A Phase 2 Study With Enzastaurin Plus Chemotherapy or Placebo Plus Chemotherapy for Prostate Cancer Patients
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00466440
Collaborator
(none)
108
28
3
36
3.9
0.1
Study Details
Study Description
Brief Summary
The purpose of the study is to compare the response rates for prostate cancer patients taking chemotherapy plus enzastaurin versus chemotherapy plus placebo.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
108 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study With and Without Enzastaurin in Combination With Docetaxel and Prednisone, Followed By Enzastaurin Maintenance as First-Line Treatment in Hormone Refractory Metastatic Prostate Cancer Patients
Study Start Date
:
Jun 1, 2007
Actual Primary Completion Date
:
Aug 1, 2009
Actual Study Completion Date
:
Jun 1, 2010
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: docetaxel + prednisone + enzastaurin Regimen A: docetaxel 75 milligrams per square meter (mg/m^2), intravenous (IV) is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 milligrams (mg) oral (po), twice daily (BID) every day. In Cycle 1, enzastaurin is given as a loading dose of 1125 mg on the day prior to docetaxel and prednisone therapy, followed by enzastaurin 500 mg po, daily (QD) for the remaining Period 2 (chemotherapy) and Period 3 (maintenance). |
Drug: enzastaurin
1125 mg loading dose, then 500 mg po QD until disease progression, toxicity, or maximum 3 years
Other Names:
Drug: docetaxel
75 mg/m^2 IV, every 21 days, six 21-day cycles, maximum 10 cycles
Drug: prednisone
5 mg po BID, six 21-day cycles
|
| Placebo Comparator: docetaxel + prednisone + placebo Regimen B: docetaxel 75 mg/m^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by po, QD placebo for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
Drug: placebo
Loading dose, then po QD until unblinding
|
| Experimental: docetaxel + prednisone + enzastaurin (modified Regimen A) Modified Regimen A, including pharmacokinetic (PK) characterization: Participants were treated with a modified investigational regimen with no dose escalation: docetaxel 75 mg/m2, IV was administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, enzastaurin was given as a loading dose of 1125 mg starting on Day 4, followed by enzastaurin 500 mg po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance). |
Drug: enzastaurin
1125 mg loading dose, then 500 mg po QD until disease progression, toxicity, or maximum 3 years
Other Names:
Drug: docetaxel
75 mg/m^2 IV, every 21 days, six 21-day cycles, maximum 10 cycles
Drug: prednisone
5 mg po BID, six 21-day cycles
|
Outcome Measures
Primary Outcome Measures
- Part 2: Percentage of Participants With Objective Tumor Response (Response Rate) [Baseline up to 3 years]
Response using Response Evaluation Criteria In Solid Tumors (RECIST). Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Objective response rate (%)=number of objective responders divided by the number of participants qualified for efficacy analysis *100, where objective responders are those participants who have met criteria either for CR or PR.
Secondary Outcome Measures
- Percentage of Participants Exhibiting a Decline in Prostate-Specific Androgen (PSA) From Baseline ≥30% Within First 3 Months of Treatment [Baseline up to 3 months]
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. Decline in PSA of ≥30% from baseline within the first 3 months of treatment was calculated.
- Prostate-Specific Androgen (PSA) Velocity at 2 Months [Baseline up to 2 months]
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity.
- Prostate-Specific Androgen (PSA) Velocity at 3 Months [Baseline up to 3 months]
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity.
- Part 2: Progression Free Survival (PFS) [Baseline to measured PD (up to 487 days)]
PFS was defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). PD is ≥20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died and who did not have PD, PFS was censored at the date of the last progression-free assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. No participant completed a full cycle of therapy and thus no formal analysis was performed.
- Part 2: Overall Survival (OS) [Baseline to death (up to 642 days)]
Overall survival (OS) time is defined as the time from the date of diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date.
- Part 2: Duration of Response [First objective response to PD/death/PSA returning to 50% or more than the original baseline value (up to 616 days)]
Duration of response is defined as the time from date of objective response to progressive disease (PD) or death or prostate-specific androgen (PSA) returning to at least 50% from original baseline value.
- Number of Participants With Adverse Events (AEs) [Baseline through 3 years]
A listing of serious AEs (SAEs) and all other non-serious AEs is included in the Reported Adverse Event Module.
- Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020) [Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose]
Cmax,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
- Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020) [Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose; Part 2: Cycle 2, Day 1 - predose, 1-3, and 4-9 hours postdose]
AUCτ,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
- Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Docetaxel [Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose]
Cmax was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
- Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Docetaxel [Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose]
AUC(0-∞) was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%).
- Tumor Markers [Baseline up to 36 months]
Pharmacogenomic (PGx) work on S032 was cancelled due to the limited number of tissue samples collected and the lack of clinical efficacy (responders) to enzastaurin. Potential biomarkers would have been assessed by dividing participants into low and high expression classes.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
You are at least 18 years old.
-
You live close enough to the doctor's office to attend all of your required visits.
-
You have not been treated with chemotherapy for your prostate cancer.
-
Your organs must be functioning properly.
Exclusion Criteria:
-
You are unable to swallow pills.
-
You have another serious illness besides your prostate cancer.
-
You have taken another experimental drug within the last 30 days.
-
You have a serious heart condition.
-
You are receiving another anti-cancer therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Fullerton | California | United States | 92835 |
| 2 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Los Angeles | California | United States | 90093 |
| 3 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Northridge | California | United States | 91328 |
| 4 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Redondo Beach | California | United States | 90277 |
| 5 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Santa Barbara | California | United States | 93105 |
| 6 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Santa Maria | California | United States | 93454 |
| 7 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Miami | Florida | United States | 33179 |
| 8 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chicago | Illinois | United States | 60637 |
| 9 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Harvey | Illinois | United States | 60426 |
| 10 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Minneapolis | Minnesota | United States | 55404 |
| 11 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Columbia | Missouri | United States | 65201 |
| 12 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kansas City | Missouri | United States | 64128 |
| 13 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Billings | Montana | United States | 59101 |
| 14 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Henderson | Nevada | United States | 89169 |
| 15 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Las Cruces | New Mexico | United States | 88011 |
| 16 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Raleigh | North Carolina | United States | 27607 |
| 17 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Cleveland | Ohio | United States | 44195 |
| 18 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Memphis | Tennessee | United States | 38138 |
| 19 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Dallas | Texas | United States | 75246 |
| 20 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | The Woodlands | Texas | United States | 77380 |
| 21 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Newport News | Virginia | United States | 23606 |
| 22 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Vancouver | Washington | United States | 98684 |
| 23 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Erlangen | Germany | 91054 | |
| 24 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hamburg | Germany | 22399 | |
| 25 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Mannheim | Germany | 68163 | |
| 26 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Como | Italy | 22100 | |
| 27 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Orbassano | Italy | 10043 | |
| 28 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | San Sisto | Italy | 06156 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00466440
Other Study ID Numbers:
- 11311
- H6Q-MC-S032
First Posted:
Apr 27, 2007
Last Update Posted:
Nov 6, 2020
Last Verified:
Oct 1, 2020
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|---|
| Arm/Group Description | Participants were treated with modified Regimen A (modified investigational): docetaxel 75 milligrams per square meter (mg/m^2), intravenous (IV) given on Day 1 every 3 weeks, and prednisone 5 milligrams (mg) oral (po), twice daily (BID) in combination with enzastaurin, starting loading dose on Day 4. | Regimen A: docetaxel 75 mg/m^2, IV given on Day 1 every 3 weeks and prednisone 5 mg po, BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Period Title: Overall Study | |||
| STARTED | 14 | 48 | 46 |
| Received at Least One Dose of Study Drug | 14 | 47 | 41 |
| COMPLETED | 0 | 36 | 34 |
| NOT COMPLETED | 14 | 12 | 12 |
Baseline Characteristics
| Arm/Group Title | Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants were treated with modified Regimen A (modified investigational): docetaxel 75 mg/m2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID in combination with enzastaurin, starting loading dose on Day 4. | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. | Total of all reporting groups |
| Overall Participants | 14 | 48 | 46 | 108 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
66.8
(7.29)
|
69.9
(7.66)
|
70
(8.1)
|
69.54
(7.81)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Male |
14
100%
|
48
100%
|
46
100%
|
108
100%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Black or African American |
0
0%
|
8
16.7%
|
7
15.2%
|
15
13.9%
|
| White |
14
100%
|
39
81.3%
|
33
71.7%
|
86
79.6%
|
| Hispanic |
0
0%
|
0
0%
|
6
13%
|
6
5.6%
|
| East Asian |
0
0%
|
1
2.1%
|
0
0%
|
1
0.9%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
14
100%
|
44
91.7%
|
39
84.8%
|
97
89.8%
|
| Germany |
0
0%
|
3
6.3%
|
4
8.7%
|
7
6.5%
|
| Italy |
0
0%
|
1
2.1%
|
3
6.5%
|
4
3.7%
|
Outcome Measures
| Title | Part 2: Percentage of Participants With Objective Tumor Response (Response Rate) |
|---|---|
| Description | Response using Response Evaluation Criteria In Solid Tumors (RECIST). Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes that do not meet above criteria. Objective response rate (%)=number of objective responders divided by the number of participants qualified for efficacy analysis *100, where objective responders are those participants who have met criteria either for CR or PR. |
| Time Frame | Baseline up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants from Part 2 group, who received at least one dose of study drug. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization. |
| Arm/Group Title | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Arm/Group Description | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 46 | 40 |
| Number (90% Confidence Interval) [percentage of participants] |
15.2
108.6%
|
15.0
31.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2: Docetaxel + Prednisone + Enzastaurin, Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 90% -12.52 to 12.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The objective response rates and the 90% confidence intervals were estimated for the qualified participants using unadjusted normal approximation for binomial proportions (z approximation). | |
| Title | Percentage of Participants Exhibiting a Decline in Prostate-Specific Androgen (PSA) From Baseline ≥30% Within First 3 Months of Treatment |
|---|---|
| Description | PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. Decline in PSA of ≥30% from baseline within the first 3 months of treatment was calculated. |
| Time Frame | Baseline up to 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants having baseline and at least 1 postbaseline PSA response within the first 3 months of treatment. |
| Arm/Group Title | Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|---|
| Arm/Group Description | Participants were treated with modified Regimen A (modified investigational): docetaxel 75 mg/m2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID in combination with enzastaurin, starting loading dose on Day 4. | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 9 | 28 | 29 |
| Number (90% Confidence Interval) [percentage of participants] |
69.2
494.3%
|
60.9
126.9%
|
72.5
157.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2: Docetaxel + Prednisone + Placebo, Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3606 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | -11.6 | |
| Confidence Interval |
(2-Sided) 90% -28.21 to 4.95 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Prostate-Specific Androgen (PSA) Velocity at 2 Months |
|---|---|
| Description | PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity. |
| Time Frame | Baseline up to 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid baseline and at least 1 postbaseline PSA measurement within the first 2 months of treatment. |
| Arm/Group Title | Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|---|
| Arm/Group Description | Participants were treated with modified Regimen A (modified investigational): docetaxel 75 mg/m2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID in combination with enzastaurin, starting loading dose on Day 4. | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 13 | 46 | 40 |
| Mean (90% Confidence Interval) [microgram per liter (ug/L) per month] |
-0.56
|
-0.29
|
-0.55
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2: Docetaxel + Prednisone + Placebo, Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0720 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.26 | |
| Confidence Interval |
(2-Sided) 90% -0.02 to 0.55 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Prostate-Specific Androgen (PSA) Velocity at 3 Months |
|---|---|
| Description | PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity. |
| Time Frame | Baseline up to 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a valid baseline and at least 1 postbaseline PSA measurement within the first 3 months of treatment. |
| Arm/Group Title | Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|---|
| Arm/Group Description | Participants were treated with modified Regimen A (modified investigational): docetaxel 75 mg/m2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID in combination with enzastaurin, starting loading dose on Day 4. | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 13 | 46 | 40 |
| Mean (90% Confidence Interval) [ug/L per month] |
-0.45
|
-0.30
|
-0.45
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2: Docetaxel + Prednisone + Placebo, Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1697 |
| Comments | ||
| Method | t-test, 1 sided | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
| Estimated Value | 0.15 | |
| Confidence Interval |
(2-Sided) 90% -0.07 to 0.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part 2: Progression Free Survival (PFS) |
|---|---|
| Description | PFS was defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). PD is ≥20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. For participants not known to have died and who did not have PD, PFS was censored at the date of the last progression-free assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. No participant completed a full cycle of therapy and thus no formal analysis was performed. |
| Time Frame | Baseline to measured PD (up to 487 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants from Part 2 group, who received at least one dose of study drug. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization. |
| Arm/Group Title | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Arm/Group Description | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 46 | 40 |
| Median (90% Confidence Interval) [Days] |
229
|
213
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2: Docetaxel + Prednisone + Enzastaurin, Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5240 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.86 | |
| Confidence Interval |
(2-Sided) 95% 0.5 to 1.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part 2: Overall Survival (OS) |
|---|---|
| Description | Overall survival (OS) time is defined as the time from the date of diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date. |
| Time Frame | Baseline to death (up to 642 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants from Part 2 group, who received at least one dose of study drug. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization. |
| Arm/Group Title | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Arm/Group Description | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 48 | 46 |
| Median (90% Confidence Interval) [days] |
462
|
448
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2: Docetaxel + Prednisone + Enzastaurin, Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4407 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.74 | |
| Confidence Interval |
(2-Sided) 95% 0.3 to 1.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Part 2: Duration of Response |
|---|---|
| Description | Duration of response is defined as the time from date of objective response to progressive disease (PD) or death or prostate-specific androgen (PSA) returning to at least 50% from original baseline value. |
| Time Frame | First objective response to PD/death/PSA returning to 50% or more than the original baseline value (up to 616 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants from Part 2 group, who received at least one dose of study drug. Per protocol, Part 1 was not included as it is an open-label safety lead-in portion with PK characterization. |
| Arm/Group Title | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Arm/Group Description | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 46 | 40 |
| Median (90% Confidence Interval) [days] |
231
|
201
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Part 2: Docetaxel + Prednisone + Enzastaurin, Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3449 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.75 | |
| Confidence Interval |
(2-Sided) 95% 0.4 to 1.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Adverse Events (AEs) |
|---|---|
| Description | A listing of serious AEs (SAEs) and all other non-serious AEs is included in the Reported Adverse Event Module. |
| Time Frame | Baseline through 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population was defined as all enrolled participants who received at least one dose of study drug. |
| Arm/Group Title | Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|---|
| Arm/Group Description | Participants were treated with modified Regimen A (modified investigational): docetaxel 75 mg/m2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID in combination with enzastaurin, starting loading dose on Day 4. | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 14 | 47 | 41 |
| SAEs |
8
57.1%
|
16
33.3%
|
14
30.4%
|
| Other Non-Serious AEs |
14
100%
|
47
97.9%
|
41
89.1%
|
| Title | Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020) |
|---|---|
| Description | Cmax,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%). |
| Time Frame | Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| For Part 1, pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected. |
| Arm/Group Title | Enzastaurin 500 mg QD Alone | Enzastaurin 500 mg QD + Docetaxel 75 mg/m^2 + Prednisone |
|---|---|---|
| Arm/Group Description | Enzastaurin, LSN326020 and total analyte (enzastaurin + LSN326020) on Cycle 1 Day 21 (enzastaurin alone) following enzastaurin 500 mg oral (po) daily (QD). | Enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020) on Cycle 2 Day 1 (enzastaurin + docetaxel + prednisone) following enzastaurin 500 mg po QD. |
| Measure Participants | 9 | 7 |
| Enzastaurin |
870
(84)
|
778
(39)
|
| LSN326020 |
664
(45)
|
667
(30)
|
| Total Analyte |
1540
(62)
|
1450
(32)
|
| Title | Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020) |
|---|---|
| Description | AUCτ,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%). |
| Time Frame | Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose; Part 2: Cycle 2, Day 1 - predose, 1-3, and 4-9 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected. |
| Arm/Group Title | Enzastaurin 500 mg QD Alone | Enzastaurin 500 mg QD+Docetaxel 75 mg/m^2+Prednisone (Part 1) | Enzastaurin 500 mg QD+Docetaxel 75 mg/m^2+Prednisone (Part 2) |
|---|---|---|---|
| Arm/Group Description | Enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020) on Cycle 1 Day 21 (enzastaurin alone) following enzastaurin 500 mg oral (po) daily (QD). | Enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020) on Cycle 2 Day 1 (enzastaurin + docetaxel + prednisone) following enzastaurin 500 mg po QD. | Enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020) on Cycle 2 Day 1 (enzastaurin + docetaxel + prednisone) following enzastaurin 500 mg po QD. |
| Measure Participants | 7 | 6 | 9 |
| Enzastaurin |
12900
(79)
|
13100
(26)
|
20800
(104)
|
| LSN326020 |
15200
(35)
|
15700
(20)
|
24800
(52)
|
| Total Analyte |
28700
(49)
|
29000
(18)
|
47800
(74)
|
| Title | Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Docetaxel |
|---|---|
| Description | Cmax was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%). |
| Time Frame | Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| For Part 1, pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected. |
| Arm/Group Title | Docetaxel 75 mg/m^2 Alone | Enzastaurin 500 mg QD + Docetaxel 75 mg/m^2 + Prednisone |
|---|---|---|
| Arm/Group Description | Docetaxel (75 mg/m^2) following 1.0 hour intravenous infusion on Cycle 1 Day 1 (Docetaxel + Prednisone). | Docetaxel (75 mg/m^2) following 1.0 hour intravenous infusion on Cycle 2 Day 1 (Docetaxel + Prednisone + Enzastaurin). |
| Measure Participants | 13 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [nanograms per millimeter (ng/mL)] |
2230
(21)
|
1840
(22)
|
| Title | Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Docetaxel |
|---|---|
| Description | AUC(0-∞) was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%). |
| Time Frame | Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose |
Outcome Measure Data
| Analysis Population Description |
|---|
| For Part 1, pharmacokinetic analyses were conducted for individual participants who received at least one dose of study drug and had pharmacokinetic samples collected. |
| Arm/Group Title | Docetaxel 75 mg/m^2 Alone | Enzastaurin 500 mg QD + Docetaxel 75 mg/m^2 + Prednisone |
|---|---|---|
| Arm/Group Description | Docetaxel (75 mg/m^2) following 1.0 hour intravenous infusion on Cycle 1 Day 1 (Docetaxel + Prednisone). | Docetaxel (75 mg/m^2) following 1.0 hour intravenous infusion on Cycle 2 Day 1 (Docetaxel + Prednisone + Enzastaurin). |
| Measure Participants | 13 | 10 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
2350
(26)
|
1750
(20)
|
| Title | Tumor Markers |
|---|---|
| Description | Pharmacogenomic (PGx) work on S032 was cancelled due to the limited number of tissue samples collected and the lack of clinical efficacy (responders) to enzastaurin. Potential biomarkers would have been assessed by dividing participants into low and high expression classes. |
| Time Frame | Baseline up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Data were not collected for any participant due to low samples. |
| Arm/Group Title | Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo |
|---|---|---|---|
| Arm/Group Description | Participants were treated with modified Regimen A (modified investigational): docetaxel 75 mg/m2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID in combination with enzastaurin, starting loading dose on Day 4. | Regimen A: docetaxel 75 mg/m^2 IV given on Day 1 every 3 weeks and prednisone 5 mg po BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2 IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. |
| Measure Participants | 0 | 0 | 0 |
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo | |||
| Arm/Group Description | Participants were treated with modified Regimen A (modified investigational): docetaxel 75 milligrams per square meter (mg/m^2), intravenous (IV) given on Day 1 every 3 weeks, and prednisone 5 milligrams (mg) oral (po), twice daily (BID) in combination with enzastaurin, starting loading dose on Day 4. | Regimen A: docetaxel 75 mg/m^2, IV given on Day 1 every 3 weeks and prednisone 5 mg po, BID with enzastaurin, starting loading dose 1 day prior to chemotherapy. | Regimen B: docetaxel 75 mg/m^2, IV is administered on Day 1 every 3 weeks for 6 cycles (maximum up to 10 cycles) and prednisone 5 mg po, BID every day. In Cycle 1, placebo is given as a loading dose on the day prior to docetaxel and prednisone therapy, followed by placebo po, QD for the remaining Period 2 (chemotherapy) and Period 3 (maintenance), until unblinding. | |||
All Cause Mortality |
||||||
| Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/14 (57.1%) | 16/47 (34%) | 14/41 (34.1%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Febrile neutropenia | 2/14 (14.3%) | 3 | 6/47 (12.8%) | 7 | 2/41 (4.9%) | 2 |
| Leukopenia | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Neutropenia | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Thrombocytopenia | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Cardiac disorders | ||||||
| Acute myocardial infarction | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Atrial fibrillation | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Myocardial infarction | 0/14 (0%) | 0 | 2/47 (4.3%) | 2 | 0/41 (0%) | 0 |
| Sinus bradycardia | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Anal fistula | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Colitis | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Constipation | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 2/41 (4.9%) | 2 |
| Diarrhoea | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 1/41 (2.4%) | 1 |
| Dysphagia | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Faecaloma | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Ileus | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Intestinal perforation | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Nausea | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 2/41 (4.9%) | 2 |
| Vomiting | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| General disorders | ||||||
| Asthenia | 0/14 (0%) | 0 | 2/47 (4.3%) | 2 | 1/41 (2.4%) | 1 |
| Chest pain | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Extravasation | 2/14 (14.3%) | 2 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Pain | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Pyrexia | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Immune system disorders | ||||||
| Hypersensitivity | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Infections and infestations | ||||||
| Fungaemia | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Infection | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Pelvic abscess | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Pneumonia | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 2/41 (4.9%) | 2 |
| Sepsis | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 0/41 (0%) | 0 |
| Septic shock | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Urinary tract infection | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Wound | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Investigations | ||||||
| Haemoglobin decreased | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Cachexia | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Dehydration | 0/14 (0%) | 0 | 2/47 (4.3%) | 2 | 1/41 (2.4%) | 1 |
| Fluid overload | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Hyperglycaemia | 0/14 (0%) | 0 | 2/47 (4.3%) | 2 | 0/41 (0%) | 0 |
| Hypokalaemia | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Hyponatraemia | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Muscular weakness | 0/14 (0%) | 0 | 1/47 (2.1%) | 2 | 0/41 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Metastases to bone | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Oesophageal carcinoma | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Nervous system disorders | ||||||
| Dizziness | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Hydrocephalus | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Myasthenia gravis | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Syncope | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Psychiatric disorders | ||||||
| Confusional state | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Renal and urinary disorders | ||||||
| Cystitis haemorrhagic | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Haematuria | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Hydronephrosis | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Renal failure | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Renal failure acute | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Ureteric obstruction | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Urinary retention | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Urinary tract obstruction | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory distress syndrome | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Acute respiratory failure | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Atelectasis | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Dyspnoea | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 2/41 (4.9%) | 2 |
| Pneumonia aspiration | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Pneumonitis | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Pulmonary embolism | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Pulmonary fibrosis | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Decubitus ulcer | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/14 (0%) | 0 | 2/47 (4.3%) | 2 | 1/41 (2.4%) | 1 |
| Thrombosis | 2/14 (14.3%) | 2 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Part 1: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Enzastaurin | Part 2: Docetaxel + Prednisone + Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/14 (100%) | 47/47 (100%) | 41/41 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/14 (7.1%) | 1 | 14/47 (29.8%) | 17 | 7/41 (17.1%) | 7 |
| Leukopenia | 2/14 (14.3%) | 3 | 9/47 (19.1%) | 35 | 5/41 (12.2%) | 10 |
| Lymphopenia | 9/14 (64.3%) | 11 | 5/47 (10.6%) | 7 | 11/41 (26.8%) | 14 |
| Neutropenia | 0/14 (0%) | 0 | 18/47 (38.3%) | 55 | 14/41 (34.1%) | 19 |
| Thrombocytopenia | 1/14 (7.1%) | 2 | 4/47 (8.5%) | 4 | 2/41 (4.9%) | 4 |
| Cardiac disorders | ||||||
| Cardio-Respiratory arrest | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Supraventricular tachycardia | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Eye disorders | ||||||
| Diplopia | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Dry eye | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Lacrimation increased | 2/14 (14.3%) | 2 | 3/47 (6.4%) | 3 | 1/41 (2.4%) | 1 |
| Strabismus | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Vision blurred | 3/14 (21.4%) | 3 | 1/47 (2.1%) | 1 | 4/41 (9.8%) | 4 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Abdominal distension | 2/14 (14.3%) | 2 | 1/47 (2.1%) | 2 | 1/41 (2.4%) | 1 |
| Abdominal pain | 2/14 (14.3%) | 5 | 8/47 (17%) | 10 | 3/41 (7.3%) | 3 |
| Abdominal pain upper | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 0/41 (0%) | 0 |
| Ascites | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Constipation | 5/14 (35.7%) | 6 | 11/47 (23.4%) | 16 | 6/41 (14.6%) | 7 |
| Diarrhoea | 7/14 (50%) | 7 | 22/47 (46.8%) | 35 | 15/41 (36.6%) | 20 |
| Dry mouth | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Dyspepsia | 3/14 (21.4%) | 3 | 4/47 (8.5%) | 5 | 4/41 (9.8%) | 5 |
| Faecal incontinence | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 0/41 (0%) | 0 |
| Haemorrhoids | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Lip dry | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Nausea | 7/14 (50%) | 8 | 21/47 (44.7%) | 33 | 11/41 (26.8%) | 14 |
| Oral disorder | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Rectal haemorrhage | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Sensitivity of teeth | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Stomatitis | 0/14 (0%) | 0 | 5/47 (10.6%) | 5 | 2/41 (4.9%) | 3 |
| Vomiting | 1/14 (7.1%) | 1 | 14/47 (29.8%) | 16 | 4/41 (9.8%) | 4 |
| General disorders | ||||||
| Asthenia | 0/14 (0%) | 0 | 10/47 (21.3%) | 13 | 3/41 (7.3%) | 3 |
| Extravasation | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Fatigue | 7/14 (50%) | 9 | 26/47 (55.3%) | 34 | 25/41 (61%) | 32 |
| Feeling cold | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 2/41 (4.9%) | 2 |
| Gait disturbance | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 3/41 (7.3%) | 3 |
| Malaise | 0/14 (0%) | 0 | 5/47 (10.6%) | 6 | 2/41 (4.9%) | 2 |
| Mucosal inflammation | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 2/41 (4.9%) | 2 |
| Oedema | 2/14 (14.3%) | 2 | 1/47 (2.1%) | 1 | 2/41 (4.9%) | 2 |
| Oedema peripheral | 0/14 (0%) | 0 | 8/47 (17%) | 10 | 9/41 (22%) | 10 |
| Pain | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 1/41 (2.4%) | 2 |
| Infections and infestations | ||||||
| Cellulitis | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 2 | 0/41 (0%) | 0 |
| Intervertebral discitis | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Opportunistic infection | 2/14 (14.3%) | 2 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Oral herpes | 2/14 (14.3%) | 2 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Rhinitis | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 1/41 (2.4%) | 1 |
| Upper respiratory tract infection | 0/14 (0%) | 0 | 4/47 (8.5%) | 4 | 2/41 (4.9%) | 2 |
| Urinary tract infection | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 0/41 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Contusion | 0/14 (0%) | 0 | 6/47 (12.8%) | 7 | 2/41 (4.9%) | 2 |
| Injury | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 0/14 (0%) | 0 | 7/47 (14.9%) | 10 | 1/41 (2.4%) | 1 |
| Aspartate aminotransferase increased | 2/14 (14.3%) | 3 | 9/47 (19.1%) | 13 | 7/41 (17.1%) | 8 |
| Blood albumin decreased | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 0/41 (0%) | 0 |
| Blood alkaline phosphatase increased | 2/14 (14.3%) | 2 | 3/47 (6.4%) | 3 | 0/41 (0%) | 0 |
| Blood calcium decreased | 3/14 (21.4%) | 3 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Blood creatinine increased | 6/14 (42.9%) | 7 | 6/47 (12.8%) | 7 | 2/41 (4.9%) | 2 |
| Blood glucose increased | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Blood phosphorus decreased | 2/14 (14.3%) | 2 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Blood potassium decreased | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Blood potassium increased | 3/14 (21.4%) | 4 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Blood sodium decreased | 1/14 (7.1%) | 2 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Blood uric acid decreased | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Blood uric acid increased | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 2 | 1/41 (2.4%) | 1 |
| Haemoglobin decreased | 5/14 (35.7%) | 5 | 5/47 (10.6%) | 5 | 9/41 (22%) | 11 |
| Neutrophil count decreased | 3/14 (21.4%) | 3 | 2/47 (4.3%) | 6 | 4/41 (9.8%) | 4 |
| Platelet count decreased | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 2 | 1/41 (2.4%) | 1 |
| Weight decreased | 2/14 (14.3%) | 2 | 4/47 (8.5%) | 4 | 7/41 (17.1%) | 7 |
| Weight increased | 0/14 (0%) | 0 | 1/47 (2.1%) | 1 | 3/41 (7.3%) | 3 |
| White blood cell count decreased | 3/14 (21.4%) | 4 | 4/47 (8.5%) | 8 | 2/41 (4.9%) | 3 |
| Metabolism and nutrition disorders | ||||||
| Anorexia | 4/14 (28.6%) | 4 | 12/47 (25.5%) | 16 | 15/41 (36.6%) | 16 |
| Decreased appetite | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Dehydration | 0/14 (0%) | 0 | 7/47 (14.9%) | 9 | 3/41 (7.3%) | 4 |
| Hyperglycaemia | 1/14 (7.1%) | 1 | 14/47 (29.8%) | 17 | 8/41 (19.5%) | 13 |
| Hyperkalaemia | 2/14 (14.3%) | 2 | 4/47 (8.5%) | 6 | 1/41 (2.4%) | 1 |
| Hypocalcaemia | 2/14 (14.3%) | 2 | 2/47 (4.3%) | 2 | 2/41 (4.9%) | 2 |
| Hypokalaemia | 1/14 (7.1%) | 1 | 6/47 (12.8%) | 8 | 4/41 (9.8%) | 5 |
| Hyponatraemia | 0/14 (0%) | 0 | 3/47 (6.4%) | 4 | 3/41 (7.3%) | 4 |
| Hypophosphataemia | 0/14 (0%) | 0 | 2/47 (4.3%) | 2 | 4/41 (9.8%) | 4 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 4/14 (28.6%) | 5 | 6/47 (12.8%) | 7 | 8/41 (19.5%) | 8 |
| Back pain | 2/14 (14.3%) | 2 | 8/47 (17%) | 9 | 8/41 (19.5%) | 8 |
| Bone pain | 0/14 (0%) | 0 | 2/47 (4.3%) | 2 | 3/41 (7.3%) | 3 |
| Joint stiffness | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Muscle spasms | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 1 | 2/41 (4.9%) | 2 |
| Muscular weakness | 2/14 (14.3%) | 2 | 6/47 (12.8%) | 7 | 1/41 (2.4%) | 1 |
| Musculoskeletal pain | 2/14 (14.3%) | 2 | 5/47 (10.6%) | 5 | 2/41 (4.9%) | 2 |
| Myalgia | 0/14 (0%) | 0 | 3/47 (6.4%) | 5 | 3/41 (7.3%) | 4 |
| Osteoarthritis | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Pain in extremity | 3/14 (21.4%) | 3 | 6/47 (12.8%) | 8 | 7/41 (17.1%) | 7 |
| Trigger finger | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Seborrhoeic keratosis | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Nervous system disorders | ||||||
| Dizziness | 2/14 (14.3%) | 2 | 11/47 (23.4%) | 16 | 9/41 (22%) | 11 |
| Dysgeusia | 3/14 (21.4%) | 3 | 14/47 (29.8%) | 18 | 8/41 (19.5%) | 8 |
| Headache | 3/14 (21.4%) | 3 | 3/47 (6.4%) | 3 | 1/41 (2.4%) | 1 |
| Neuropathy peripheral | 4/14 (28.6%) | 4 | 6/47 (12.8%) | 8 | 8/41 (19.5%) | 11 |
| Peripheral sensory neuropathy | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 3/41 (7.3%) | 3 |
| Sciatica | 2/14 (14.3%) | 2 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Spinal cord compression | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 1/41 (2.4%) | 1 |
| Depression | 1/14 (7.1%) | 1 | 3/47 (6.4%) | 3 | 1/41 (2.4%) | 1 |
| Insomnia | 2/14 (14.3%) | 2 | 3/47 (6.4%) | 3 | 3/41 (7.3%) | 3 |
| Renal and urinary disorders | ||||||
| Haematuria | 1/14 (7.1%) | 2 | 4/47 (8.5%) | 4 | 2/41 (4.9%) | 2 |
| Nocturia | 2/14 (14.3%) | 2 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Pollakiuria | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 4/41 (9.8%) | 5 |
| Urinary bladder haemorrhage | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Urinary retention | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 3/41 (7.3%) | 3 |
| Reproductive system and breast disorders | ||||||
| Pelvic pain | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 1 | 1/41 (2.4%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 3/14 (21.4%) | 3 | 4/47 (8.5%) | 6 | 10/41 (24.4%) | 11 |
| Dysphonia | 2/14 (14.3%) | 2 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Dyspnoea | 5/14 (35.7%) | 6 | 9/47 (19.1%) | 10 | 6/41 (14.6%) | 7 |
| Dyspnoea exertional | 3/14 (21.4%) | 3 | 1/47 (2.1%) | 1 | 0/41 (0%) | 0 |
| Epistaxis | 0/14 (0%) | 0 | 3/47 (6.4%) | 4 | 0/41 (0%) | 0 |
| Nasal congestion | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 1/41 (2.4%) | 1 |
| Pharyngolaryngeal pain | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 4/41 (9.8%) | 4 |
| Pleural effusion | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Rhinorrhoea | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 1/41 (2.4%) | 1 |
| Sinus congestion | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 0/41 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Alopecia | 12/14 (85.7%) | 12 | 21/47 (44.7%) | 21 | 22/41 (53.7%) | 23 |
| Dry skin | 2/14 (14.3%) | 2 | 2/47 (4.3%) | 2 | 2/41 (4.9%) | 2 |
| Erythema | 0/14 (0%) | 0 | 4/47 (8.5%) | 4 | 1/41 (2.4%) | 1 |
| Nail discolouration | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 1/41 (2.4%) | 1 |
| Nail disorder | 5/14 (35.7%) | 5 | 11/47 (23.4%) | 11 | 10/41 (24.4%) | 10 |
| Palmar-Plantar erythrodysaesthesia syndrome | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Rash | 0/14 (0%) | 0 | 5/47 (10.6%) | 5 | 5/41 (12.2%) | 5 |
| Skin discolouration | 0/14 (0%) | 0 | 3/47 (6.4%) | 3 | 0/41 (0%) | 0 |
| Swelling face | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Surgery | 1/14 (7.1%) | 1 | 0/47 (0%) | 0 | 0/41 (0%) | 0 |
| Vascular disorders | ||||||
| Flushing | 1/14 (7.1%) | 1 | 1/47 (2.1%) | 1 | 2/41 (4.9%) | 2 |
| Hypotension | 1/14 (7.1%) | 1 | 6/47 (12.8%) | 8 | 3/41 (7.3%) | 3 |
| Phlebitis | 0/14 (0%) | 0 | 0/47 (0%) | 0 | 3/41 (7.3%) | 4 |
| Thrombosis | 1/14 (7.1%) | 1 | 2/47 (4.3%) | 2 | 0/41 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5979 |
| ClinicalTrials.gov@lilly.com |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00466440
Other Study ID Numbers:
- 11311
- H6Q-MC-S032
First Posted:
Apr 27, 2007
Last Update Posted:
Nov 6, 2020
Last Verified:
Oct 1, 2020