Trial Outcomes & Findings for PRELUDE:Study to Investigate the Prevention of Relapse in Lymphoma Using Daily Enzastaurin (NCT NCT00332202)
NCT ID: NCT00332202
Last Updated: 2018-09-10
Results Overview
Overall Disease-Free Survival (DFS) time is defined as the time from the date of study enrollment to the first date of objectively determined disease recurrence (progressive disease) or death from any cause. DFS was assessed according to International Working Group recommendations. Progressive disease (PD) is defined as a ≥ 50% increase from the lowest point in the sum of the product of the diameters (SPD) of any previously identified abnormal node for partial or nonresponders, or the appearance of any new lesion during or at the end of therapy.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
758 participants
Primary outcome timeframe
Baseline to Measured Progressive Disease or Death from Any Cause (up to 80.30 months)
Results posted on
2018-09-10
Participant Flow
Participant milestones
| Measure |
Enzastaurin: Arm A - Experimental
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
|---|---|---|
|
Overall Study
STARTED
|
504
|
254
|
|
Overall Study
Received At Least One Dose of Study Drug
|
493
|
249
|
|
Overall Study
COMPLETED
|
263
|
129
|
|
Overall Study
NOT COMPLETED
|
241
|
125
|
Reasons for withdrawal
| Measure |
Enzastaurin: Arm A - Experimental
Enzastaurin 500 milligram (mg) administered orally (PO) each day (QD) after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
|---|---|---|
|
Overall Study
Adverse Event
|
72
|
28
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Physician Decision
|
6
|
8
|
|
Overall Study
Protocol Entry Criteria Not Met
|
6
|
5
|
|
Overall Study
Protocol Violation
|
7
|
2
|
|
Overall Study
Sponsor Decision
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
36
|
17
|
|
Overall Study
Progressive Disease
|
106
|
60
|
|
Overall Study
Death
|
5
|
2
|
Baseline Characteristics
PRELUDE:Study to Investigate the Prevention of Relapse in Lymphoma Using Daily Enzastaurin
Baseline characteristics by cohort
| Measure |
Enzastaurin: Arm A - Experimental
n=504 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=254 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Total
n=758 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.19 Years
STANDARD_DEVIATION 13.13 • n=93 Participants
|
62.65 Years
STANDARD_DEVIATION 12.09 • n=4 Participants
|
62.35 Years
STANDARD_DEVIATION 12.78 • n=27 Participants
|
|
Sex: Female, Male
Female
|
245 Participants
n=93 Participants
|
105 Participants
n=4 Participants
|
350 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
259 Participants
n=93 Participants
|
149 Participants
n=4 Participants
|
408 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
African
|
5 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
309 Participants
n=93 Participants
|
155 Participants
n=4 Participants
|
464 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
144 Participants
n=93 Participants
|
73 Participants
n=4 Participants
|
217 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
24 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
37 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Native American
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
West Asian (Indian sub-continent)
|
21 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
|
Region of Enrollment
Australia
|
20 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
29 Participants
n=27 Participants
|
|
Region of Enrollment
Belgium
|
10 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
|
Region of Enrollment
Brazil
|
13 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
|
Region of Enrollment
Canada
|
24 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
|
Region of Enrollment
China
|
18 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
|
Region of Enrollment
Czechia
|
6 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Region of Enrollment
Germany
|
15 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
|
Region of Enrollment
Denmark
|
9 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
|
Region of Enrollment
Spain
|
20 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
|
Region of Enrollment
Finland
|
11 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Region of Enrollment
France
|
22 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
|
Region of Enrollment
Greece
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Region of Enrollment
Hungary
|
4 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Region of Enrollment
India
|
22 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
33 Participants
n=27 Participants
|
|
Region of Enrollment
Italy
|
15 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
|
Region of Enrollment
Japan
|
54 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
87 Participants
n=27 Participants
|
|
Region of Enrollment
South Korea
|
37 Participants
n=93 Participants
|
21 Participants
n=4 Participants
|
58 Participants
n=27 Participants
|
|
Region of Enrollment
Mexico
|
13 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
|
Region of Enrollment
Poland
|
9 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
|
Region of Enrollment
Puerto Rico
|
3 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Region of Enrollment
Portugal
|
5 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Region of Enrollment
Sweden
|
19 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
|
Region of Enrollment
Taiwan
|
24 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
|
Region of Enrollment
United Kingdom
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
125 Participants
n=93 Participants
|
61 Participants
n=4 Participants
|
186 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline to Measured Progressive Disease or Death from Any Cause (up to 80.30 months)Population: All randomized participants. DFS is censored at the last assessable disease free assessment for participants who are alive or have not progressed. The number of censored participant data for enzastaurin and placebo is 369 (73.2%) and 180 (70.9%), respectively.
Overall Disease-Free Survival (DFS) time is defined as the time from the date of study enrollment to the first date of objectively determined disease recurrence (progressive disease) or death from any cause. DFS was assessed according to International Working Group recommendations. Progressive disease (PD) is defined as a ≥ 50% increase from the lowest point in the sum of the product of the diameters (SPD) of any previously identified abnormal node for partial or nonresponders, or the appearance of any new lesion during or at the end of therapy.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=504 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=254 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Overall Disease-Free Survival
|
42.8 Month
Interval 0.03 to 76.81
|
43.1 Month
Interval 0.03 to 80.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to 2 YearsPopulation: All randomized participants.
Disease-free survival at 2 years (DFS2) is defined as the rate of DFS at 2 years from the date of study enrollment and is determined using the distribution of overall DFS times. Disease-free survival rates at 2 years will be estimated using the Kaplan-Meier method.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=504 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=254 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Disease Free Survival at 2 Years
|
0.785 proportion of participants
Interval 0.745 to 0.819
|
0.748 proportion of participants
Interval 0.687 to 0.798
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Objective PD, Start of New Therapy or Death From Any Cause (up to 76.81 months)Population: All randomized participants. EFS is censored at the last assessable disease-free assessment for participants who are alive, have not progressed or started new anticancer treatment. The number of censored participant data for enzastaurin and placebo is 364 (72.2%) and 176 (69.3%), respectively.
Overall Event-Free Survival (EFS) time is defined as the time from the date of study enrollment to the first date of objectively determined disease recurrence (progressive disease), institution of a new anti-cancer treatment, or death from any cause. Progressive disease (PD) is defined as a ≥ 50% increase from the lowest point in the sum of the product of the diameters (SPD) of any previously identified abnormal node for partial or nonresponders, or the appearance of any new lesion during or at the end of therapy.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=504 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=254 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Event-Free Survival
Minimum EFS Survival
|
0.03 Month
|
0.03 Month
|
—
|
—
|
|
Event-Free Survival
Maximum EFS Survival
|
76.81 Month
|
71.56 Month
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to 2 YearsPopulation: All randomized participants.
Event-Free Survival at 2 years (EFS2) is defined as the rate of EFS at 2 years from the date of study enrollment and is determined using the distribution of overall EFS times. Event-free survival rates at 2 years will be estimated using the Kaplan-Meier method.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=504 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=254 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Event-Free Survival at 2 Years
|
0.781 Proportion of participants
Interval 0.741 to 0.816
|
0.734 Proportion of participants
Interval 0.673 to 0.785
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Date of Death from Any Cause (up to 80.30 months)Population: All randomized participants. Overall survival is censored at the last date of contact for participants who have no reported death. The number of censored participant data for enzastaurin and placebo is 404 (80.2%) and 205 (80.7%), respectively.
Overall survival (OS) time is defined as the time from the date of study enrollment to the date of death from any cause.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=504 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=254 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Overall Survival
Minimum OS Survival
|
0.03 Month
|
0.03 Month
|
—
|
—
|
|
Overall Survival
Maximum OS Survival
|
76.81 Month
|
80.30 Month
|
—
|
—
|
SECONDARY outcome
Timeframe: First dose through 30 days post-study treatment discontinuation (up to 81.30 months)Population: All randomized participants who received at least one dose of study drug.
Number of participants with treatment-emergent adverse events.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=493 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=249 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events
|
459 Participants
|
230 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Month 2; Baseline, Month 4; Baseline, Month 6; Baseline, Month 12; Baseline, Month 18; Baseline, Month 24; Baseline, Month 36Population: All randomized participants who completed at least one FACT-Lym assessment.
The FACT-Lym assesses health-related quality of life (HRQoL) in participants with non-Hodgkin lymphoma. It includes the 27-item cancer-specific FACT-G (General), which assesses physical, social/family, emotional and functional well-being, plus a 15-item subscale that assesses concerns specific to lymphoma. Each item is scored on a scale from 0 (not at all) to 4 (very much), yielding a possible score of 0-168, with higher scores representing better HRQoL. This analysis utilized mixed-effect model repeated measure (MMRM) analysis of change from baseline adjusting for baseline covariates.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=348 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=189 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Quality of Life: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score
Month 2
|
2.45 Units on a Scale
Standard Error 0.67
|
1.86 Units on a Scale
Standard Error 0.93
|
—
|
—
|
|
Quality of Life: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score
Month 6
|
2.04 Units on a Scale
Standard Error 0.87
|
2.82 Units on a Scale
Standard Error 1.10
|
—
|
—
|
|
Quality of Life: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score
Month 12
|
3.85 Units on a Scale
Standard Error 0.87
|
2.11 Units on a Scale
Standard Error 1.29
|
—
|
—
|
|
Quality of Life: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score
Month 4
|
2.56 Units on a Scale
Standard Error 0.80
|
2.51 Units on a Scale
Standard Error 1.06
|
—
|
—
|
|
Quality of Life: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score
Month 18
|
2.87 Units on a Scale
Standard Error 0.89
|
1.73 Units on a Scale
Standard Error 1.26
|
—
|
—
|
|
Quality of Life: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score
Month 24
|
2.72 Units on a Scale
Standard Error 0.99
|
3.96 Units on a Scale
Standard Error 1.26
|
—
|
—
|
|
Quality of Life: Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Score
Month 36
|
2.54 Units on a Scale
Standard Error 1.13
|
4.22 Units on a Scale
Standard Error 1.43
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Month 6; Baseline, Month 24; Baseline, Month 33Population: All randomized participants who completed at least one EQ-5D assessment.
The EQ-5D instrument is a participant-rated questionnaire used to evaluate health status. The EQ-5D assesses five dimensions (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression) that participants rate using three levels (no problem, some problem, or extreme problem), as well as overall health status. The five dimensions can be combined using country-specific weights to create an estimate of overall health status score. The possible values for score range from -0.594 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 1 represents the best possible health state. This analysis utilized mixed-effect model repeated measure (MMRM) analysis of change from baseline in the EQ-5D for the United Kingdom population-based index score adjusting for baseline covariates.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=346 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=187 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Change From Baseline in EuroQol-5D (EQ-5D) Score
Month 6
|
0.02 Units on a Scale
Standard Error 0.01
|
0.00 Units on a Scale
Standard Error 0.01
|
—
|
—
|
|
Change From Baseline in EuroQol-5D (EQ-5D) Score
Month 24
|
0.02 Units on a Scale
Standard Error 0.01
|
0.03 Units on a Scale
Standard Error 0.02
|
—
|
—
|
|
Change From Baseline in EuroQol-5D (EQ-5D) Score
Month 33
|
0.03 Units on a Scale
Standard Error 0.01
|
0.03 Units on a Scale
Standard Error 0.01
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to 24 months (2 years)Population: All randomized participants for which a pre-treatment tumor tissue was provided and had evaluable samples.
Reported are the DFS for GCB and non-GCB status. DLBCL molecular subtypes of GCB/non-GCB using Hans' algorithm were determined by protein expression by immunohistochemistry (IHC) staining was used to assess molecular subtype characterization of GCB and non-GCB.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=79 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=63 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
n=30 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
n=39 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Translational Research: DFS Participants With Diffuse Large B-cell Lymphoma (DLBCL) Germinal-center B-cells (GCB) Versus Non-germinal-center B-cells
|
76.31 percentage of participants
Interval 65.1 to 84.4
|
75.97 percentage of participants
Interval 63.3 to 84.8
|
66.21 percentage of participants
Interval 46.3 to 80.2
|
68.20 percentage of participants
Interval 50.7 to 80.6
|
SECONDARY outcome
Timeframe: Baseline to 94.5 monthsPopulation: All randomized participants for which a pre-treatment tumor tissue was provided and had evaluable samples.
Reported are the DFS based on PKC-β2 protein expression. Immunohistochemistry (IHC) staining was performed to assess protein expression of PKC-β2 in cytoplasm scored for percent of tumor cells stained, and using 50% positive staining as the cutoff for high/low expression (high expression: \>=50% staining, low expression: \<50% staining).
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=39 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
n=117 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
n=21 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
n=50 Participants
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Translational Research: DFS of Participants With Diffuse Large B-cell Lymphoma (DLBCL) Protein Kinase C-β2 (PKC-β2) Expression
|
64.86 percentage of participants
Interval 47.3 to 77.9
|
81.16 percentage of participants
Interval 72.6 to 87.3
|
61.54 percentage of participants
Interval 37.6 to 78.6
|
70.58 percentage of participants
Interval 55.3 to 81.5
|
SECONDARY outcome
Timeframe: Month 2, Month 4: PredosePopulation: All participants who received at least one dose of the study drug and had evaluable PK data.
Outcome measures
| Measure |
Enzastaurin: Arm A - Experimental
n=328 Participants
Enzastaurin 500 mg administered PO QD after an initial loading dose of 1125 mg on Day 1.
|
Placebo: Arm B - Control
Placebo administered PO QD after an initial loading dose of placebo on Day 1.
|
Placebo: Arm B - Control With Germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1.Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
Placebo Arm B- Control With Non-germinal-center B-cells
Placebo administered PO QD after an initial loading dose of placebo on Day 1. Participants from the placebo treatment group with diffuse large B-cell lymphoma expression profile not similar to germinal-center B-cells.
|
|---|---|---|---|---|
|
Pharmacokinetics: Average Steady-State Concentration (Cavg,ss) for Total Analyte
|
2370 nanomole/liter (nmol/L)
Geometric Coefficient of Variation 59.9
|
—
|
—
|
—
|
Adverse Events
Enzastaurin: Arm A - Experimental
Serious events: 135 serious events
Other events: 406 other events
Deaths: 0 deaths
Placebo: Arm B - Control
Serious events: 72 serious events
Other events: 185 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Enzastaurin: Arm A - Experimental
n=493 participants at risk
Administered orally as four 125-mg tablets daily (after an initial loading dose of three 125-mg tablets given three times on Day 1)
|
Placebo: Arm B - Control
n=249 participants at risk
Administered orally as four tablets daily (after an initial loading dose of three tablets given three times on Day 1)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.0%
5/493 • Number of events 9
|
0.00%
0/249
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.2%
6/493 • Number of events 6
|
1.2%
3/249 • Number of events 4
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.20%
1/493 • Number of events 1
|
0.40%
1/249 • Number of events 1
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.61%
3/493 • Number of events 3
|
0.80%
2/249 • Number of events 2
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Cardiac disorders
Angina pectoris
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Cardiac disorders
Angina unstable
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Cardiac disorders
Arrhythmia
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/493
|
0.80%
2/249 • Number of events 15
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Cardiac disorders
Atrioventricular block complete
|
0.20%
1/493 • Number of events 11
|
0.40%
1/249 • Number of events 1
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Cardiac disorders
Cardiac arrest
|
0.41%
2/493 • Number of events 2
|
0.40%
1/249 • Number of events 3
|
|
Cardiac disorders
Cardiac failure
|
0.61%
3/493 • Number of events 16
|
0.80%
2/249 • Number of events 2
|
|
Cardiac disorders
Cardiac failure chronic
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Cardiac disorders
Cardiac failure congestive
|
0.20%
1/493 • Number of events 2
|
0.80%
2/249 • Number of events 4
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Cardiac disorders
Cardiomyopathy
|
0.61%
3/493 • Number of events 25
|
0.00%
0/249
|
|
Cardiac disorders
Coronary artery disease
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.20%
1/493 • Number of events 6
|
0.40%
1/249 • Number of events 1
|
|
Cardiac disorders
Myocardial infarction
|
0.20%
1/493 • Number of events 1
|
0.40%
1/249 • Number of events 1
|
|
Cardiac disorders
Myocardial ischaemia
|
0.20%
1/493 • Number of events 1
|
0.40%
1/249 • Number of events 3
|
|
Cardiac disorders
Sick sinus syndrome
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Cardiac disorders
Sinus bradycardia
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Cardiac disorders
Torsade de pointes
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Cardiac disorders
Ventricular fibrillation
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Ear and labyrinth disorders
Vertigo
|
0.20%
1/493 • Number of events 8
|
0.00%
0/249
|
|
Eye disorders
Cataract
|
0.41%
2/493 • Number of events 4
|
0.80%
2/249 • Number of events 2
|
|
Eye disorders
Conjunctival haemorrhage
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Eye disorders
Eyelid ptosis
|
0.20%
1/493 • Number of events 5
|
0.40%
1/249 • Number of events 6
|
|
Eye disorders
Ophthalmoplegia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Eye disorders
Retinal detachment
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Eye disorders
Retinal vein occlusion
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Eye disorders
Vision blurred
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Gastrointestinal disorders
Anal prolapse
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Gastrointestinal disorders
Colitis
|
0.20%
1/493 • Number of events 1
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Colonic polyp
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Gastrointestinal disorders
Constipation
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Gastrointestinal disorders
Diarrhoea
|
0.61%
3/493 • Number of events 3
|
0.00%
0/249
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/493
|
0.80%
2/249 • Number of events 17
|
|
Gastrointestinal disorders
Food poisoning
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Gastritis
|
0.20%
1/493 • Number of events 13
|
0.00%
0/249
|
|
Gastrointestinal disorders
Gastrointestinal obstruction
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Gingivitis ulcerative
|
0.20%
1/493 • Number of events 3
|
0.00%
0/249
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.41%
2/493 • Number of events 3
|
0.00%
0/249
|
|
Gastrointestinal disorders
Ileus
|
0.41%
2/493 • Number of events 3
|
0.00%
0/249
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.41%
2/493 • Number of events 2
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Jejunal perforation
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Gastrointestinal disorders
Nausea
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Gastrointestinal disorders
Oral lichen planus
|
0.20%
1/493 • Number of events 11
|
0.00%
0/249
|
|
Gastrointestinal disorders
Pancreatitis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.20%
1/493 • Number of events 2
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Pseudopolyposis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.20%
1/493 • Number of events 2
|
0.40%
1/249 • Number of events 2
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Gastrointestinal disorders
Volvulus of small bowel
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Gastrointestinal disorders
Vomiting
|
0.41%
2/493 • Number of events 2
|
0.40%
1/249 • Number of events 15
|
|
General disorders
Asthenia
|
0.41%
2/493 • Number of events 4
|
0.40%
1/249 • Number of events 2
|
|
General disorders
Chest pain
|
0.41%
2/493 • Number of events 2
|
0.40%
1/249 • Number of events 1
|
|
General disorders
Death
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
General disorders
General physical health deterioration
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
General disorders
Multi-organ disorder
|
0.00%
0/493
|
0.40%
1/249 • Number of events 3
|
|
General disorders
Multi-organ failure
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
General disorders
Pain
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
General disorders
Spinal pain
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Hepatobiliary disorders
Cholecystitis
|
0.61%
3/493 • Number of events 4
|
0.00%
0/249
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.81%
4/493 • Number of events 6
|
0.00%
0/249
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.20%
1/493 • Number of events 7
|
0.00%
0/249
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Immune system disorders
Allergy to arthropod sting
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Immune system disorders
Contrast media allergy
|
0.00%
0/493
|
0.80%
2/249 • Number of events 2
|
|
Infections and infestations
Abdominal sepsis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Arthritis infective
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Beta haemolytic streptococcal infection
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Bronchitis
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Bronchopulmonary aspergillosis
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Infections and infestations
Cellulitis
|
0.41%
2/493 • Number of events 3
|
0.00%
0/249
|
|
Infections and infestations
Cervicitis
|
0.42%
1/239 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Clostridium difficile colitis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Enteritis infectious
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Enterocolitis infectious
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Escherichia sepsis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Gastroenteritis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Helicobacter gastritis
|
0.00%
0/493
|
0.80%
2/249 • Number of events 3
|
|
Infections and infestations
Hepatic cyst infection
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Infections and infestations
Hepatitis b
|
0.00%
0/493
|
1.2%
3/249 • Number of events 11
|
|
Infections and infestations
Hepatitis c
|
0.20%
1/493 • Number of events 7
|
0.00%
0/249
|
|
Infections and infestations
Herpes zoster
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Infection
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Infectious peritonitis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Intervertebral discitis
|
0.20%
1/493 • Number of events 11
|
0.00%
0/249
|
|
Infections and infestations
Lobar pneumonia
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Infections and infestations
Lung infection
|
0.41%
2/493 • Number of events 2
|
0.00%
0/249
|
|
Infections and infestations
Myelitis
|
0.00%
0/493
|
0.40%
1/249 • Number of events 10
|
|
Infections and infestations
Necrotising fasciitis
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Neutropenic infection
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Periodontitis
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Infections and infestations
Pneumonia
|
1.2%
6/493 • Number of events 7
|
2.8%
7/249 • Number of events 10
|
|
Infections and infestations
Pseudomembranous colitis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Pseudomonal bacteraemia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Pyelonephritis
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Infections and infestations
Scrub typhus
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Sepsis
|
1.0%
5/493 • Number of events 7
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Septic shock
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.61%
3/493 • Number of events 5
|
0.00%
0/249
|
|
Infections and infestations
Urosepsis
|
0.41%
2/493 • Number of events 3
|
0.00%
0/249
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Infections and infestations
Wound infection
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Injury, poisoning and procedural complications
Acetabulum fracture
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Injury, poisoning and procedural complications
Cervical vertebral fracture
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Injury, poisoning and procedural complications
Concussion
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/493
|
0.80%
2/249 • Number of events 3
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.20%
1/493 • Number of events 12
|
0.40%
1/249 • Number of events 1
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Injury, poisoning and procedural complications
Maternal exposure during pregnancy
|
0.84%
2/239 • Number of events 8
|
0.00%
0/249
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.20%
1/493 • Number of events 7
|
0.40%
1/249 • Number of events 17
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/493
|
0.40%
1/249 • Number of events 10
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.20%
1/493 • Number of events 6
|
0.00%
0/249
|
|
Investigations
Aspartate aminotransferase increased
|
0.20%
1/493 • Number of events 3
|
0.00%
0/249
|
|
Investigations
Ejection fraction decreased
|
0.20%
1/493 • Number of events 1
|
0.40%
1/249 • Number of events 3
|
|
Investigations
Electrocardiogram abnormal
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Investigations
Electrocardiogram qt prolonged
|
0.61%
3/493 • Number of events 12
|
0.40%
1/249 • Number of events 2
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Metabolism and nutrition disorders
Dehydration
|
0.20%
1/493 • Number of events 1
|
0.40%
1/249 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.41%
2/493 • Number of events 2
|
0.00%
0/249
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.41%
2/493 • Number of events 2
|
0.80%
2/249 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Haemarthrosis
|
0.20%
1/493 • Number of events 6
|
0.00%
0/249
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/493
|
0.40%
1/249 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.20%
1/493 • Number of events 1
|
0.80%
2/249 • Number of events 21
|
|
Musculoskeletal and connective tissue disorders
Osteolysis
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.20%
1/493 • Number of events 11
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebellar tumour
|
0.20%
1/493 • Number of events 3
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.20%
1/493 • Number of events 9
|
0.40%
1/249 • Number of events 14
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Diffuse large b-cell lymphoma
|
0.00%
0/493
|
0.40%
1/249 • Number of events 3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.41%
2/493 • Number of events 4
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer metastatic
|
0.20%
1/493 • Number of events 9
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hypopharyngeal cancer
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large intestine carcinoma
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm
|
0.00%
0/493
|
0.40%
1/249 • Number of events 10
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.41%
2/493 • Number of events 7
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma
|
0.20%
1/493 • Number of events 6
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
0.00%
0/493
|
0.40%
1/249 • Number of events 3
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian neoplasm
|
0.42%
1/239 • Number of events 1
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neoplasm
|
0.20%
1/493 • Number of events 5
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.39%
1/254 • Number of events 5
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.20%
1/493 • Number of events 9
|
0.40%
1/249 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Salivary gland adenoma
|
0.20%
1/493 • Number of events 4
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.20%
1/493 • Number of events 18
|
0.00%
0/249
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid neoplasm
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Nervous system disorders
Basal ganglia infarction
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.41%
2/493 • Number of events 2
|
0.00%
0/249
|
|
Nervous system disorders
Convulsion
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Nervous system disorders
Cranial nerve paralysis
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 6
|
|
Nervous system disorders
Epilepsy
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Nervous system disorders
Grand mal convulsion
|
0.41%
2/493 • Number of events 2
|
0.00%
0/249
|
|
Nervous system disorders
Headache
|
0.20%
1/493 • Number of events 1
|
0.40%
1/249 • Number of events 15
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/493
|
0.40%
1/249 • Number of events 15
|
|
Nervous system disorders
Hypoxic-ischaemic encephalopathy
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Nervous system disorders
Ischaemic stroke
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Nervous system disorders
Nerve root compression
|
0.20%
1/493 • Number of events 4
|
0.00%
0/249
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/493
|
0.40%
1/249 • Number of events 9
|
|
Nervous system disorders
Posterior reversible encephalopathy syndrome
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Nervous system disorders
Sciatica
|
0.20%
1/493 • Number of events 3
|
0.40%
1/249 • Number of events 3
|
|
Nervous system disorders
Syncope
|
1.2%
6/493 • Number of events 8
|
0.00%
0/249
|
|
Nervous system disorders
Tongue paralysis
|
0.00%
0/493
|
0.40%
1/249 • Number of events 15
|
|
Nervous system disorders
Tonic convulsion
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/493
|
0.80%
2/249 • Number of events 3
|
|
Nervous system disorders
Vith nerve paralysis
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Nervous system disorders
Vocal cord paralysis
|
0.00%
0/493
|
0.40%
1/249 • Number of events 2
|
|
Psychiatric disorders
Delirium
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Psychiatric disorders
Depression
|
0.20%
1/493 • Number of events 14
|
0.00%
0/249
|
|
Renal and urinary disorders
Calculus ureteric
|
0.20%
1/493 • Number of events 6
|
0.00%
0/249
|
|
Renal and urinary disorders
Hydronephrosis
|
0.20%
1/493 • Number of events 3
|
0.00%
0/249
|
|
Renal and urinary disorders
Incontinence
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Renal and urinary disorders
Oliguria
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Renal and urinary disorders
Renal failure
|
0.41%
2/493 • Number of events 4
|
0.40%
1/249 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
0.41%
2/493 • Number of events 2
|
0.00%
0/249
|
|
Renal and urinary disorders
Renal pain
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Reproductive system and breast disorders
Prostatic obstruction
|
0.39%
1/254 • Number of events 12
|
0.00%
0/249
|
|
Reproductive system and breast disorders
Prostatitis
|
0.39%
1/254 • Number of events 1
|
0.00%
0/249
|
|
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
|
0.00%
0/493
|
0.40%
1/249 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.41%
2/493 • Number of events 4
|
0.40%
1/249 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.20%
1/493 • Number of events 8
|
0.00%
0/249
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.61%
3/493 • Number of events 4
|
0.00%
0/249
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.20%
1/493 • Number of events 5
|
0.00%
0/249
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.6%
8/493 • Number of events 23
|
0.80%
2/249 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Skin and subcutaneous tissue disorders
Skin fibrosis
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.20%
1/493 • Number of events 8
|
0.00%
0/249
|
|
Surgical and medical procedures
Abdominal hernia repair
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Surgical and medical procedures
Anal fissure excision
|
0.20%
1/493 • Number of events 1
|
0.00%
0/249
|
|
Surgical and medical procedures
Meniscus removal
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
|
Surgical and medical procedures
Spinal fusion surgery
|
0.20%
1/493 • Number of events 2
|
0.00%
0/249
|
|
Vascular disorders
Aortic aneurysm
|
0.20%
1/493 • Number of events 9
|
0.00%
0/249
|
|
Vascular disorders
Deep vein thrombosis
|
0.81%
4/493 • Number of events 21
|
0.00%
0/249
|
|
Vascular disorders
Hypotension
|
0.20%
1/493 • Number of events 4
|
0.00%
0/249
|
|
Vascular disorders
Thrombosis
|
0.00%
0/493
|
0.40%
1/249 • Number of events 1
|
Other adverse events
| Measure |
Enzastaurin: Arm A - Experimental
n=493 participants at risk
Administered orally as four 125-mg tablets daily (after an initial loading dose of three 125-mg tablets given three times on Day 1)
|
Placebo: Arm B - Control
n=249 participants at risk
Administered orally as four tablets daily (after an initial loading dose of three tablets given three times on Day 1)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.7%
33/493 • Number of events 221
|
5.2%
13/249 • Number of events 79
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.5%
27/493 • Number of events 87
|
4.4%
11/249 • Number of events 45
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.5%
52/493 • Number of events 143
|
10.4%
26/249 • Number of events 66
|
|
Gastrointestinal disorders
Abdominal pain
|
8.1%
40/493 • Number of events 140
|
4.8%
12/249 • Number of events 20
|
|
Gastrointestinal disorders
Constipation
|
9.9%
49/493 • Number of events 256
|
8.0%
20/249 • Number of events 101
|
|
Gastrointestinal disorders
Diarrhoea
|
19.7%
97/493 • Number of events 387
|
13.3%
33/249 • Number of events 115
|
|
Gastrointestinal disorders
Dry mouth
|
5.1%
25/493 • Number of events 177
|
2.0%
5/249 • Number of events 44
|
|
Gastrointestinal disorders
Faeces discoloured
|
7.9%
39/493 • Number of events 340
|
0.00%
0/249
|
|
Gastrointestinal disorders
Nausea
|
14.8%
73/493 • Number of events 195
|
15.3%
38/249 • Number of events 150
|
|
Gastrointestinal disorders
Vomiting
|
9.5%
47/493 • Number of events 64
|
10.4%
26/249 • Number of events 44
|
|
General disorders
Fatigue
|
18.5%
91/493 • Number of events 628
|
18.1%
45/249 • Number of events 304
|
|
General disorders
Oedema peripheral
|
12.8%
63/493 • Number of events 370
|
6.4%
16/249 • Number of events 84
|
|
General disorders
Pyrexia
|
6.9%
34/493 • Number of events 60
|
6.4%
16/249 • Number of events 21
|
|
Infections and infestations
Nasopharyngitis
|
7.5%
37/493 • Number of events 112
|
5.2%
13/249 • Number of events 34
|
|
Infections and infestations
Upper respiratory tract infection
|
8.5%
42/493 • Number of events 80
|
6.0%
15/249 • Number of events 47
|
|
Infections and infestations
Urinary tract infection
|
5.5%
27/493 • Number of events 93
|
2.8%
7/249 • Number of events 13
|
|
Investigations
Alanine aminotransferase increased
|
5.5%
27/493 • Number of events 148
|
4.8%
12/249 • Number of events 73
|
|
Investigations
Aspartate aminotransferase increased
|
5.9%
29/493 • Number of events 191
|
4.8%
12/249 • Number of events 52
|
|
Investigations
Electrocardiogram qt prolonged
|
11.0%
54/493 • Number of events 317
|
4.4%
11/249 • Number of events 44
|
|
Investigations
Weight increased
|
4.9%
24/493 • Number of events 194
|
7.6%
19/249 • Number of events 149
|
|
Metabolism and nutrition disorders
Decreased appetite
|
6.9%
34/493 • Number of events 151
|
5.6%
14/249 • Number of events 56
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.7%
43/493 • Number of events 368
|
11.2%
28/249 • Number of events 238
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.5%
52/493 • Number of events 353
|
9.6%
24/249 • Number of events 213
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.5%
32/493 • Number of events 263
|
6.0%
15/249 • Number of events 107
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.3%
36/493 • Number of events 173
|
6.8%
17/249 • Number of events 71
|
|
Nervous system disorders
Dizziness
|
10.8%
53/493 • Number of events 238
|
8.4%
21/249 • Number of events 129
|
|
Nervous system disorders
Headache
|
9.9%
49/493 • Number of events 295
|
12.9%
32/249 • Number of events 189
|
|
Psychiatric disorders
Insomnia
|
8.1%
40/493 • Number of events 327
|
5.2%
13/249 • Number of events 107
|
|
Renal and urinary disorders
Chromaturia
|
19.5%
96/493 • Number of events 916
|
0.40%
1/249 • Number of events 13
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
15.4%
76/493 • Number of events 283
|
12.0%
30/249 • Number of events 130
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.3%
26/493 • Number of events 84
|
2.8%
7/249 • Number of events 14
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.3%
51/493 • Number of events 329
|
8.4%
21/249 • Number of events 104
|
|
Skin and subcutaneous tissue disorders
Rash
|
11.4%
56/493 • Number of events 323
|
10.8%
27/249 • Number of events 120
|
|
Vascular disorders
Hypertension
|
1.6%
8/493 • Number of events 64
|
5.2%
13/249 • Number of events 127
|
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