A Study in Participants With Acute Leukemia
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01214603
Collaborator
(none)
20
4
1
25
5
0.2
Study Details
Study Description
Brief Summary
This study is a multicenter, non-randomized, open-label, Phase 2 study of intravenous LY2090314 in participants with acute leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of LY2090314 in Participants With Acute Leukemia
Study Start Date
:
Nov 1, 2010
Actual Primary Completion Date
:
Dec 1, 2012
Actual Study Completion Date
:
Dec 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY2090314 Cohort 1: 40 milligrams (mg) LY2090314 administered on Days 1, 8, and 15 of a 28-day cycle for at least two (2) 28-day cycles. Participants experiencing clinical benefit may continue treatment until after the discontinuation criteria are met. Due to a protocol amendment on September 2010, the study added 2 additional treatment schedules/cohorts. Cohort 2: 40 mg dose given on Days 1, 5, and 9 of a 21-day cycle. Cohort 3: 40 mg dose given on Days 1, 5, 9, and 12 of a 21-day cycle. Participants experiencing clinical benefit may continue treatment until after the discontinuation criteria are met. |
Drug: LY2090314
Administered intravenously
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) [Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]]
Drug-related events were defined as treatment-emergent serious and other non-serious AEs that were considered by the investigator to be related to study drug. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Secondary Outcome Measures
- Number of Participants With Best Response of Complete Response or Partial Response [Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)]
The Revised International Working Group criteria were used to determine the response for participants with acute myelogenous leukemia (AML). Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as <5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100*10^9/Liter (L) and absolute neutrophil count (ANC) ≥1*10^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate.
- Percentage of Participants With Best Response of Complete Response or Partial Response [Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles)]
The Revised International Working Group criteria were used to determine the response for participants with AML. Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as <5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100*10^9/L and ANC ≥1*10^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Percentage of participants=[(number of participants with CR or PR)/(number of participants treated)]*100.
- Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)] [Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)]]
AUC(0-8) was estimated from the plasma drug concentration time profile.
- PK: AUC From Time 0 to Infinity [AUC(0-inf)] [Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)]]
AUC(0-inf) was estimated from the plasma drug concentration time profile.
- PK: Maximum Concentration (Cmax) [Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)]]
Cmax is the maximum observed concentration estimated from the plasma drug concentration time profile.
- Percent Change From Predose Beta (β)-Catenin Levels [Cycle 1: D1 and D9 (predose, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion started); Cycle 1: D5, D8, and D12 and C2 through C9: D1 (predose, 2 h after infusion started); Cycle 1: D15 (predose, 1 h, 2 h, 4 h, and 8 h after infusion started)]
Percent change=[(β-catenin level postdose-predose level)/(predose β-catenin levels)]*100. Participants in Cohort 1 had β-catenin samples collected on Cycle 1: D1, D8, and D15, and Cycles 2 through 9: D1. Participants in Cohort 2 had β-catenin samples collected on Cycle 1: D1, D5, and D9 and Cycles 2 through 9: D1. Participants in Cohort 3 had β-catenin samples collected on Cycle 1: D1, D5, D9, and D12 and Cycles 2 through 9: D1.
- Number of Participants Who Died [Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)]]
The number of participants who died while on study treatment and the number of participants who died during the 30-day follow-up (30 days post last dose) are reported.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Participants must have confirmed diagnosis of one of the following:
-
Acute myelogenous leukemia (AML) that is refractory or relapsed disease. If participants have acute promyelocytic leukemia (APL), they must have received prior all-trans retinoic acid and arsenic trioxide unless ineligible or intolerant to them
-
Untreated AML (de novo or arising from a myelodysplastic syndrome). In the opinion of the investigator, the participant should not be a candidate for standard therapy and a clinical trial is a preferred treatment option
-
Have given written informed consent prior to any study-specific procedures
-
Have adequate organ function including:
-
Hepatic: Bilirubin less than or equal to 1.5 times the upper limit of normal (ULN). Alkaline phosphatase (ALP) and transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] less than or equal to 5 times ULN
-
Renal: Serum creatinine less than or equal to the ULN. No known active renal disease. In rare cases, participants may enter treatment with a serum creatinine greater than the ULN as elevations of serum creatinine may be secondary to dehydration
-
Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
-
Have discontinued all previous approved therapies for acute leukemia, including chemotherapy for at least 14 days, and recovered from the acute effects of therapy. Hydroxyurea used to control peripheral blast count is permitted within the first 2 cycles of treatment on study, but it must be stopped at least 24 hours before study drug administration in Cycle 3
-
Are reliable and willing to be available for the duration of the study and are willing to follow study procedures
-
Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug
-
Females with childbearing potential must have had a negative urine or serum pregnancy test less than or equal to 7 days prior to the first dose of study drug
-
Have an estimated life expectancy of greater than or equal to 6 weeks
Exclusion Criteria:
-
Have received treatment within 14 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication
-
Participants with chronic myelogenous leukemia (CML) including blast crisis phase
-
Participants with known central nervous system (CNS) leukemia by spinal fluid cytology or imaging
-
Have serious pre-existing medical conditions (left to the discretion of the investigator)
-
Have one of the following abnormalities: QTc (Fridericia corrected) interval >450 milliseconds (msec) on screening electrocardiogram (ECG), previous history of QTc prolongation with another medication that required discontinuation, congenital long QT syndrome, previous history of ventricular tachycardia or unexplained syncope, left bundle branch block, or chronic atrial fibrillation
-
Have family history of long QT syndrome or sudden death due to ventricular arrhythmia
-
Concomitant medication that may cause QTc prolongation or induce Torsades de Pointes at the time of study entry
-
Have systolic blood pressure greater than or equal to 160 millimeter of mercury (mm Hg) and diastolic blood pressure greater than or equal to 100 mm Hg
-
Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class II or higher or participants with a history of arrhythmia that is symptomatic or requires treatment
-
Have uncorrected electrolyte disorders including potassium
-
Have other active malignancy (with the exception of basal and squamous cell skin cancer) at time of study entry
-
Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug
-
Have uncontrolled systemic infection
-
Females who are pregnant or lactating
-
Presence of clinical evidence of viral disease caused by human immunodeficiency virus, hepatitis B, or hepatitis C
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. | Chicago | Illinois | United States | 60637 |
| 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. | Minneapolis | Minnesota | United States | 55455 |
| 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. | Durham | North Carolina | United States | 27710 |
| 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. | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01214603
Other Study ID Numbers:
- 13370
- I2H-MC-JWYB
First Posted:
Oct 5, 2010
Last Update Posted:
Nov 19, 2018
Last Verified:
Oct 1, 2018
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Study had safety lead-in phase [40 milligrams (mg) LY2090314 administered using 3 treatment schedules]. Each cohort of participants had different schedule. Safety lead-in data determined if expansion phase opened to enrollment. No participant enrolled in expansion phase. Participants who completed 2 cycles of treatment considered study completers. |
| Arm/Group Title | Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 |
|---|---|---|---|
| Arm/Group Description | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on Day (D)1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Period Title: Overall Study | |||
| STARTED | 7 | 6 | 7 |
| Received at Least 1 Dose of LY2090314 | 7 | 6 | 7 |
| COMPLETED | 2 | 5 | 3 |
| NOT COMPLETED | 5 | 1 | 4 |
Baseline Characteristics
| Arm/Group Title | Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | Total |
|---|---|---|---|---|
| Arm/Group Description | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | Total of all reporting groups |
| Overall Participants | 7 | 6 | 7 | 20 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
75.3
(7.16)
|
61.7
(14.98)
|
67.6
(9.81)
|
68.5
(11.73)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
2
28.6%
|
3
50%
|
5
71.4%
|
10
50%
|
| Male |
5
71.4%
|
3
50%
|
2
28.6%
|
10
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
7
100%
|
6
100%
|
7
100%
|
20
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
2
28.6%
|
2
10%
|
| White |
7
100%
|
6
100%
|
5
71.4%
|
18
90%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||
| United States |
7
100%
|
6
100%
|
7
100%
|
20
100%
|
Outcome Measures
| Title | Number of Participants With 1 or More Study Drug-Related Adverse Events (AEs) or Any Serious AEs (SAEs) |
|---|---|
| Description | Drug-related events were defined as treatment-emergent serious and other non-serious AEs that were considered by the investigator to be related to study drug. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. |
| Time Frame | Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 |
|---|---|---|---|
| Arm/Group Description | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Measure Participants | 7 | 6 | 7 |
| Study Drug-Related AE(s) |
6
85.7%
|
5
83.3%
|
6
85.7%
|
| Study Drug-Related SAE(s) |
0
0%
|
2
33.3%
|
1
14.3%
|
| Title | Number of Participants With Best Response of Complete Response or Partial Response |
|---|---|
| Description | The Revised International Working Group criteria were used to determine the response for participants with acute myelogenous leukemia (AML). Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as <5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100*10^9/Liter (L) and absolute neutrophil count (ANC) ≥1*10^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. |
| Time Frame | Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 |
|---|---|---|---|
| Arm/Group Description | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Measure Participants | 7 | 6 | 7 |
| CR |
0
0%
|
0
0%
|
0
0%
|
| PR |
0
0%
|
0
0%
|
0
0%
|
| Title | Percentage of Participants With Best Response of Complete Response or Partial Response |
|---|---|
| Description | The Revised International Working Group criteria were used to determine the response for participants with AML. Complete response, also known as complete remission (CR) included the following categories: Morphologic CR defined as <5% blasts in an aspirate sample with marrow spicules and with a count of at least 200 nucleated cells, along with peripheral blood levels including platelets ≥100*10^9/L and ANC ≥1*10^9/L, Morphologic CR with incomplete blood count recovery (CRi), Cytogenetic CR, and Molecular CR. Partial response, also known as partial remission (PR) was defined as a decrease of at least 50% in blast count on the bone marrow aspirate. PR required all of the hematologic values for a CR but with a decrease of at least 50% in the percentage of blasts to 5% to 25% in the bone marrow aspirate. Percentage of participants=[(number of participants with CR or PR)/(number of participants treated)]*100. |
| Time Frame | Baseline to progressive disease (up to Cycle 9, 21-day or 28 day cycles) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 |
|---|---|---|---|
| Arm/Group Description | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Measure Participants | 7 | 6 | 7 |
| CR |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| PR |
0.0
0%
|
0.0
0%
|
0.0
0%
|
| Title | Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to 8 Hours (h) Postdose [AUC(0-8)] |
|---|---|
| Description | AUC(0-8) was estimated from the plasma drug concentration time profile. |
| Time Frame | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis. |
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | All participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled. Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Measure Participants | 13 |
| Measure Profiles | 14 |
| Geometric Mean (Geometric Coefficient of Variation) [nanograms*hours per milliliter (ng*h/mL)] |
898
(47)
|
| Title | PK: AUC From Time 0 to Infinity [AUC(0-inf)] |
|---|---|
| Description | AUC(0-inf) was estimated from the plasma drug concentration time profile. |
| Time Frame | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis. |
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | All participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled. Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Measure Participants | 3 |
| Measure Profiles | 3 |
| Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL] |
963
(46.4)
|
| Title | PK: Maximum Concentration (Cmax) |
|---|---|
| Description | Cmax is the maximum observed concentration estimated from the plasma drug concentration time profile. |
| Time Frame | Cycle 1: D1 and/or D9 and/or D15 [predose, 30 minutes (during infusion), up to 24 h after infusion started (1 h, 2 h, 4 h, 6 h, 8 h, and 24 h)] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of study drug and had sufficient postdose samples collected to allow estimation of the PK parameters using noncompartmental methods of analysis. |
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | All participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled. Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Measure Participants | 20 |
| Measure Profiles | 36 |
| Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)] |
476
(56.5)
|
| Title | Percent Change From Predose Beta (β)-Catenin Levels |
|---|---|
| Description | Percent change=[(β-catenin level postdose-predose level)/(predose β-catenin levels)]*100. Participants in Cohort 1 had β-catenin samples collected on Cycle 1: D1, D8, and D15, and Cycles 2 through 9: D1. Participants in Cohort 2 had β-catenin samples collected on Cycle 1: D1, D5, and D9 and Cycles 2 through 9: D1. Participants in Cohort 3 had β-catenin samples collected on Cycle 1: D1, D5, D9, and D12 and Cycles 2 through 9: D1. |
| Time Frame | Cycle 1: D1 and D9 (predose, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion started); Cycle 1: D5, D8, and D12 and C2 through C9: D1 (predose, 2 h after infusion started); Cycle 1: D15 (predose, 1 h, 2 h, 4 h, and 8 h after infusion started) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of study drug and had a predose and at least 1 postdose β-catenin sample collected. |
| Arm/Group Title | Entire Study Population |
|---|---|
| Arm/Group Description | All participants who received at least 1 dose of LY2090314 regardless of the cohort to which they were enrolled. Cohort 1: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. Cohort 2: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. Cohort 3: LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Measure Participants | 18 |
| Cycle 1, Day 1, 1 h postdose |
557.4
(397.49)
|
| Cycle 1, Day 1, 2 h postdose |
513.7
(284.19)
|
| Cycle 1, Day 1, 4 h postdose |
547.6
(342.89)
|
| Cycle 1, Day 1, 8 h postdose |
285.7
(421.91)
|
| Cycle 1, Day 1, 24 h postdose |
83.6
(141.96)
|
| Cycle 1, Day 5, 2 h postdose |
817.2
(576.25)
|
| Cycle 1, Day 8, 2 h postdose |
343.2
(216.26)
|
| Cycle 1, Day 9, 1 h postdose |
736.1
(831.56)
|
| Cycle 1, Day 9, 2 h postdose |
746.5
(728.22)
|
| Cycle 1, Day 9, 4 h postdose |
684.3
(630.99)
|
| Cycle 1, Day 9, 8 h postdose |
141.2
(133.13)
|
| Cycle 1, Day 9, 24 h postdose |
9.1
(99.14)
|
| Cycle 1, Day 12, 2 h postdose |
837.8
(496.95)
|
| Cycle 1, Day 15, 1 h postdose |
362.3
(246.81)
|
| Cycle 1, Day 15, 2 h postdose |
470.6
(296.31)
|
| Cycle 1, Day 15, 4 h postdose |
575.5
(422.33)
|
| Cycle 1, Day 15, 8 h postdose |
474.2
(499.30)
|
| Cycle 2, Day 1, 2 h postdose |
429.1
(339.86)
|
| Cycle 3, Day 1, 2 h postdose |
348.5
(458.67)
|
| Cycle 4, Day 1, 2 h postdose |
408.5
(291.78)
|
| Cycle 5, Day 1, 2 h postdose |
186.3
(188.34)
|
| Cycle 6, Day 1, 2 h postdose |
80.0
(77.57)
|
| Cycle 7, Day 1, 2 h postdose |
151.3
(155.60)
|
| Cycle 8, Day 1, 2 h postdose |
418.6
(357.18)
|
| Cycle 9, Day 1, 2 h postdose |
83.1
(NA)
|
| Title | Number of Participants Who Died |
|---|---|
| Description | The number of participants who died while on study treatment and the number of participants who died during the 30-day follow-up (30 days post last dose) are reported. |
| Time Frame | Baseline through study completion [Cycle 9 plus 30 days post last dose (21-day or 28 day cycles)] |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of study drug. |
| Arm/Group Title | Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 |
|---|---|---|---|
| Arm/Group Description | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. |
| Measure Participants | 7 | 6 | 7 |
| Death On Study, Prior To Cycle 2 Completion |
1
14.3%
|
0
0%
|
0
0%
|
| Death On Study, Post Cycle 2 Completion |
0
0%
|
1
16.7%
|
0
0%
|
| Death During 30-Day Follow-Up |
2
28.6%
|
1
16.7%
|
0
0%
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | |||
| Arm/Group Description | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D8, and D15 for two 28-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, and D9 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | LY2090314: 40 mg administered as an intravenous infusion over 60-minutes on D1, D5, D9, and D12 for two 21-day cycles. If therapeutically beneficial, participants could continue additional treatment cycles until death, disease progression or other study discontinuation criteria were met. | |||
All Cause Mortality |
||||||
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/7 (57.1%) | 5/6 (83.3%) | 6/7 (85.7%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile neutropenia | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 2/7 (28.6%) | 3 |
| Splenic infarction | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Cardiac disorders | ||||||
| Atrial fibrillation | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Cardiac ventricular disorder | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Gastrointestinal disorders | ||||||
| Ileitis | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Small intestinal obstruction | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Infections and infestations | ||||||
| Clostridial infection | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Epiglottitis | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| Lung infection | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/7 (28.6%) | 2 |
| Necrotising fasciitis | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Pneumonia fungal | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Pseudomonas infection | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Staphylococcal infection | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Infusion related reaction | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Flank pain | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Acute myeloid leukaemia | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Nervous system disorders | ||||||
| Haemorrhagic stroke | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Syncope | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Cohort 1, 40 mg LY2090314: D1, D8, D15 | Cohort 2, 40 mg LY2090314: D1, D5, D9 | Cohort 3, 40 mg LY2090314: D1, D5, D9, D12 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | 6/6 (100%) | 7/7 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/7 (14.3%) | 1 | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 1 |
| Disseminated intravascular coagulation | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Thrombocytopenia | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Cardiac disorders | ||||||
| Atrial flutter | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Left ventricular dysfunction | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Eye disorders | ||||||
| Cataract | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| Eye disorder | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Eye pain | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Halo vision | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Retinal exudates | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Vision blurred | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Vitreous detachment | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal distension | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Abdominal pain | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Abdominal pain upper | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Ascites | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Constipation | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Diarrhoea | 2/7 (28.6%) | 2 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| Dry mouth | 2/7 (28.6%) | 2 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| Dyspepsia | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| Dysphagia | 1/7 (14.3%) | 1 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| Faeces discoloured | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Gastrooesophageal reflux disease | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Gingival bleeding | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Gingival blister | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Gingival pain | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Haemorrhoids | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Mouth haemorrhage | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Nausea | 3/7 (42.9%) | 4 | 1/6 (16.7%) | 1 | 3/7 (42.9%) | 4 |
| Oral pain | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Proctalgia | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Vomiting | 1/7 (14.3%) | 1 | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 1 |
| General disorders | ||||||
| Asthenia | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Catheter site pain | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Chest discomfort | 0/7 (0%) | 0 | 2/6 (33.3%) | 3 | 0/7 (0%) | 0 |
| Chest pain | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Chills | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Cyst | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Fatigue | 3/7 (42.9%) | 3 | 1/6 (16.7%) | 1 | 2/7 (28.6%) | 2 |
| Influenza like illness | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Malaise | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Mucosal inflammation | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Nodule | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Oedema peripheral | 1/7 (14.3%) | 1 | 3/6 (50%) | 3 | 2/7 (28.6%) | 2 |
| Pyrexia | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Systemic inflammatory response syndrome | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Infections and infestations | ||||||
| Cellulitis | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Epiglottitis | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Oral candidiasis | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Paronychia | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Rhinitis | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Staphylococcal infection | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Upper respiratory tract infection | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Arthropod bite | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Contusion | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Wound | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Investigations | ||||||
| Blood creatinine increased | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| Blood fibrinogen decreased | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Electrocardiogram qt prolonged | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/7 (28.6%) | 3 |
| International normalised ratio increased | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Platelet count decreased | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Weight decreased | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 4/7 (57.1%) | 4 | 1/6 (16.7%) | 1 | 2/7 (28.6%) | 2 |
| Dehydration | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Hyperglycaemia | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 |
| Hypernatraemia | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Hypoalbuminaemia | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| Hypocalcaemia | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 0/7 (0%) | 0 |
| Hypokalaemia | 2/7 (28.6%) | 2 | 3/6 (50%) | 4 | 0/7 (0%) | 0 |
| Hypomagnesaemia | 0/7 (0%) | 0 | 2/6 (33.3%) | 3 | 0/7 (0%) | 0 |
| Hyponatraemia | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Hypophosphataemia | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Back pain | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Bone pain | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Joint stiffness | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Muscle spasms | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Musculoskeletal chest pain | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Pain in extremity | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Nervous system disorders | ||||||
| Dizziness | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Dysgeusia | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| Headache | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/7 (14.3%) | 1 |
| Paraesthesia | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Sinus headache | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Psychiatric disorders | ||||||
| Anxiety | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Confusional state | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Depression | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Insomnia | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Dysuria | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Haematuria | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Renal failure | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Scrotal pain | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/2 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory failure | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Cough | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 2/7 (28.6%) | 3 |
| Dyspnoea | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Dyspnoea exertional | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Epistaxis | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Nasal congestion | 0/7 (0%) | 0 | 3/6 (50%) | 3 | 0/7 (0%) | 0 |
| Oropharyngeal discomfort | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Oropharyngeal pain | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/7 (0%) | 0 |
| Pleuritic pain | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Productive cough | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Respiratory failure | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Rhinitis allergic | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Tachypnoea | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Wheezing | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Dry skin | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Hyperhidrosis | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Night sweats | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Petechiae | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Pruritus | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Pruritus generalised | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Rash maculo-papular | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Rash papular | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Rash pruritic | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Skin mass | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/7 (14.3%) | 1 |
| Skin ulcer | 0/7 (0%) | 0 | 2/6 (33.3%) | 3 | 0/7 (0%) | 0 |
| Vascular disorders | ||||||
| Deep vein thrombosis | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Embolism | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/7 (0%) | 0 |
| Haematoma | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 0/7 (0%) | 0 |
| Hypotension | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 1/7 (14.3%) | 1 |
Limitations/Caveats
An interim data review was performed after 6 participants in the safety lead-in completed 1 cycle of therapy. Based on the interim safety results, the expansion cohort was not opened to enrollment.
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 |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01214603
Other Study ID Numbers:
- 13370
- I2H-MC-JWYB
First Posted:
Oct 5, 2010
Last Update Posted:
Nov 19, 2018
Last Verified:
Oct 1, 2018