A Study of LY2584702 in Participants With Advanced Cancer
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT01394003
Collaborator
(none)
34
2
1
28.9
17
0.6
Study Details
Study Description
Brief Summary
The main purpose of this trial is to determine a recommended Phase 2 dose of LY2584702 that may be safely administered to participants with advanced/metastatic cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
34 participants
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of LY2584702 in Patient With Advanced or Metastatic Cancer
Study Start Date
:
Nov 1, 2008
Actual Primary Completion Date
:
Apr 1, 2011
Actual Study Completion Date
:
Apr 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LY2584702 Oral dose escalation starting at 25 milligrams (mg), daily for 28 day cycles in Part A; oral dose escalation starting at 50 mg, twice daily for 28 day cycles in Part B; oral dose with schedule determined by Parts A and B will be administered in Part C (dose confirmation). Part A: Participants received 25 mg, 50 mg, 100 mg and 200 mg once daily (QD) and 300 mg twice daily (BID) of LY2584702 capsule, for a 28-day cycle during Part A of the study until the criteria for maximum tolerated dose (MTD) were met. Part B: Participants received 50 mg, 75 mg and 100 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until the criteria for maximum tolerated dose (MTD) were met. |
Drug: LY2584702
administered orally
|
Outcome Measures
Primary Outcome Measures
- Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD) [Parts A and B, Baseline through Cycle 1 (1 cycle=28 days)]
Based on the maximum tolerated dose (MTD): highest dose where <33% participants experienced a dose-limiting toxicity (DLT). DLTs were adverse events (AEs) during Cycle 1 that met any 1 of the following criteria using National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE) grading: any ≥Grade 3 nonhematological toxicity (except nausea/vomiting, diarrhea or hypophosphatemia without maximal symptomatic/prophylactic treatment) that was not related to study disease, any ≥Grade 3 thrombocytopenia with bleeding, any Grade 4 hematological toxicity of >5 days duration or any febrile neutropenia. Investigators, together with the sponsor, could declare a DLT during Cycle 1 if a participant experienced increasing toxicity and it was clear that further treatment would expose the participant to excessive risk. The MTD was below the level required for efficacy, therefore, the study was terminated early and the recommended Phase 2 dose was not calculated.
Secondary Outcome Measures
- Pharmacokinetics, Maximum Plasma Concentration (Cmax) [Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, 8 hours postdose)]
Cmax results on Day 1 and on Day 8 (steady state) are reported.
- Number of Participants With Tumor Response [Parts A and B, Baseline through study completion [up to Cycle 10 (1 cycle=28 days)]]
Tumor response was defined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria. Complete Response (CR) was the disappearance of all target and non-target lesions and normalization of tumor marker levels of non-target lesions; Partial Response (PR) was at least a 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) was at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions; Stable Disease (SD) was small changes that did not meet above criteria including persistence of 1 or more non-target lesion(s).
- Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing [Part A, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose)]
Results for AUC from time 0 to infinity [AUC(0-inf)] and AUC from time 0 to 24 hours [AUC(0-24)] on Day 1 and Day 8 (steady state) are reported for participants on a QD LY2584702 dosing regimen.
- Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing [Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose)]
Results for AUC from time 0 to infinity [AUC(0-inf)] and AUC from time 0 to 12 hours [AUC(0-12)] on Day 1 and Day 8 (steady state) are reported for participants with a BID LY2584702 dosing regimen.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Have histological or cytological evidence of a diagnosis of advanced and/or metastatic cancer (solid tumors) that is refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists
-
Have the presence of disease amenable to efficacy assessment as defined by the Response Evaluation Criteria in Solid Tumors. Participants who have advanced non-measurable disease with elevation of a validated tumor marker may be eligible, if discussed and agreed upon by the investigator and the sponsor
-
Participants entering Part C of the study must have a tumor that is safely amenable to 2 biopsies (one pre-treatment and one on-treatment biopsy for the same tumor). Participants in Part C of the study must agree to biopsy procedures at time of consent
-
Have adequate hematologic, renal, and hepatic organ function
-
Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
-
Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy (with the exception of continuing gonadotropic releasing hormone (GnRH) agonist therapy for participants with prostate cancer, or anti-estrogen therapy [for example, an aromatase inhibitor] for participants with breast cancer), or other investigational therapy for at least 3 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy
-
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 child bearing potential must have had a negative 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 12 weeks
-
Are able to swallow capsules
Exclusion Criteria:
-
Have received treatment within 3 weeks of the initial dose of study drug with a drug that has not received regulatory approval for any indication
-
Have 1 or more serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study.
-
Have symptomatic central nervous system (CNS) malignancy or metastasis. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastasis is not required
-
Have hematologic malignancies, or lymphoma
-
Females who are pregnant or lactating
-
Have a second primary malignancy that, in the judgement of the investigator and sponsor, may affect the interpretation of results
-
Have bleeding diathesis
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. | Santa Monica | California | United States | |
| 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. | San Antonio | Texas | United States |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-817-285-4559) or 1-317-615-4559 Mon-Fri 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
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01394003
Other Study ID Numbers:
- 12451
- I3G-MC-JGCA
First Posted:
Jul 14, 2011
Last Update Posted:
Jan 18, 2019
Last Verified:
Aug 1, 2018
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Parts A and B of the study were conducted to determine the dose and dosing schedule to be used in Part C (dose confirmation phase). The decision to initiate Part B was based on the safety, pharmacokinetic, and pharmacodynamic results in Part A. The study was terminated prior to participant enrollment in Part C of the study. |
| Arm/Group Title | 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 25 milligrams (mg) of LY2584702 orally as a capsule, once daily (QD) for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 200 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 75 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 300 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. |
| Period Title: Overall Study | ||||||||
| STARTED | 3 | 8 | 3 | 6 | 3 | 3 | 6 | 2 |
| Received at Least 1 Dose of Study Drug | 3 | 8 | 3 | 6 | 3 | 3 | 6 | 2 |
| COMPLETED | 3 | 8 | 3 | 6 | 3 | 3 | 6 | 2 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID | Total |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 25 milligrams (mg) of LY2584702 orally as a capsule, once daily (QD) for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 200 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 75 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 300 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Total of all reporting groups |
| Overall Participants | 3 | 8 | 3 | 6 | 3 | 3 | 6 | 2 | 34 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||
| Mean (Standard Deviation) [years] |
66.0
(15.39)
|
61.0
(8.65)
|
66.0
(4.58)
|
62.7
(15.40)
|
59.7
(16.65)
|
69.3
(3.79)
|
60.7
(9.14)
|
40.5
(20.51)
|
61.5
(12.13)
|
| Sex: Female, Male (Count of Participants) | |||||||||
| Female |
3
100%
|
5
62.5%
|
3
100%
|
3
50%
|
0
0%
|
0
0%
|
5
83.3%
|
2
100%
|
21
61.8%
|
| Male |
0
0%
|
3
37.5%
|
0
0%
|
3
50%
|
3
100%
|
3
100%
|
1
16.7%
|
0
0%
|
13
38.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||||
| Hispanic or Latino |
1
33.3%
|
1
12.5%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
1
16.7%
|
1
50%
|
5
14.7%
|
| Not Hispanic or Latino |
2
66.7%
|
7
87.5%
|
3
100%
|
6
100%
|
3
100%
|
2
66.7%
|
5
83.3%
|
1
50%
|
29
85.3%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||||
| Asian |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
2
5.9%
|
| Black |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
2.9%
|
| White |
3
100%
|
8
100%
|
2
66.7%
|
6
100%
|
3
100%
|
2
66.7%
|
5
83.3%
|
2
100%
|
31
91.2%
|
| Region of Enrollment (Count of Participants) | |||||||||
| United States |
3
100%
|
8
100%
|
3
100%
|
6
100%
|
3
100%
|
3
100%
|
6
100%
|
2
100%
|
34
100%
|
Outcome Measures
| Title | Recommended Dose for Phase 2 Studies/Maximum Tolerated Dose (MTD) |
|---|---|
| Description | Based on the maximum tolerated dose (MTD): highest dose where <33% participants experienced a dose-limiting toxicity (DLT). DLTs were adverse events (AEs) during Cycle 1 that met any 1 of the following criteria using National Cancer Institute's (NCI) Common Terminology Criteria for AEs (CTCAE) grading: any ≥Grade 3 nonhematological toxicity (except nausea/vomiting, diarrhea or hypophosphatemia without maximal symptomatic/prophylactic treatment) that was not related to study disease, any ≥Grade 3 thrombocytopenia with bleeding, any Grade 4 hematological toxicity of >5 days duration or any febrile neutropenia. Investigators, together with the sponsor, could declare a DLT during Cycle 1 if a participant experienced increasing toxicity and it was clear that further treatment would expose the participant to excessive risk. The MTD was below the level required for efficacy, therefore, the study was terminated early and the recommended Phase 2 dose was not calculated. |
| Time Frame | Parts A and B, Baseline through Cycle 1 (1 cycle=28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug. |
| Arm/Group Title | Part A | Part B |
|---|---|---|
| Arm/Group Description | Participants received 25 mg, 50 mg, 100 mg and 200 mg once daily (QD) and 300 mg twice daily (BID) of LY2584702 capsule, for a 28-day cycle during Part A of the study until the criteria for maximum tolerated dose (MTD) were met. | Participants received 50 mg, 75 mg and 100 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until the criteria for maximum tolerated dose (MTD) were met. |
| Measure Participants | 22 | 12 |
| Number [milligrams (mg)] |
NA
|
NA
|
| Title | Pharmacokinetics, Maximum Plasma Concentration (Cmax) |
|---|---|
| Description | Cmax results on Day 1 and on Day 8 (steady state) are reported. |
| Time Frame | Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, 8 hours postdose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug and had evaluable Cmax data. In 300 mg LY2584702 BID group data was not analyzed for Cmax day 8 due to insufficient participants at the specified time point. |
| Arm/Group Title | 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 25 milligrams (mg) of LY2584702 orally as a capsule, once daily (QD) for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 200 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 75 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 300 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. |
| Measure Participants | 3 | 8 | 3 | 6 | 3 | 3 | 5 | 2 |
| Day 1 |
425.79
(42.2)
|
970.28
(62.3)
|
446.43
(17.0)
|
1428.74
(66.7)
|
522.47
(87.9)
|
1358.19
(57.1)
|
1563.55
(56.5)
|
3409.5
(65.0)
|
| Day 8 |
442.36
(49.2)
|
991.74
(78.9)
|
1518.04
(60.6)
|
1540.91
(78.9)
|
841.58
(43.3)
|
1347.12
(54.3)
|
2529.26
(44.8)
|
| Title | Number of Participants With Tumor Response |
|---|---|
| Description | Tumor response was defined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0) criteria. Complete Response (CR) was the disappearance of all target and non-target lesions and normalization of tumor marker levels of non-target lesions; Partial Response (PR) was at least a 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) was at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions; Stable Disease (SD) was small changes that did not meet above criteria including persistence of 1 or more non-target lesion(s). |
| Time Frame | Parts A and B, Baseline through study completion [up to Cycle 10 (1 cycle=28 days)] |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug. |
| Arm/Group Title | 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received 25 milligrams (mg) of LY2584702 orally as a capsule, once daily (QD) for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 200 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 75 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 300 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. |
| Measure Participants | 3 | 8 | 3 | 6 | 3 | 3 | 6 | 2 |
| Complete Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Partial Response |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Stable Disease |
0
0%
|
2
25%
|
0
0%
|
0
0%
|
1
33.3%
|
2
66.7%
|
0
0%
|
0
0%
|
| Progressive Disease |
2
66.7%
|
2
25%
|
2
66.7%
|
4
66.7%
|
2
66.7%
|
1
33.3%
|
1
16.7%
|
0
0%
|
| Title | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Once Daily (QD) LY2584702 Dosing |
|---|---|
| Description | Results for AUC from time 0 to infinity [AUC(0-inf)] and AUC from time 0 to 24 hours [AUC(0-24)] on Day 1 and Day 8 (steady state) are reported for participants on a QD LY2584702 dosing regimen. |
| Time Frame | Part A, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug [QD dosing regimen (Part A)]. |
| Arm/Group Title | 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD |
|---|---|---|---|---|
| Arm/Group Description | Participants received 25 milligrams (mg) of LY2584702 orally as a capsule, once daily (QD) for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 200 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. |
| Measure Participants | 3 | 8 | 3 | 6 |
| AUC(0-inf), Day 1 |
4831.85
(59.3)
|
7968.44
(41.8)
|
4698.94
(7.5)
|
20147.91
(56.9)
|
| AUC(0-24), Day 1 |
3918.51
(44.0)
|
7505.27
(43.0)
|
3885.40
(18.8)
|
14206.13
(60.9)
|
| AUC(0-24), Day 8 |
2310.93
(36.5)
|
5432.02
(85.1)
|
6106.05
(57.9)
|
8731.94
(78.5)
|
| Title | Pharmacokinetics, Area Under the Concentration-Time Curve (AUC) With Twice Daily (BID) LY2584702 Dosing |
|---|---|
| Description | Results for AUC from time 0 to infinity [AUC(0-inf)] and AUC from time 0 to 12 hours [AUC(0-12)] on Day 1 and Day 8 (steady state) are reported for participants with a BID LY2584702 dosing regimen. |
| Time Frame | Parts A and B, Cycle 1: Day 1 and Day 8 (predose, 0.5, 1, 2, 3, 5, and 8 hours postdose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug [BID dosing regimen (Part A or B)] and had evaluable AUC data. In 300 mg LY2584702 BID group data was not analyzed for AUC(0-12) day 8 due to insufficient participants at the specified time point. |
| Arm/Group Title | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received 50 milligrams (mg) LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 75 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 300 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. |
| Measure Participants | 3 | 3 | 5 | 2 |
| AUC(0-inf), Day 1 |
3922.09
(70.0)
|
12381.00
(70.0)
|
11625.53
(59.3)
|
30897
(NA)
|
| AUC(0-12), Day 1 |
2461.26
(83.9)
|
6389.44
(57.5)
|
6856.58
(53.4)
|
13084.5
(90.5)
|
| AUC(0-12), Day 8 |
4470.57
(39.4)
|
6669.70
(46.3)
|
13718.79
(53.3)
|
Adverse Events
| Time Frame | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Study-specific clinical outcomes due to progressive disease were not considered to be a serious adverse event (SAE) unless the investigator deemed it related to the use of the study drug. | |||||||||||||||
| Arm/Group Title | 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID | ||||||||
| Arm/Group Description | Participants received 25 milligrams (mg) of LY2584702 orally as a capsule, once daily (QD) for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 200 mg LY2584702 orally as a capsule, QD for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 50 mg LY2584702 orally as a capsule, twice daily (BID) for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 75 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 100 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part B of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | Participants received 300 mg LY2584702 orally as a capsule, BID for a 28-day cycle during Part A of the study until disease progression, unacceptable toxicity, or other withdrawal criteria were met. | ||||||||
All Cause Mortality |
||||||||||||||||
| 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
| 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 2/8 (25%) | 1/3 (33.3%) | 2/6 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 3/6 (50%) | 1/2 (50%) | ||||||||
| Cardiac disorders | ||||||||||||||||
| Cardio-respiratory arrest | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal pain | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Colitis ischaemic | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Nausea | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Pancreatitis | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 2 | 1/2 (50%) | 1 |
| Vomiting | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| General disorders | ||||||||||||||||
| Pyrexia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||
| Bile duct stenosis | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Infections and infestations | ||||||||||||||||
| Appendicitis | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Urosepsis | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Investigations | ||||||||||||||||
| Blood amylase increased | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Lipase increased | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Dehydration | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Hypophosphataemia | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Back pain | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Muscular weakness | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Metastases to central nervous system | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||
| Partial seizures | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||
| Mental status changes | 1/3 (33.3%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||
| Ureteric obstruction | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Pulmonary embolism | 1/3 (33.3%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||
| 25 mg LY2584702 QD | 50 mg LY2584702 QD | 100 mg LY2584702 QD | 200 mg LY2584702 QD | 50 mg LY2584702 BID | 75 mg LY2584702 BID | 100 mg LY2584702 BID | 300 mg LY2584702 BID | |||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 7/8 (87.5%) | 2/3 (66.7%) | 5/6 (83.3%) | 3/3 (100%) | 3/3 (100%) | 6/6 (100%) | 2/2 (100%) | ||||||||
| Blood and lymphatic system disorders | ||||||||||||||||
| Anaemia | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Lymphadenopathy | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Cardiac disorders | ||||||||||||||||
| Sinus tachycardia | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Eye disorders | ||||||||||||||||
| Abnormal sensation in eye | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Cataract | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Ocular surface disease | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||
| Abdominal distension | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Abdominal pain | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Abdominal pain lower | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Abdominal pain upper | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Abdominal tenderness | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Constipation | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 0/2 (0%) | 0 |
| Diarrhoea | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 1/2 (50%) | 1 |
| Dyspepsia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/2 (0%) | 0 |
| Epigastric discomfort | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Faecal incontinence | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Haemorrhoids | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Nausea | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 3/6 (50%) | 3 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 2 | 2/6 (33.3%) | 2 | 1/2 (50%) | 1 |
| Stomatitis | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Vomiting | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 1/2 (50%) | 1 |
| General disorders | ||||||||||||||||
| Early satiety | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Fatigue | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 1/3 (33.3%) | 1 | 2/6 (33.3%) | 2 | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 3/6 (50%) | 3 | 0/2 (0%) | 0 |
| Influenza like illness | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Mucosal inflammation | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Oedema | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Oedema peripheral | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 2 | 0/2 (0%) | 0 |
| Pain | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Hepatobiliary disorders | ||||||||||||||||
| Hyperbilirubinaemia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/2 (0%) | 0 |
| Immune system disorders | ||||||||||||||||
| Seasonal allergy | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Infections and infestations | ||||||||||||||||
| Candidiasis | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Fungal infection | 0/3 (0%) | 0 | 1/8 (12.5%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Oral candidiasis | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Oral herpes | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Upper respiratory tract infection | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Urinary tract infection | 1/3 (33.3%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Investigations | ||||||||||||||||
| Lipase increased | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Weight decreased | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Weight increased | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||
| Anorexia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/6 (50%) | 3 | 1/2 (50%) | 1 |
| Dehydration | 1/3 (33.3%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Hypokalaemia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Hypomagnesaemia | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Hypophosphataemia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 0/2 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||
| Arthralgia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Back pain | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Flank pain | 1/3 (33.3%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Muscular weakness | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Musculoskeletal chest pain | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Musculoskeletal pain | 0/3 (0%) | 0 | 2/8 (25%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Myalgia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Neck pain | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Pain in extremity | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
| Tumour pain | 1/3 (33.3%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||
| Dizziness | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 1/6 (16.7%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Headache | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 2/6 (33.3%) | 2 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Memory impairment | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Peripheral motor neuropathy | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Peroneal nerve palsy | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Psychiatric disorders | ||||||||||||||||
| Anxiety | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/2 (50%) | 1 |
| Insomnia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||||
| Nocturia | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Pollakiuria | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||
| Breast pain | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Vaginal haemorrhage | 0/3 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/0 (NaN) | 0 | 0/0 (NaN) | 0 | 0/5 (0%) | 0 | 0/2 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
| Cough | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Dyspnoea | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Dyspnoea exertional | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||
| Dermal cyst | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Dry skin | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Erythema | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Nail disorder | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Pruritus | 1/3 (33.3%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Rash | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 1/3 (33.3%) | 1 | 0/6 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Skin odour abnormal | 0/3 (0%) | 0 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Vascular disorders | ||||||||||||||||
| Hot flush | 0/3 (0%) | 0 | 1/8 (12.5%) | 1 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/2 (0%) | 0 |
| Hypertension | 1/3 (33.3%) | 1 | 0/8 (0%) | 0 | 0/3 (0%) | 0 | 0/6 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/6 (16.7%) | 1 | 0/2 (0%) | 0 |
Limitations/Caveats
Part C of the study was terminated because exposure at the maximum tolerated dose (MTD) was determined to be below the level required for efficacy.
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:
NCT01394003
Other Study ID Numbers:
- 12451
- I3G-MC-JGCA
First Posted:
Jul 14, 2011
Last Update Posted:
Jan 18, 2019
Last Verified:
Aug 1, 2018