Trial Outcomes & Findings for Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients (NCT NCT00402116)
NCT ID: NCT00402116
Last Updated: 2020-08-06
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
72 participants
Primary outcome timeframe
Until MTD can be determined (up to 12 cycles, 28 days per cycle)
Results posted on
2020-08-06
Participant Flow
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.
Participant milestones
| Measure |
Phase 1- Cohort 1 (250 mg Enzastaurin)
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 Cohort 2 (500 mg Enzastaurin)
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 2
Phase 1 established dose (250 mg), daily for 6 weeks, then twelve 28-day cycles.
|
|---|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
60
|
|
Overall Study
COMPLETED
|
3
|
0
|
5
|
|
Overall Study
NOT COMPLETED
|
3
|
6
|
55
|
Reasons for withdrawal
| Measure |
Phase 1- Cohort 1 (250 mg Enzastaurin)
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 Cohort 2 (500 mg Enzastaurin)
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 2
Phase 1 established dose (250 mg), daily for 6 weeks, then twelve 28-day cycles.
|
|---|---|---|---|
|
Overall Study
Jaw infection after surgery-other
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
5
|
|
Overall Study
Treatment completed per protocol
|
1
|
1
|
2
|
|
Overall Study
other complicating disease
|
0
|
0
|
2
|
|
Overall Study
Disease Progression
|
0
|
4
|
38
|
|
Overall Study
mistaken thrombocytopenia
|
0
|
0
|
1
|
|
Overall Study
decline related hyponatremia/tumor
|
0
|
0
|
1
|
|
Overall Study
Adverse Event
|
0
|
1
|
6
|
Baseline Characteristics
Phase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients
Baseline characteristics by cohort
| Measure |
Phase 1- Cohort 1 (250 mg Enzastaurin)
n=6 Participants
Participants who received 250 mg enzastaurin in Phase I with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
n=6 Participants
Participants who received 500 mg enzastaurin in Phase I with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 2
n=60 Participants
Participants who received 250 mg enzastaurin in Phase II with 75 mg/m\^2 temozolomide and radiotherapy.
|
Total
n=72 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
48.0 years
STANDARD_DEVIATION 7.54 • n=5 Participants
|
52.5 years
STANDARD_DEVIATION 13.84 • n=7 Participants
|
55.3 years
STANDARD_DEVIATION 10.95 • n=5 Participants
|
54.7 years
STANDARD_DEVIATION 10.85 • n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
61 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
72 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Until MTD can be determined (up to 12 cycles, 28 days per cycle)Population: All Phase I participants who received at least one dose of study drug.
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).
Outcome measures
| Measure |
Phase 1 Participants
n=12 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
Phase 1- Determination of the Maximum Tolerated Dose (MTD) of Enzastaurin
|
250 milligrams (mg)
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline to death from any cause (Up to 48 weeks)Population: Phase 2 participants combined with Phase 1 cohort 1 participants who also received 250 mg enzastaurin.
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.
Outcome measures
| Measure |
Phase 1 Participants
n=66 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
Phase 1 and Phase 2 - Overall Survival (OS)
|
18.3 months
Interval 15.2 to 19.3
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Every cycle (up to 12 cycles, 28 days per cycle)Population: All Phase I participants who received at least one dose of study drug.
Summaries of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module.
Outcome measures
| Measure |
Phase 1 Participants
n=6 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
n=6 Participants
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
Phase 1 - Number of Participants With Adverse Events (AEs)
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2, end of study (up to 12 cycles, 28 days per cycle)Population: Combined Phases 1 and 2 populations for whom IHC scores were obtained. HR \> 1 indicates poorer overall survival for that IHC score.
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.
Outcome measures
| Measure |
Phase 1 Participants
n=49 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
Phase 1 and 2: Association Between Biomarkers and Clinical Outcome
S6 2211 score
|
1.70 Hazard ratio
Interval 1.05 to 2.77
|
—
|
—
|
—
|
—
|
|
Phase 1 and 2: Association Between Biomarkers and Clinical Outcome
S6 2215 score
|
1.69 Hazard ratio
Interval 1.08 to 2.66
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, following radiation, every other cycle (up to 12 cycles, 28 days per cycle)Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Every cycle (28 days per cycle)Population: All Phase 2 participants who received at least one dose of study drug.
Summaries of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module.
Outcome measures
| Measure |
Phase 1 Participants
n=60 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
Phase 2 - Number of Participants With Adverse Events (AEs)
|
22 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Each radiologic assessment (up to 12 cycles, 28 days per cycle)Population: 35 patients underwent MRI and had baseline measurement.
Number of patients having MRI/MRS for clinical evaluation with baseline assessment.
Outcome measures
| Measure |
Phase 1 Participants
n=35 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
Number of Participants Undergoing Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS) for Clinical Evaluation at Baseline
|
35 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to measured progressive disease (up to 12 cycles, 28 days per cycle)Population: Phase 2 participants combined with Phase 1 cohort 1 participants who also received 250 mg enzastaurin.
PFS was defined as the time from date of first dose to the first observation of disease progression, or death due to any cause.
Outcome measures
| Measure |
Phase 1 Participants
n=66 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
Phase 1 and 2 - Progression-Free Survival (PFS)
|
10.6 months
Interval 8.4 to 12.7
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Every cycle (up to 12 cycles, 28 days per cycle)Population: 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.
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.
Outcome measures
| Measure |
Phase 1 Participants
n=65 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Baseline visit
|
153.5 units on a scale
Standard Deviation 24.08
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Radiation therapy visit
|
156.1 units on a scale
Standard Deviation 23.30
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 1
|
151.9 units on a scale
Standard Deviation 26.87
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 2
|
152.0 units on a scale
Standard Deviation 30.67
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 3
|
158.9 units on a scale
Standard Deviation 22.10
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 4
|
158.8 units on a scale
Standard Deviation 24.48
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 5
|
158.3 units on a scale
Standard Deviation 26.30
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 6
|
159.0 units on a scale
Standard Deviation 26.46
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 7
|
164.1 units on a scale
Standard Deviation 19.45
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 8
|
163.6 units on a scale
Standard Deviation 23.19
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 9
|
162.0 units on a scale
Standard Deviation 21.89
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 10
|
159.3 units on a scale
Standard Deviation 27.02
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 11
|
158.2 units on a scale
Standard Deviation 24.98
|
—
|
—
|
—
|
—
|
|
Functional Assessment of Cancer Therapy - Brain (FACT-Br)
Cycle 12
|
163.5 units on a scale
Standard Deviation 26.67
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Phase 1 Participants
n=65 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
n=65 Participants
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
n=65 Participants
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
n=65 Participants
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 4
|
2.6 units on a scale
Standard Deviation 2.1
|
1.9 units on a scale
Standard Deviation 1.6
|
1.0 units on a scale
Standard Deviation 1.8
|
1.5 units on a scale
Standard Deviation 1.6
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 5
|
3.3 units on a scale
Standard Deviation 2.5
|
2.1 units on a scale
Standard Deviation 2.4
|
0.6 units on a scale
Standard Deviation 1.6
|
1.6 units on a scale
Standard Deviation 2.1
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 7
|
2.8 units on a scale
Standard Deviation 2.4
|
1.4 units on a scale
Standard Deviation 1.3
|
0.7 units on a scale
Standard Deviation 1.4
|
1.3 units on a scale
Standard Deviation 1.6
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 8
|
2.6 units on a scale
Standard Deviation 2.4
|
1.4 units on a scale
Standard Deviation 1.5
|
0.5 units on a scale
Standard Deviation 0.9
|
1.1 units on a scale
Standard Deviation 1.3
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 9
|
2.8 units on a scale
Standard Deviation 2.5
|
1.8 units on a scale
Standard Deviation 1.6
|
1.0 units on a scale
Standard Deviation 1.9
|
1.1 units on a scale
Standard Deviation 1.5
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 10
|
1.9 units on a scale
Standard Deviation 1.9
|
1.5 units on a scale
Standard Deviation 1.9
|
0.4 units on a scale
Standard Deviation 1.2
|
1.2 units on a scale
Standard Deviation 1.3
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 11
|
3.0 units on a scale
Standard Deviation 2.8
|
1.6 units on a scale
Standard Deviation 2.6
|
0.2 units on a scale
Standard Deviation 0.6
|
0.9 units on a scale
Standard Deviation 1.6
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 12
|
1.7 units on a scale
Standard Deviation 1.8
|
1.2 units on a scale
Standard Deviation 0.9
|
0.4 units on a scale
Standard Deviation 0.7
|
1.2 units on a scale
Standard Deviation 1.6
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Baseline
|
2.4 units on a scale
Standard Deviation 2.1
|
1.8 units on a scale
Standard Deviation 2.6
|
0.3 units on a scale
Standard Deviation 1.1
|
1.2 units on a scale
Standard Deviation 1.9
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Radiation therapy visit
|
3.3 units on a scale
Standard Deviation 2.1
|
2.2 units on a scale
Standard Deviation 2.3
|
1.0 units on a scale
Standard Deviation 1.9
|
1.4 units on a scale
Standard Deviation 1.7
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 1
|
3.6 units on a scale
Standard Deviation 2.5
|
2.4 units on a scale
Standard Deviation 2.6
|
1.6 units on a scale
Standard Deviation 2.4
|
1.8 units on a scale
Standard Deviation 2.2
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 2
|
3.7 units on a scale
Standard Deviation 2.7
|
2.5 units on a scale
Standard Deviation 3.0
|
1.8 units on a scale
Standard Deviation 2.5
|
1.9 units on a scale
Standard Deviation 2.2
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 3
|
3.2 units on a scale
Standard Deviation 2.5
|
2.0 units on a scale
Standard Deviation 1.9
|
1.4 units on a scale
Standard Deviation 2.3
|
1.5 units on a scale
Standard Deviation 1.8
|
—
|
|
M.D. Anderson Symptom Inventory - Brain Tumor (MDASI-BT)
Cycle 6
|
2.9 units on a scale
Standard Deviation 2.4
|
1.6 units on a scale
Standard Deviation 1.3
|
0.7 units on a scale
Standard Deviation 1.2
|
1.2 units on a scale
Standard Deviation 1.7
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 Day 22, Cycle 2 Day 5, 28 days per CyclePopulation: 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).
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 (%).
Outcome measures
| Measure |
Phase 1 Participants
n=7 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
n=6 Participants
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
n=3 Participants
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
n=3 Participants
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?
|
Enzastaurin 500 mg + Temozolomide
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
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
LY326020
|
370 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 38
|
392 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 27
|
198 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 274
|
465 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 87
|
—
|
|
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
Total Analyte
|
853 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 44
|
821 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 28
|
1570 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 159
|
1010 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 114
|
—
|
|
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
Enzastaurin
|
504 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 52
|
458 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 41
|
1350 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 149
|
719 nanomole per liter (nmol/L)
Geometric Coefficient of Variation 114
|
—
|
SECONDARY outcome
Timeframe: 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 CyclePopulation: 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).
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 (%).
Outcome measures
| Measure |
Phase 1 Participants
n=7 Participants
Participants who received escalating doses of 250 mg and 500 mg enzastaurin in Phase 1 with 75 mg/m\^2 temozolomide and radiotherapy.
|
Phase 1 Cohort 2 (500 mg Enzastaurin )
n=6 Participants
Summaries of SAEs and all other non-serious AEs for Phase 1- Cohort 2 (500 mg Enzastaurin) participants
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Appetite
n=33 Participants
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?
|
Enzastaurin 250 mg Phase 1 and 2 Combined-Concentration
n=3 Participants
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?
|
Enzastaurin 500 mg + Temozolomide
n=3 Participants
Enzastaurin, LY326020 and total analyte (enzastaurin + LY326020) on Cycle 1 Day 22 (enzastaurin alone) following enzastaurin 250 mg oral po QID for Phase 2.
|
|---|---|---|---|---|---|
|
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
Enzastaurin
|
5390 nmol•h/L
Geometric Coefficient of Variation 57
|
5270 nmol•h/L
Geometric Coefficient of Variation 36
|
7720 nmol•h/L
Geometric Coefficient of Variation 91
|
16600 nmol•h/L
Geometric Coefficient of Variation 274
|
10100 nmol•h/L
Geometric Coefficient of Variation 133
|
|
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
Total Analyte
|
12800 nmol•h/L
Geometric Coefficient of Variation 41
|
12800 nmol•h/L
Geometric Coefficient of Variation 19
|
21400 nmol•h/L
Geometric Coefficient of Variation 53
|
21300 nmol•h/L
Geometric Coefficient of Variation 256
|
18900 nmol•h/L
Geometric Coefficient of Variation 114
|
|
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
LY326020
|
7260 nmol•h/L
Geometric Coefficient of Variation 35
|
7380 nmol•h/L
Geometric Coefficient of Variation 22
|
12800 nmol•h/L
Geometric Coefficient of Variation 38
|
4240 nmol•h/L
Geometric Coefficient of Variation 283
|
8650 nmol•h/L
Geometric Coefficient of Variation 95
|
Adverse Events
Phase 1- Cohort 1 (250 mg Enzastaurin)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase 1 Cohort 2 (500 mg Enzastaurin)
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase 2 - 250 mg Enzastaurin
Serious events: 22 serious events
Other events: 60 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1- Cohort 1 (250 mg Enzastaurin)
n=6 participants at risk
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 Cohort 2 (500 mg Enzastaurin)
n=6 participants at risk
Phase 1--Determination of the maximum tolerated dose (MTD) of enzastaurin in participants with newly diagnosed GBM or GS receiving a 500 mg dose.
|
Phase 2 - 250 mg Enzastaurin
n=60 participants at risk
Participants received 250 mg enzastaurin daily for 6 weeks, then twelve 28-day cycles.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
General disorders
Asthenia
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
General disorders
Disease progression
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
3.3%
2/60 • Number of events 2
|
|
General disorders
Fatigue
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
General disorders
Systemic leakage
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Infections and infestations
Infection
|
0.00%
0/6
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
4/60 • Number of events 4
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Injury, poisoning and procedural complications
Vascular access complication
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Nervous system disorders
Cognitive disorder
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Nervous system disorders
Complex partial seizure
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Nervous system disorders
Convulsion
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
4/60 • Number of events 4
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/6
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Nervous system disorders
Muscular weakness
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Nervous system disorders
Myelitis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Nervous system disorders
Speech disorder
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Nervous system disorders
Syncope
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/6
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Psychiatric disorders
Delirium
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Psychiatric disorders
Depression
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/6
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Vascular disorders
Embolism
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Vascular disorders
Pulmonary embolism
|
0.00%
0/6
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
0.00%
0/6
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
Other adverse events
| Measure |
Phase 1- Cohort 1 (250 mg Enzastaurin)
n=6 participants at risk
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 Cohort 2 (500 mg Enzastaurin)
n=6 participants at risk
Phase 1--Determination of the maximum tolerated dose (MTD) of enzastaurin in participants with newly diagnosed GBM or GS receiving a 500 mg dose.
|
Phase 2 - 250 mg Enzastaurin
n=60 participants at risk
Participants received 250 mg enzastaurin daily for 6 weeks, then twelve 28-day cycles.
|
|---|---|---|---|
|
Investigations
Alkaline phosphatase increased
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
5.0%
3/60 • Number of events 3
|
|
Investigations
Aspartate aminotransferase increased
|
50.0%
3/6 • Number of events 3
|
33.3%
2/6 • Number of events 2
|
16.7%
10/60 • Number of events 10
|
|
Investigations
Creatinine increased
|
33.3%
2/6 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
10.0%
6/60 • Number of events 6
|
|
Investigations
Ear, nose and throat examination abnormal
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Investigations
Hemoglobin
|
50.0%
3/6 • Number of events 3
|
16.7%
1/6 • Number of events 1
|
48.3%
29/60 • Number of events 29
|
|
Investigations
Hemoglobin decreased
|
33.3%
2/6 • Number of events 2
|
50.0%
3/6 • Number of events 3
|
21.7%
13/60 • Number of events 13
|
|
Investigations
International normalized ratio
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Investigations
Leukocyte count decreased
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
50.0%
30/60 • Number of events 30
|
|
Investigations
Neutrophil count decreased
|
33.3%
2/6 • Number of events 2
|
50.0%
3/6 • Number of events 3
|
11.7%
7/60 • Number of events 7
|
|
Investigations
Neutrophils
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
18.3%
11/60 • Number of events 11
|
|
Investigations
Platelet count decreased
|
83.3%
5/6 • Number of events 5
|
50.0%
3/6 • Number of events 3
|
20.0%
12/60 • Number of events 12
|
|
Investigations
Platelets decreased
|
33.3%
2/6 • Number of events 2
|
50.0%
3/6 • Number of events 3
|
38.3%
23/60 • Number of events 23
|
|
Investigations
Proctoscopy abnormal
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Investigations
Weight gain
|
50.0%
3/6 • Number of events 3
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
Investigations
Weight loss
|
33.3%
2/6 • Number of events 2
|
50.0%
3/6 • Number of events 3
|
13.3%
8/60 • Number of events 8
|
|
Metabolism and nutrition disorders
Anorexia
|
66.7%
4/6 • Number of events 4
|
50.0%
3/6 • Number of events 3
|
43.3%
26/60 • Number of events 26
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary disorder
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
4/60 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Acne
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
68.3%
41/60 • Number of events 41
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
6.7%
4/60 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Skin and subcutaneous tissue disorders
Petechiae
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
4/60 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
8.3%
5/60 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
13.3%
8/60 • Number of events 8
|
|
Skin and subcutaneous tissue disorders
Rash desquamating
|
50.0%
3/6 • Number of events 3
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
6.7%
4/60 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Sweating
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
5.0%
3/60 • Number of events 3
|
|
Vascular disorders
Phlebitis superficial
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Vascular disorders
Thrombosis
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
0.00%
0/60
|
|
Vascular disorders
Vascular disorder
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
0.00%
0/60
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypercholesterolemia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
83.3%
5/6 • Number of events 5
|
16.7%
1/6 • Number of events 1
|
63.3%
38/60 • Number of events 39
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
10.0%
6/60 • Number of events 6
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
0.00%
0/6
|
0.00%
0/6
|
6.7%
4/60 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypernatremia
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
15.0%
9/60 • Number of events 9
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
20.0%
12/60 • Number of events 12
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
21.7%
13/60 • Number of events 13
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
50.0%
3/6 • Number of events 3
|
16.7%
1/6 • Number of events 1
|
13.3%
8/60 • Number of events 8
|
|
Metabolism and nutrition disorders
Hypokalemia
|
16.7%
1/6 • Number of events 1
|
50.0%
3/6 • Number of events 3
|
21.7%
13/60 • Number of events 13
|
|
Metabolism and nutrition disorders
Hyponatremia
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
20.0%
12/60 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
66.7%
4/6 • Number of events 4
|
16.7%
1/6 • Number of events 1
|
10.0%
6/60 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Joint disorder
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
6.7%
4/60 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Joint pain
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
6.7%
4/60 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness
|
0.00%
0/6
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
6.7%
4/60 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/6
|
0.00%
0/6
|
21.7%
13/60 • Number of events 13
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
6.7%
4/60 • Number of events 4
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Nervous system disorders
Ataxia
|
16.7%
1/6 • Number of events 1
|
50.0%
3/6 • Number of events 3
|
8.3%
5/60 • Number of events 5
|
|
Nervous system disorders
Central nervous system necrosis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Nervous system disorders
Cognitive disturbance
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
11.7%
7/60 • Number of events 7
|
|
Nervous system disorders
Convulsion
|
33.3%
2/6 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
6.7%
4/60 • Number of events 4
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
5.0%
3/60 • Number of events 3
|
|
Nervous system disorders
Dizziness
|
33.3%
2/6 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
11.7%
7/60 • Number of events 7
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • Number of events 2
|
50.0%
3/6 • Number of events 3
|
48.3%
29/60 • Number of events 29
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Nervous system disorders
Memory impairment
|
66.7%
4/6 • Number of events 4
|
33.3%
2/6 • Number of events 2
|
33.3%
20/60 • Number of events 20
|
|
Nervous system disorders
Neurologic disorder NOS
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Nervous system disorders
Peripheral motor neuropathy
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
18.3%
11/60 • Number of events 11
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
33.3%
2/6 • Number of events 2
|
50.0%
3/6 • Number of events 3
|
15.0%
9/60 • Number of events 9
|
|
Nervous system disorders
Speech disorder
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
18.3%
11/60 • Number of events 11
|
|
Nervous system disorders
Taste alteration
|
50.0%
3/6 • Number of events 3
|
0.00%
0/6
|
20.0%
12/60 • Number of events 12
|
|
Nervous system disorders
Tremor
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
10.0%
6/60 • Number of events 6
|
|
Nervous system disorders
Visual field defect
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
33.3%
2/6 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
18.3%
11/60 • Number of events 11
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
16.7%
10/60 • Number of events 10
|
|
Psychiatric disorders
Depression
|
33.3%
2/6 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
23.3%
14/60 • Number of events 14
|
|
Psychiatric disorders
Insomnia
|
16.7%
1/6 • Number of events 1
|
50.0%
3/6 • Number of events 3
|
33.3%
20/60 • Number of events 20
|
|
Psychiatric disorders
Libido decreased
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Renal and urinary disorders
Urinary frequency
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
8.3%
5/60 • Number of events 5
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
3.3%
2/60 • Number of events 2
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
|
Renal and urinary disorders
Urine discoloration
|
66.7%
4/6 • Number of events 4
|
66.7%
4/6 • Number of events 4
|
13.3%
8/60 • Number of events 8
|
|
Renal and urinary disorders
Urogenital disorder
|
0.00%
0/6
|
0.00%
0/6
|
5.0%
3/60 • Number of events 4
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Reproductive system and breast disorders
Reproductive tract disorder
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Reproductive system and breast disorders
Uterine pain
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
13.3%
8/60 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/6
|
0.00%
0/6
|
8.3%
5/60 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
Hemorrhage nasal
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
5.0%
3/60 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Gastrointestinal disorders
Hemorrhoids
|
0.00%
0/6
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
100.0%
6/6 • Number of events 6
|
66.7%
4/6 • Number of events 4
|
56.7%
34/60 • Number of events 34
|
|
Gastrointestinal disorders
Oral hemorrhage
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Infections and infestations
Bladder infection
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Infections and infestations
Bone infection
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Infections and infestations
Infection
|
33.3%
2/6 • Number of events 2
|
16.7%
1/6 • Number of events 1
|
5.0%
3/60 • Number of events 3
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
8.3%
5/60 • Number of events 5
|
|
Infections and infestations
Rhinitis
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
0.00%
0/60
|
|
Infections and infestations
Sinusitis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
8.3%
5/60 • Number of events 5
|
|
Infections and infestations
Upper respiratory infection
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
5.0%
3/60 • Number of events 3
|
|
Infections and infestations
Wound infection
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Injury, poisoning and procedural complications
Radiation recall reaction (dermatologic)
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
15.0%
9/60 • Number of events 9
|
|
Injury, poisoning and procedural complications
Wound complication
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Investigations
Alanine aminotransferase increased
|
66.7%
4/6 • Number of events 4
|
33.3%
2/6 • Number of events 2
|
23.3%
14/60 • Number of events 14
|
|
Gastrointestinal disorders
Oral pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Gastrointestinal disorders
Periodontal disease
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Gastrointestinal disorders
Toothache
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Gastrointestinal disorders
Vomiting
|
66.7%
4/6 • Number of events 4
|
16.7%
1/6 • Number of events 1
|
23.3%
14/60 • Number of events 14
|
|
General disorders
Calcinosis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
General disorders
Chills
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
|
General disorders
Edema
|
0.00%
0/6
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
General disorders
Edema limbs
|
0.00%
0/6
|
0.00%
0/6
|
8.3%
5/60 • Number of events 5
|
|
General disorders
Facial pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
General disorders
Fatigue
|
100.0%
6/6 • Number of events 6
|
100.0%
6/6 • Number of events 6
|
86.7%
52/60 • Number of events 52
|
|
General disorders
Fever
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
3.3%
2/60 • Number of events 2
|
|
General disorders
Flu-like illness
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
General disorders
Flu-like symptoms
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
|
General disorders
Pain
|
0.00%
0/6
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
Hepatobiliary disorders
Hyperbilirubinemia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
21.7%
13/60 • Number of events 14
|
|
Immune system disorders
Allergic reaction
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
6.7%
4/60 • Number of events 4
|
|
Blood and lymphatic system disorders
Leukopenia
|
66.7%
4/6 • Number of events 4
|
66.7%
4/6 • Number of events 4
|
26.7%
16/60 • Number of events 16
|
|
Blood and lymphatic system disorders
Lymphopenia
|
83.3%
5/6 • Number of events 5
|
100.0%
6/6 • Number of events 6
|
86.7%
52/60 • Number of events 52
|
|
Cardiac disorders
Cardiac disorder
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Ear and labyrinth disorders
Auditory disorder
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Ear and labyrinth disorders
Ear pain
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Ear and labyrinth disorders
Hearing loss
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/6
|
0.00%
0/6
|
8.3%
5/60 • Number of events 5
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/6
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
Endocrine disorders
Cushingoid
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
5.0%
3/60 • Number of events 3
|
|
Eye disorders
Diplopia
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/60
|
|
Eye disorders
Vision blurred
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
3.3%
2/60 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
1.7%
1/60 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
3.3%
2/60 • Number of events 2
|
|
Gastrointestinal disorders
Anal hemorrhage
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Gastrointestinal disorders
Constipation
|
100.0%
6/6 • Number of events 6
|
66.7%
4/6 • Number of events 4
|
70.0%
42/60 • Number of events 42
|
|
Gastrointestinal disorders
Diarrhea
|
66.7%
4/6 • Number of events 4
|
33.3%
2/6 • Number of events 2
|
15.0%
9/60 • Number of events 9
|
|
Gastrointestinal disorders
Dyspepsia
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
8.3%
5/60 • Number of events 5
|
|
Gastrointestinal disorders
Feces discolored
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Gastrointestinal disorders
Flatulence
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
0.00%
0/60
|
|
Gastrointestinal disorders
Gastritis
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
1.7%
1/60 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60