scored +1; 26% to 75% was scored +2; and 76% or greater was scored +3). Hazard ratio (HR) > 1 indicates worse outcome for that IHC score.
    Time Frame Baseline, Cycle 2, end of study (up to 12 cycles, 28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    Combined Phases 1 and 2 populations for whom IHC scores were obtained. HR > 1 indicates poorer overall survival for that IHC score.
    Arm/Group Title 250 mg Enzastaurin Phases 1 and 2 Combined
    Arm/Group Description Participants with valid IHC scores from combined Phase 1 and 2 populations 250 mg enzastaurin.
    Measure Participants 49
    S6 2211 score
    1.70
    S6 2215 score
    1.69
    5. Secondary Outcome
    Title Phase 1 - Response Rate With Macdonald Criteria
    Description Response categories: complete response (CR): disappearance of all enhancing tumor on consecutive magnetic resonance imaging (MRI) scans at least 1 month apart, off steroids, and neurologically stable or improved. Partial response (PR): 50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, and neurologically stable or improved. Progressive disease (PD): >25% increase in size of enhancing tumor or any new tumor on MRI scans, or neurologically worse, and steroids stable or increased. Stable disease (SD): all other situations.
    Time Frame Baseline, following radiation, every other cycle (up to 12 cycles, 28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    Efficacy analysis in phase I was not conducted. Instead, participants who took 250mg in phase I were pooled with phase II participants and are presented in other outcome measures (2 and 8, respectively) in this record. Thus there were 0 participants for this measure.
    Arm/Group Title 250 mg Enzastaurin Phases 1 and 2 Combined
    Arm/Group Description Efficacy analysis in Phase 1 was not conducted. Instead, participants who took 250 mg enzastaurin in Phase 1 were pooled with Phase 2 participants. Overall survival (OS) and progression-free survival (PFS) for this combined group are presented in other outcome measures (2 and 8, respectively) in this result record.
    Measure Participants 0
    6. Secondary Outcome
    Title Phase 2 - Number of Participants With Adverse Events (AEs)
    Description Summaries of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module.
    Time Frame Every cycle (28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    All Phase 2 participants who received at least one dose of study drug.
    Arm/Group Title Phase 2 - 250 mg Enzastaurin
    Arm/Group Description Summaries of SAEs and all other non-serious AEs for Phase 2 - 250 mg Enzastaurin participants are located in the Reported Adverse Event Module.
    Measure Participants 60
    Count of Participants [Participants]
    22
    366.7%
    7. Secondary Outcome
    Title Number of Participants Undergoing Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS) for Clinical Evaluation at Baseline
    Description Number of patients having MRI/MRS for clinical evaluation with baseline assessment.
    Time Frame Each radiologic assessment (up to 12 cycles, 28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    35 patients underwent MRI and had baseline measurement.
    Arm/Group Title Phase 2 - 250 mg
    Arm/Group Description Participants who underwent magnetic resonance imaging (MRI) for clinical evaluation and had a baseline assessment.
    Measure Participants 35
    Count of Participants [Participants]
    35
    583.3%
    8. Secondary Outcome
    Title Phase 1 and 2 - Progression-Free Survival (PFS)
    Description PFS was defined as the time from date of first dose to the first observation of disease progression, or death due to any cause.
    Time Frame Baseline to measured progressive disease (up to 12 cycles, 28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    Phase 2 participants combined with Phase 1 cohort 1 participants who also received 250 mg enzastaurin.
    Arm/Group Title 250 mg Enzastaurin Phases 1 and 2 Combined
    Arm/Group Description All treated participants in the 250 mg enzastaurin cohort from Phases 1 and 2 combined
    Measure Participants 66
    Median (95% Confidence Interval) [months]
    10.6
    9. Secondary Outcome
    Title Functional Assessment of Cancer Therapy - Brain (FACT-Br)
    Description Total FACT-Br score includes physical well-being, social/family well-being, emotional well-being, functional well-being and additional concerns related to brain tumors. The score ranges 0 to 200, with a higher score representing better quality of life.
    Time Frame Every cycle (up to 12 cycles, 28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    All treated participants who received at least one dose of study drug in the 250 mg enzastaurin cohort from Phases 1 and 2 combined and who also provided FACT-Br data from at least 1 visit (N = 65). One participant lacked these data.
    Arm/Group Title 250 mg Enzastaurin Phases 1 and 2 Combined
    Arm/Group Description All treated participants in the 250 mg enzastaurin cohort from phases 1 and 2 combined.
    Measure Participants 65
    Baseline visit
    153.5
    (24.08)
    Radiation therapy visit
    156.1
    (23.30)
    Cycle 1
    151.9
    (26.87)
    Cycle 2
    152.0
    (30.67)
    Cycle 3
    158.9
    (22.10)
    Cycle 4
    158.8
    (24.48)
    Cycle 5
    158.3
    (26.30)
    Cycle 6
    159.0
    (26.46)
    Cycle 7
    164.1
    (19.45)
    Cycle 8
    163.6
    (23.19)
    Cycle 9
    162.0
    (21.89)
    Cycle 10
    159.3
    (27.02)
    Cycle 11
    158.2
    (24.98)
    Cycle 12
    163.5
    (26.67)
    10. Secondary Outcome
    Title M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
    Description General and brain tumor-specific symptoms each assessed on a scale of 0 to 10, with a higher score representing higher symptom burden. The 4 symptom scales reported as changing over the course of the study are listed here.
    Time Frame Every cycle (up to 12 cycles, 28 days per cycle)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Enzastaurin 250 mg Phases 1 and 2 Combined-Fatigue Enzastaurin 250 mg Phase 1 and 2 Combined-Memory Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
    Arm/Group Description All treated participants who received at least 1 dose of study drug in the 250 mg enzastaurin cohort from Phases 1 and 2 combined and provided MDASI-BT data from at least 1 visit. Question: Your fatigue (tiredness) at its WORST? All treated participants who received at least 1 dose of study drug in the 250 mg enzastaurin cohort from Phases 1 and 2 combined and provided MDASI-BT data from at least 1 visit (N = 65). Question: Your problem with remembering things at its WORST? All treated participants who received at least 1 dose of study drug in the 250 mg enzastaurin cohort from Phases 1 and 2 combined and provided MDASI-BT data from at least 1 visit. Question: Your problem with lack of appetite at its WORST? All treated participants who received at least 1 dose of study drug in the 250 mg enzastaurin cohort from Phases 1 and 2 combined and provided MDASI-BT data from at least 1 visit. Question: Your difficulty concentrating at its WORST?
    Measure Participants 65 65 65 65
    Baseline
    2.4
    (2.1)
    1.8
    (2.6)
    0.3
    (1.1)
    1.2
    (1.9)
    Radiation therapy visit
    3.3
    (2.1)
    2.2
    (2.3)
    1.0
    (1.9)
    1.4
    (1.7)
    Cycle 1
    3.6
    (2.5)
    2.4
    (2.6)
    1.6
    (2.4)
    1.8
    (2.2)
    Cycle 2
    3.7
    (2.7)
    2.5
    (3.0)
    1.8
    (2.5)
    1.9
    (2.2)
    Cycle 3
    3.2
    (2.5)
    2.0
    (1.9)
    1.4
    (2.3)
    1.5
    (1.8)
    Cycle 4
    2.6
    (2.1)
    1.9
    (1.6)
    1.0
    (1.8)
    1.5
    (1.6)
    Cycle 5
    3.3
    (2.5)
    2.1
    (2.4)
    0.6
    (1.6)
    1.6
    (2.1)
    Cycle 6
    2.9
    (2.4)
    1.6
    (1.3)
    0.7
    (1.2)
    1.2
    (1.7)
    Cycle 7
    2.8
    (2.4)
    1.4
    (1.3)
    0.7
    (1.4)
    1.3
    (1.6)
    Cycle 8
    2.6
    (2.4)
    1.4
    (1.5)
    0.5
    (0.9)
    1.1
    (1.3)
    Cycle 9
    2.8
    (2.5)
    1.8
    (1.6)
    1.0
    (1.9)
    1.1
    (1.5)
    Cycle 10
    1.9
    (1.9)
    1.5
    (1.9)
    0.4
    (1.2)
    1.2
    (1.3)
    Cycle 11
    3.0
    (2.8)
    1.6
    (2.6)
    0.2
    (0.6)
    0.9
    (1.6)
    Cycle 12
    1.7
    (1.8)
    1.2
    (0.9)
    0.4
    (0.7)
    1.2
    (1.6)
    11. Secondary Outcome
    Title Phase 1- Pharmacokinetics (PK): Maximum Observed Drug Concentration During 1 Dosing Interval at Steady State (Cmax,ss) for Enzastaurin, LY326020, and Total Analyte (Enzastaurin + LY326020) When Enzastaurin Administered With or Without Temozolomide
    Description Cmax,ss was calculated using concentration versus time data of enzastaurin, LY326020, and Total Analyte (enzastaurin + LY326020) when 250 mg or 500 mg enzastaurin was administered alone or with 75 mg/m^2 temozolomide. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
    Time Frame Cycle 1 Day 22, Cycle 2 Day 5, 28 days per Cycle

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected. One participant dose was reduced from 500 mg to 250 mg after Cycle 1 Day 1 so is included in the 250 mg dose group (N=7).
    Arm/Group Title Enzastaurin 250 mg Enzastaurin 250 mg + Temozolomide Enzastaurin 500 mg Enzastaurin 500 mg + Temozolomide
    Arm/Group Description Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral (po) daily QD) for Phase 1 Cohort 1. Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 2 Day 5 (enzastaurin with temozolomide) following enzastaurin 250 mg oral (po) daily QD) for Phase 1 Cohort 1. Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 2 Day 5 (enzastaurin alone) following enzastaurin 500 mg oral (po) daily QD) for Phase 1 Cohort 2. Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 2 Day 5 (enzastaurin with temozolomide) following enzastaurin 500 mg oral (po) daily QD) for Phase 1 Cohort 2.
    Measure Participants 7 6 3 3
    Enzastaurin
    504
    (52)
    458
    (41)
    1350
    (149)
    719
    (114)
    LY326020
    370
    (38)
    392
    (27)
    198
    (274)
    465
    (87)
    Total Analyte
    853
    (44)
    821
    (28)
    1570
    (159)
    1010
    (114)
    12. Secondary Outcome
    Title Phase 1 and 2- Pharmacokinetics: Area Under the Concentration-Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) for Enzastaurin, LY326020 and Total Analyte (Enzastaurin + LY326020) When Enzastaurin Administered With or Without Temozolomide
    Description AUCτ,ss was calculated using concentration versus time data of enzastaurin, LY326020, and total analyte (enzastaurin + LY326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
    Time Frame Phase 1, Cycle 1 Day 22, Cycle 2 Day 5 of a 28 day Cycle; Phase 2, Cycle 1 Day 22 of a 28 day Cycle

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected. In Phase I, one participant dose was reduced from 500 mg to 250 mg after Cycle 1 Day 1 so was included in 250 mg dose group (N=7).
    Arm/Group Title Enzastaurin 250 mg Phase 1 Enzastaurin 250 mg + Temozolomide Enzastaurin 250 mg Phase 2 Enzastaurin 500 mg Enzastaurin 500 mg + Temozolomide
    Arm/Group Description Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg orally (po) daily (QID) for Phase 1 Cohort 1. Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 2 Day 5 (enzastaurin with temozolomide) following enzastaurin 250 mg po QID for Phase 1 Cohort 1. Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 500 mg oral po QID for Phase 1 Cohort 2 Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 2 Day 5 (enzastaurin with temozolomide) following enzastaurin 500 mg oral po QID for Phase 1 Cohort 2. Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
    Measure Participants 7 6 33 3 3
    Enzastaurin
    5390
    (57)
    5270
    (36)
    7720
    (91)
    16600
    (274)
    10100
    (133)
    LY326020
    7260
    (35)
    7380
    (22)
    12800
    (38)
    4240
    (283)
    8650
    (95)
    Total Analyte
    12800
    (41)
    12800
    (19)
    21400
    (53)
    21300
    (256)
    18900
    (114)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Phase 1- Cohort 1 (250 mg Enzastaurin) Phase 1 Cohort 2 (500 mg Enzastaurin) Phase 2 - 250 mg Enzastaurin
    Arm/Group Description Phase 1--Determination of the maximum tolerated dose (MTD) of enzastaurin in participants with newly diagnosed GBM or GS receiving a 250 mg dose. Phase 1--Determination of the maximum tolerated dose (MTD) of enzastaurin in participants with newly diagnosed GBM or GS receiving a 500 mg dose. Participants received 250 mg enzastaurin daily for 6 weeks, then twelve 28-day cycles.
    All Cause Mortality
    Phase 1- Cohort 1 (250 mg Enzastaurin) Phase 1 Cohort 2 (500 mg Enzastaurin) Phase 2 - 250 mg Enzastaurin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Phase 1- Cohort 1 (250 mg Enzastaurin) Phase 1 Cohort 2 (500 mg Enzastaurin) Phase 2 - 250 mg Enzastaurin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 1/6 (16.7%) 22/60 (36.7%)
    Blood and lymphatic system disorders
    Lymphopenia 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Thrombocytopenia 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Cardiac disorders
    Atrial fibrillation 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Endocrine disorders
    Adrenal insufficiency 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    General disorders
    Asthenia 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Disease progression 0/6 (0%) 0 1/6 (16.7%) 1 2/60 (3.3%) 2
    Fatigue 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Systemic leakage 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Infections and infestations
    Gastroenteritis 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Infection 0/6 (0%) 0 0/6 (0%) 0 2/60 (3.3%) 2
    Pneumonia 0/6 (0%) 0 0/6 (0%) 0 4/60 (6.7%) 4
    Urinary tract infection 0/6 (0%) 0 0/6 (0%) 0 2/60 (3.3%) 2
    Injury, poisoning and procedural complications
    Vascular access complication 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 2
    Metabolism and nutrition disorders
    Hyponatremia 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Nervous system disorders
    Cognitive disorder 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Complex partial seizure 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Convulsion 0/6 (0%) 0 0/6 (0%) 0 4/60 (6.7%) 4
    Encephalopathy 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Headache 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Hydrocephalus 0/6 (0%) 0 0/6 (0%) 0 2/60 (3.3%) 2
    Muscular weakness 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Myelitis 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Peripheral motor neuropathy 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Speech disorder 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Syncope 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Psychiatric disorders
    Confusional state 0/6 (0%) 0 0/6 (0%) 0 2/60 (3.3%) 2
    Delirium 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Depression 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Vascular disorders
    Deep vein thrombosis 0/6 (0%) 0 0/6 (0%) 0 2/60 (3.3%) 2
    Embolism 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Pulmonary embolism 0/6 (0%) 0 0/6 (0%) 0 1/60 (1.7%) 1
    Thrombosis 0/6 (0%) 0 0/6 (0%) 0 2/60 (3.3%) 2
    Other (Not Including Serious) Adverse Events
    Phase 1- Cohort 1 (250 mg Enzastaurin) Phase 1 Cohort 2 (500 mg Enzastaurin) Phase 2 - 250 mg Enzastaurin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 6/6 (100%) 60/60 (100%)
    Blood and lymphatic system disorders
    Leukopenia 4/6 (66.7%) 4 4/6 (66.7%) 4 16/60 (26.7%) 16
    Lymphopenia 5/6 (83.3%) 5 6/6 (100%) 6 52/60 (86.7%) 52
    Cardiac disorders
    Cardiac disorder 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Ear and labyrinth disorders
    Auditory disorder 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Ear pain 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Hearing loss 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Tinnitus 0/6 (0%) 0 0/6 (0%) 0 5/60 (8.3%) 5
    Endocrine disorders
    Adrenal insufficiency 0/6 (0%) 0 0/6 (0%) 0 3/60 (5%) 3
    Cushingoid 1/6 (16.7%) 1 0/6 (0%) 0 3/60 (5%) 3
    Eye disorders
    Diplopia 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Vision blurred 0/6 (0%) 0 2/6 (33.3%) 2 2/60 (3.3%) 2
    Gastrointestinal disorders
    Abdominal distension 0/6 (0%) 0 1/6 (16.7%) 1 1/60 (1.7%) 1
    Abdominal pain 1/6 (16.7%) 1 1/6 (16.7%) 1 2/60 (3.3%) 2
    Anal hemorrhage 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Constipation 6/6 (100%) 6 4/6 (66.7%) 4 42/60 (70%) 42
    Diarrhea 4/6 (66.7%) 4 2/6 (33.3%) 2 9/60 (15%) 9
    Dyspepsia 1/6 (16.7%) 1 2/6 (33.3%) 2 5/60 (8.3%) 5
    Feces discolored 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Flatulence 1/6 (16.7%) 1 1/6 (16.7%) 1 0/60 (0%) 0
    Gastritis 1/6 (16.7%) 1 0/6 (0%) 0 1/60 (1.7%) 1
    Gastrointestinal disorder 1/6 (16.7%) 1 0/6 (0%) 0 2/60 (3.3%) 2
    Hemorrhoids 0/6 (0%) 0 0/6 (0%) 0 3/60 (5%) 3
    Nausea 6/6 (100%) 6 4/6 (66.7%) 4 34/60 (56.7%) 34
    Oral hemorrhage 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Oral pain 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Periodontal disease 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Toothache 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Vomiting 4/6 (66.7%) 4 1/6 (16.7%) 1 14/60 (23.3%) 14
    General disorders
    Calcinosis 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Chills 0/6 (0%) 0 1/6 (16.7%) 1 1/60 (1.7%) 1
    Edema 0/6 (0%) 0 0/6 (0%) 0 3/60 (5%) 3
    Edema limbs 0/6 (0%) 0 0/6 (0%) 0 5/60 (8.3%) 5
    Facial pain 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Fatigue 6/6 (100%) 6 6/6 (100%) 6 52/60 (86.7%) 52
    Fever 2/6 (33.3%) 2 0/6 (0%) 0 2/60 (3.3%) 2
    Flu-like illness 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Flu-like symptoms 1/6 (16.7%) 1 0/6 (0%) 0 1/60 (1.7%) 1
    Pain 0/6 (0%) 0 0/6 (0%) 0 3/60 (5%) 3
    Hepatobiliary disorders
    Hyperbilirubinemia 1/6 (16.7%) 1 0/6 (0%) 0 13/60 (21.7%) 14
    Immune system disorders
    Allergic reaction 1/6 (16.7%) 1 1/6 (16.7%) 1 4/60 (6.7%) 4
    Hypersensitivity 0/6 (0%) 0 1/6 (16.7%) 1 1/60 (1.7%) 1
    Infections and infestations
    Bladder infection 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Bone infection 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Infection 2/6 (33.3%) 2 1/6 (16.7%) 1 3/60 (5%) 3
    Nasopharyngitis 0/6 (0%) 0 1/6 (16.7%) 1 5/60 (8.3%) 5
    Rhinitis 2/6 (33.3%) 2 0/6 (0%) 0 0/60 (0%) 0
    Sinusitis 1/6 (16.7%) 1 0/6 (0%) 0 5/60 (8.3%) 5
    Upper respiratory infection 2/6 (33.3%) 2 0/6 (0%) 0 3/60 (5%) 3
    Upper respiratory tract infection 1/6 (16.7%) 1 0/6 (0%) 0 2/60 (3.3%) 2
    Urinary tract infection 0/6 (0%) 0 1/6 (16.7%) 1 3/60 (5%) 3
    Wound infection 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Injury, poisoning and procedural complications
    Radiation recall reaction (dermatologic) 0/6 (0%) 0 1/6 (16.7%) 1 9/60 (15%) 9
    Wound complication 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Investigations
    Alanine aminotransferase increased 4/6 (66.7%) 4 2/6 (33.3%) 2 14/60 (23.3%) 14
    Alkaline phosphatase increased 1/6 (16.7%) 1 1/6 (16.7%) 1 3/60 (5%) 3
    Aspartate aminotransferase increased 3/6 (50%) 3 2/6 (33.3%) 2 10/60 (16.7%) 10
    Creatinine increased 2/6 (33.3%) 2 2/6 (33.3%) 2 6/60 (10%) 6
    Ear, nose and throat examination abnormal 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Hemoglobin 3/6 (50%) 3 1/6 (16.7%) 1 29/60 (48.3%) 29
    Hemoglobin decreased 2/6 (33.3%) 2 3/6 (50%) 3 13/60 (21.7%) 13
    International normalized ratio 1/6 (16.7%) 1 0/6 (0%) 0 2/60 (3.3%) 2
    Leukocyte count decreased 2/6 (33.3%) 2 1/6 (16.7%) 1 30/60 (50%) 30
    Neutrophil count decreased 2/6 (33.3%) 2 3/6 (50%) 3 7/60 (11.7%) 7
    Neutrophils 1/6 (16.7%) 1 0/6 (0%) 0 11/60 (18.3%) 11
    Platelet count decreased 5/6 (83.3%) 5 3/6 (50%) 3 12/60 (20%) 12
    Platelets decreased 2/6 (33.3%) 2 3/6 (50%) 3 23/60 (38.3%) 23
    Proctoscopy abnormal 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Weight gain 3/6 (50%) 3 0/6 (0%) 0 3/60 (5%) 3
    Weight loss 2/6 (33.3%) 2 3/6 (50%) 3 8/60 (13.3%) 8
    Metabolism and nutrition disorders
    Anorexia 4/6 (66.7%) 4 3/6 (50%) 3 26/60 (43.3%) 26
    Dehydration 0/6 (0%) 0 1/6 (16.7%) 1 1/60 (1.7%) 1
    Hypercholesterolemia 1/6 (16.7%) 1 0/6 (0%) 0 3/60 (5%) 3
    Hyperglycemia 5/6 (83.3%) 5 1/6 (16.7%) 1 38/60 (63.3%) 39
    Hyperkalemia 1/6 (16.7%) 1 0/6 (0%) 0 6/60 (10%) 6
    Hypermagnesemia 0/6 (0%) 0 0/6 (0%) 0 4/60 (6.7%) 4
    Hypernatremia 1/6 (16.7%) 1 1/6 (16.7%) 1 9/60 (15%) 9
    Hypoalbuminemia 1/6 (16.7%) 1 0/6 (0%) 0 12/60 (20%) 12
    Hypocalcemia 1/6 (16.7%) 1 0/6 (0%) 0 13/60 (21.7%) 13
    Hypoglycemia 3/6 (50%) 3 1/6 (16.7%) 1 8/60 (13.3%) 8
    Hypokalemia 1/6 (16.7%) 1 3/6 (50%) 3 13/60 (21.7%) 13
    Hyponatremia 1/6 (16.7%) 1 1/6 (16.7%) 1 12/60 (20%) 12
    Musculoskeletal and connective tissue disorders
    Back pain 4/6 (66.7%) 4 1/6 (16.7%) 1 6/60 (10%) 6
    Buttock pain 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Joint disorder 2/6 (33.3%) 2 0/6 (0%) 0 4/60 (6.7%) 4
    Joint pain 1/6 (16.7%) 1 2/6 (33.3%) 2 4/60 (6.7%) 4
    Muscle weakness 0/6 (0%) 0 0/6 (0%) 0 3/60 (5%) 3
    Muscle weakness lower limb 0/6 (0%) 0 1/6 (16.7%) 1 4/60 (6.7%) 4
    Musculoskeletal disorder 2/6 (33.3%) 2 0/6 (0%) 0 2/60 (3.3%) 2
    Myalgia 0/6 (0%) 0 0/6 (0%) 0 13/60 (21.7%) 13
    Neck pain 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Pain in extremity 2/6 (33.3%) 2 1/6 (16.7%) 1 4/60 (6.7%) 4
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Uterine leiomyoma 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Nervous system disorders
    Ataxia 1/6 (16.7%) 1 3/6 (50%) 3 5/60 (8.3%) 5
    Central nervous system necrosis 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Cognitive disturbance 1/6 (16.7%) 1 1/6 (16.7%) 1 7/60 (11.7%) 7
    Convulsion 2/6 (33.3%) 2 2/6 (33.3%) 2 4/60 (6.7%) 4
    Depressed level of consciousness 0/6 (0%) 0 1/6 (16.7%) 1 3/60 (5%) 3
    Dizziness 2/6 (33.3%) 2 2/6 (33.3%) 2 7/60 (11.7%) 7
    Headache 2/6 (33.3%) 2 3/6 (50%) 3 29/60 (48.3%) 29
    Hydrocephalus 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Memory impairment 4/6 (66.7%) 4 2/6 (33.3%) 2 20/60 (33.3%) 20
    Neurologic disorder NOS 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Peripheral motor neuropathy 1/6 (16.7%) 1 1/6 (16.7%) 1 11/60 (18.3%) 11
    Peripheral sensory neuropathy 2/6 (33.3%) 2 3/6 (50%) 3 9/60 (15%) 9
    Speech disorder 1/6 (16.7%) 1 2/6 (33.3%) 2 11/60 (18.3%) 11
    Taste alteration 3/6 (50%) 3 0/6 (0%) 0 12/60 (20%) 12
    Tremor 1/6 (16.7%) 1 0/6 (0%) 0 6/60 (10%) 6
    Visual field defect 1/6 (16.7%) 1 1/6 (16.7%) 1 1/60 (1.7%) 1
    Psychiatric disorders
    Anxiety 2/6 (33.3%) 2 2/6 (33.3%) 2 11/60 (18.3%) 11
    Confusional state 0/6 (0%) 0 2/6 (33.3%) 2 10/60 (16.7%) 10
    Depression 2/6 (33.3%) 2 2/6 (33.3%) 2 14/60 (23.3%) 14
    Insomnia 1/6 (16.7%) 1 3/6 (50%) 3 20/60 (33.3%) 20
    Libido decreased 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Renal and urinary disorders
    Urinary frequency 1/6 (16.7%) 1 0/6 (0%) 0 5/60 (8.3%) 5
    Urinary incontinence 0/6 (0%) 0 1/6 (16.7%) 1 2/60 (3.3%) 2
    Urinary retention 0/6 (0%) 0 1/6 (16.7%) 1 1/60 (1.7%) 1
    Urine discoloration 4/6 (66.7%) 4 4/6 (66.7%) 4 8/60 (13.3%) 8
    Urogenital disorder 0/6 (0%) 0 0/6 (0%) 0 3/60 (5%) 4
    Reproductive system and breast disorders
    Erectile dysfunction 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Reproductive tract disorder 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Uterine pain 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Vaginal hemorrhage 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 1/6 (16.7%) 1 1/6 (16.7%) 1 8/60 (13.3%) 8
    Dyspnea 0/6 (0%) 0 0/6 (0%) 0 5/60 (8.3%) 5
    Hemorrhage nasal 2/6 (33.3%) 2 1/6 (16.7%) 1 3/60 (5%) 3
    Nasal congestion 1/6 (16.7%) 1 0/6 (0%) 0 1/60 (1.7%) 1
    Pharyngolaryngeal pain 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Pulmonary disorder 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Voice alteration 0/6 (0%) 0 0/6 (0%) 0 4/60 (6.7%) 4
    Skin and subcutaneous tissue disorders
    Acne 1/6 (16.7%) 1 0/6 (0%) 0 1/60 (1.7%) 1
    Alopecia 1/6 (16.7%) 1 2/6 (33.3%) 2 41/60 (68.3%) 41
    Dry skin 1/6 (16.7%) 1 0/6 (0%) 0 4/60 (6.7%) 4
    Pain of skin 0/6 (0%) 0 1/6 (16.7%) 1 0/60 (0%) 0
    Petechiae 0/6 (0%) 0 0/6 (0%) 0 4/60 (6.7%) 4
    Pruritus 0/6 (0%) 0 1/6 (16.7%) 1 5/60 (8.3%) 5
    Rash 1/6 (16.7%) 1 0/6 (0%) 0 8/60 (13.3%) 8
    Rash desquamating 3/6 (50%) 3 0/6 (0%) 0 2/60 (3.3%) 2
    Skin disorder 1/6 (16.7%) 1 1/6 (16.7%) 1 4/60 (6.7%) 4
    Sweating 0/6 (0%) 0 1/6 (16.7%) 1 3/60 (5%) 3
    Vascular disorders
    Phlebitis superficial 1/6 (16.7%) 1 0/6 (0%) 0 0/60 (0%) 0
    Thrombosis 2/6 (33.3%) 2 0/6 (0%) 0 0/60 (0%) 0
    Vascular disorder 2/6 (33.3%) 2 0/6 (0%) 0 0/60 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT00402116
    Other Study ID Numbers:
    • 9815
    • H6Q-MC-S008
    First Posted:
    Nov 22, 2006
    Last Update Posted:
    Aug 6, 2020
    Last Verified:
    Jul 1, 2020