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A Study LY2228820 for Recurrent Ovarian Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01663857
Collaborator
(none)
118
Enrollment
30
Locations
4
Arms
70.3
Duration (Months)
3.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A study for women with ovarian cancer that has returned at least 6 months after platinum-based chemotherapy.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Phase 1b is unblinded and will have a small number of participants that will take LY2228820 plus gemcitabine and carboplatin to test the safety of the combination and determine a recommended dose for the Phase 2 portion.

Phase 2 will be blinded and all study participants will receive carboplatin and gemcitabine. Participants of one group will receive LY2228820, and the other group will receive placebo.

If the participant achieves at least stable disease, there is a maintenance phase following the first 6 cycles. The participant will take either LY2228820 or placebo. The participant will continue therapy until disease progression or other discontinuation criteria are fulfilled.

Study Design

Study Type:
Interventional
Actual Enrollment :
118 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38 MAPK Inhibitor, Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin for Women With Platinum-Sensitive Ovarian Cancer
Study Start Date :
Jul 1, 2012
Actual Primary Completion Date :
May 25, 2017
Actual Study Completion Date :
May 11, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1b (Cohort 1) LY2228820 200 milligrams (mg)

Cohort 1: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 milligrams per square meter (mg/m^2) administered intravenously (IV) over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3.. Cohort 1: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.

Drug: LY2228820
Administered Orally

Drug: Carboplatin
Administered IV

Drug: Gemcitabine
Administered IV
Other Names:
  • Gemzar
  • LY188011

    		•
    Experimental: Phase 1b (Cohort 2) LY2228820 300 mg

    Cohort 2: Cycles 1-6 (21 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3. Cohort 2: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.

    Drug: LY2228820
    Administered Orally

    Drug: Carboplatin
    Administered IV

    Drug: Gemcitabine
    Administered IV
    Other Names:
  • Gemzar
  • LY188011

    		•
    Experimental: Phase 2 (Arm A) LY2228820 200 mg

    Arm A: Cycles 1-6 (21 day cycles)- LY2228820 200 mg administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3. Arm A: Cycles 7+ (28 day cycles)- LY2228820 300 mg administered orally every 12 hours on days 1-14.

    Drug: LY2228820
    Administered Orally

    Drug: Carboplatin
    Administered IV

    Drug: Gemcitabine
    Administered IV
    Other Names:
  • Gemzar
  • LY188011

    		•
    Placebo Comparator: Phase 2 (Arm B) Placebo

    Arm B: Cycles 1-6 (21 day cycles)- Placebo administered orally every 12 hours on days 1-10. Gemcitabine 1000 mg/m^2 administered IV over 30 minutes on days 3 and 10. Carboplatin dose Area Under Curve (AUC) 4 (maximum dose 600 mg) administered IV over 30 minutes on day 3. Arm B: Cycle 7+ (28 day cycles)- Placebo administered orally on days 1-14 to maintain blind.

    Drug: Carboplatin
    Administered IV

    Drug: Placebo
    Administered Orally

    Drug: Gemcitabine
    Administered IV
    Other Names:
  • Gemzar
  • LY188011

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD]) [Cycle 1 (21 Days)]

      Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).

    2. Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin [Randomization to Date of Disease Progression or Death from any cause (up to 3 years)]

      PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

    Secondary Outcome Measures

    1. Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate) [Baseline to Disease Progression (up to 3 years)]

      Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.

    2. Phase 2: Overall Survival [Baseline to Date of Death from any cause (up to 5 years)]

      Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.

    3. Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820 [Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD]

      PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.

    4. Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score [Baseline, Study Completion (up to 3 years)]

      The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = "not at all" and 4 = "very much." Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Have been diagnosed with ovarian, fallopian tube, or primary peritoneal cancer

    • Have been treated one time with a platinum-based chemotherapy and your disease has come back at least six months after you completed treatment

    • Are able to swallow tablets

    • Have given written informed consent prior to any study procedures

    • Have adequate blood counts, hepatic and renal function

    • Have performance status equal to or less than 2 on Eastern Cooperative Oncology Group (ECOG) scale

    • Have negative pregnancy test, and if participant is of child bearing potential must use birth control while on study and for three months after stopping study drug

    Exclusion Criteria:

    • Have been previously treated with Gemcitabine for ovarian, fallopian tube or primary peritoneal cancer

    • Are currently enrolled or discontinued less than 14 days from another clinical trial

    • Have a history of inflammatory bowel disease (Crohn's disease or ulcerative colitis)

    • Have taken certain medications or had grapefruit juice within 7 days of initial dose of study drug, as levels of the study drug may be affected.

    • Must not be pregnant or breastfeeding.

    • Have malignancy or metastasis of the central nervous system

    • Have borderline malignancy

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 St Josephs Hospital and Medical Center Phoenix Arizona United States 85013
    2 Arizona Oncology Associates, P.C. Tucson Arizona United States 85710
    3 Sarasota Memorial Hospital Sarasota Florida United States 34239
    4 H Lee Moffitt Cancer Center Tampa Florida United States 33612
    5 Franklin Square Hospital Center Baltimore Maryland United States 21237
    6 Barnes Jewish Hospital Saint Louis Missouri United States 63110
    7 Rutgers Cancer Institute of New Jersey New Brunswick New Jersey United States 08901
    8 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
    9 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    10 SMO Sarah Cannon Research Inst. Nashville Tennessee United States 37203
    11 Texas Oncology-Baylor Charles A. Sammons Cancer Center Austin Texas United States 78731
    12 Texas Oncology-Baylor Charles A. Sammons Cancer Center Bedford Texas United States 76022
    13 Texas Oncology-Baylor Charles A. Sammons Cancer Center Dallas Texas United States 75246
    14 Texas Oncology-Baylor Charles A. Sammons Cancer Center Fort Worth Texas United States 76104
    15 Cancer Care Centers of South Texas San Antonio Texas United States 78229
    16 Texas Oncology - The Woodlands The Woodlands Texas United States 77380
    17 US Oncology The Woodlands Texas United States 77380
    18 Tyler Cancer Center Tyler Texas United States 75702
    19 Northwest Cancer Specialists PC Vancouver Washington United States 98684
    20 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Adelaide Australia 5000
    21 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Greenslopes Australia 4120
    22 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Nedlands Australia 6009
    23 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Parkville Australia 3053
    24 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Leuven Belgium 3000
    25 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Berlin Germany 10117
    26 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Essen Germany 45122
    27 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Essen Germany 45136
    28 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Greifswald Germany 17489
    29 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. Mainz Germany 55131
    30 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. München Germany 81675

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9am-5pm Eastern time *UTC/GMT-5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01663857
    Other Study ID Numbers:
    • 12517
    • I1D-MC-JIAE
    First Posted:
    Aug 13, 2012
    Last Update Posted:
    Sep 11, 2019
    Last Verified:
    Aug 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Additional relevant MeSH terms:
    Ovarian Neoplasms
    Carcinoma, Ovarian Epithelial
    Fallopian Tube Neoplasms
    Gemcitabine
    Carboplatin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail Participants in Phase 1b are considered to have completed the study if they experience a dose-limiting toxicity or completed the Pharmacokinetic (PK) sampling set. Participants in Phase 2 are considered to have completed if they die due to any cause or who are alive and on study at conclusion, but are off treatment.
    Arm/Group Title Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
    Arm/Group Description Cohort 1:LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 of a 21-day cycle. Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+). Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Cohort 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+). Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+) Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)
    Period Title: Overall Study
    STARTED 6 2 58 52
    Received at Least One Dose of Study Drug 6 2 58 52
    COMPLETED 6 1 48 48
    NOT COMPLETED 0 1 10 4

    Baseline Characteristics

    Arm/Group Title Phase 1b: Cohort 1: LY2228820 +Gemcitabine+Carboplatin Phase 1b: Cohort 2: LY2228820 +Gemcitabine+Carboplatin Arm A: LY2228820 + Gemcitabine + Carboplatin Arm B Placebo + Gemcitabine +Carboplatin Total
    Arm/Group Description Cohort 1:LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10. Carboplatin area under the concentration curve administered intravenously (IV) over 30 minutes (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3. Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6). Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m2 administered IV over 30 min on Days 3 and 10. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3. Cohort 2:LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+). Arm A:LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3. Arm A:LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+). Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle (Cycles 1-6). Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+). Total of all reporting groups
    Overall Participants 6 2 58 52 118
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    62.7
    (6.8)
    65.0
    (5.7)
    60.9
    (10.4)
    62.2
    (9.2)
    61.6
    (9.6)
    Sex: Female, Male (Count of Participants)
    Female
    6
    100%
    2
    100%
    58
    100%
    52
    100%
    118
    100%
    Male
    0
    0%
    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%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    2
    3.8%
    2
    1.7%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    1
    50%
    1
    1.7%
    0
    0%
    2
    1.7%
    White
    6
    100%
    1
    50%
    57
    98.3%
    49
    94.2%
    113
    95.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    1
    1.9%
    1
    0.8%
    Region of Enrollment (Count of Participants)
    Belgium
    0
    0%
    0
    0%
    11
    19%
    9
    17.3%
    20
    16.9%
    United States
    5
    83.3%
    2
    100%
    30
    51.7%
    25
    48.1%
    62
    52.5%
    Australia
    0
    0%
    0
    0%
    4
    6.9%
    6
    11.5%
    10
    8.5%
    Germany
    1
    16.7%
    0
    0%
    13
    22.4%
    12
    23.1%
    26
    22%
    Maintenance Therapy as a Part of or After a First Line Platinum Regimen (Count of Participants)
    Received Maintenance Therapy
    7
    116.7%
    7
    350%
    14
    24.1%
    Did Not Receive Maintenance Therapy
    15
    250%
    15
    750%
    30
    51.7%
    Data Missing or Not Collected
    36
    600%
    30
    1500%
    66
    113.8%

    Outcome Measures

    1. Primary Outcome
    Title Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])
    Description Recommended Phase 2 dose of LY2228820 that could be safely administered in combination with gemcitabine and carboplatin based on defined dose limiting toxicities (DLT) assessment and MTD definition. The MTD is defined as the highest dose level at which no more than 33% of patients experience a DLT during Cycle 1 that does not exceed the single-agent MTD for LY2228820 (300 mg Q12H).
    Time Frame Cycle 1 (21 Days)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug in Phase 1b.
    Arm/Group Title LY2228820 + Gemcitabine + Carboplatin
    Arm/Group Description Cohort 1 : LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6) Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3 Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 Cohort 1 and 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)
    Measure Participants 8
    Number [milligrams (mg)]
    200
    2. Primary Outcome
    Title Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin
    Description PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
    Time Frame Randomization to Date of Disease Progression or Death from any cause (up to 3 years)

    Outcome Measure Data

    Analysis Population Description
    All participants in Phase 2 who received at least one dose of study drug.
    Arm/Group Title LY2228820 + Gemcitabine +Carboplatin Placebo + Gemcitabine + Carboplatin
    Arm/Group Description Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of 21-day cycles. Gemcitabine 1000 mg/m2 IV over 30 min on Days 3 and 10 of 21-day cycles. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of 21-day cycles. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+) Arm B: Placebo orally every 12 hrs. on Days 1-10 of 21-day cycles. Gemcitabine 1000 mg/m2 IV over 30 min on Days 3 and 10 of 21-day cycles. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. n Day 3 of 21-day cycles. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)
    Measure Participants 58 52
    Median (90% Confidence Interval) [months]
    10.25
    8.44
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LY2228820 + Gemcitabine + Carboplatin, Placebo + Gemcitabine + Carboplatin
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4
    Comments
    Method Log Rank
    Comments
    3. Secondary Outcome
    Title Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)
    Description Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD.
    Time Frame Baseline to Disease Progression (up to 3 years)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least one dose of study drug in Phase 2.
    Arm/Group Title LY2228820 + Gemcitabine +Carboplatin Placebo + Gemcitabine + Carboplatin
    Arm/Group Description Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min.(+ 15 min.) on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+). Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)
    Measure Participants 58 52
    Number [percentage of participants]
    46.6
    776.7%
    46.2
    2310%
    4. Secondary Outcome
    Title Phase 2: Overall Survival
    Description Data presented are the median overall survival in months for participants in the Phase 2 treatment arms.
    Time Frame Baseline to Date of Death from any cause (up to 5 years)

    Outcome Measure Data

    Analysis Population Description
    All participants in Phase 2 who received at least one dose of drug.
    Arm/Group Title LY2228820 + Gemcitabine +Carboplatin Placebo + Gemcitabine + Carboplatin
    Arm/Group Description Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+). Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28-day cycle (Cycles 7+)
    Measure Participants 58 52
    Median (90% Confidence Interval) [months]
    29.17
    25.10
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection LY2228820 + Gemcitabine + Carboplatin, Placebo + Gemcitabine + Carboplatin
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4686
    Comments
    Method Log Rank
    Comments
    5. Secondary Outcome
    Title Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820
    Description PK parameters after administration of LY2228820 for both Phase 1b and Phase 2.
    Time Frame Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD

    Outcome Measure Data

    Analysis Population Description
    All participants in Phase 1b and Phase 2 who received at least one dose of study drug and had evaluable PK data.
    Arm/Group Title 200 mg LY2228820 300 mg LY2228820
    Arm/Group Description Phase 1b (Cohort 1) and Phase 2 (Arm A): LY2228820 200 mg administered orally every 12 hours on Days 1-10, Cycles 1-6 of a 21 day cycle. . Phase 1b (Cohort 2) and Phase 2 (Arm A) in the maintenance portion with LY2228820 300 mg administered orally every 12 hours on Days 1-14 Cycle 7+ of a 28-day cycle.
    Measure Participants 13 10
    Cycle 1 Day 1
    3470
    (91)
    3560
    (1)
    Cycle 1 Day 3
    3170
    (22)
    Cycle 1 Day 10
    4270
    (62)
    9350
    (NA)
    Cycle 2 Day 10
    3270
    (38)
    3490
    (NA)
    Cycle 7 Day 3
    7230
    (72)
    6. Secondary Outcome
    Title Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score
    Description The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = "not at all" and 4 = "very much." Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life.
    Time Frame Baseline, Study Completion (up to 3 years)

    Outcome Measure Data

    Analysis Population Description
    All participants in Phase 2 who received at least one dose of study drug and had at least one post baseline assessment.
    Arm/Group Title LY2228820 + Gemcitabine +Carboplatin Placebo + Gemcitabine + Carboplatin
    Arm/Group Description Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day. Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+) Arm B: Placebo orally every 12 hrs. on Days 1-10 of a 21-day cycle. Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 of a 21-day cycle. Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 of a 21-day cycle. Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)
    Measure Participants 58 52
    Mean (Standard Deviation) [units on a scale]
    -0.6
    (21.14)
    -8.9
    (19.92)

    Adverse Events

    Time Frame Up to 4.5 years
    Adverse Event Reporting Description All participants who received at least one dose of drug.
    Arm/Group Title Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
    Arm/Group Description Cohort 1: LY2228820 200 milligrams (mg) administered orally every 12 hours (hr) on Days 1-10 of a 21-day cycle (Cycles 1-6) Gemcitabine 1000 mg per square meter (m2) administered intravenously (IV) over 30 minutes (min) on Days 3 and 10 Carboplatin area under the concentration curve (AUC) 4 (maximum dose 600mg) IV over 30 min. on Day 3 Cohort 1: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+) Cohort 2: LY2228820 300 mg administered orally every 12 hr. on Days 1-10 Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 Cohort 2: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+) Arm A: LY2228820 200 mg orally every 12 hr. on Days 1-10 Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 Arm A: LY2228820 300 mg orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+) Arm B: Placebo orally every 12 hrs. on Days 1-10 Gemcitabine 1000 mg/m2 IV over 30 min. on Days 3 and 10 Carboplatin AUC 4 (maximum dose 600mg) IV over 30 min. on Day 3 Arm B: Placebo orally every 12 hr. on Days 1-14 of a 28 day cycle (Cycles 7+)
    All Cause Mortality
    Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/6 (50%) 1/2 (50%) 30/58 (51.7%) 31/52 (59.6%)
    Serious Adverse Events
    Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/6 (50%) 1/2 (50%) 26/58 (44.8%) 12/52 (23.1%)
    Blood and lymphatic system disorders
    Anaemia 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 5 0/52 (0%) 0
    Febrile neutropenia 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Leukopenia 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Neutropenia 1/6 (16.7%) 1 0/2 (0%) 0 1/58 (1.7%) 2 0/52 (0%) 0
    Thrombocytopenia 0/6 (0%) 0 0/2 (0%) 0 5/58 (8.6%) 7 0/52 (0%) 0
    Gastrointestinal disorders
    Abdominal distension 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Abdominal pain 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 4 0/52 (0%) 0
    Abdominal pain upper 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 1/52 (1.9%) 1
    Ascites 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 3 0/52 (0%) 0
    Constipation 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 3 1/52 (1.9%) 1
    Diarrhoea 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 2 0/52 (0%) 0
    Ileus 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 2 0/52 (0%) 0
    Nausea 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 5 2/52 (3.8%) 2
    Small intestinal obstruction 1/6 (16.7%) 3 0/2 (0%) 0 2/58 (3.4%) 2 1/52 (1.9%) 1
    Subileus 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 1/52 (1.9%) 1
    Vomiting 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 6 2/52 (3.8%) 2
    General disorders
    General physical health deterioration 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 2 0/52 (0%) 0
    Malaise 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Pyrexia 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 2 1/52 (1.9%) 1
    Hepatobiliary disorders
    Cholecystitis 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Immune system disorders
    Anaphylactic reaction 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Infections and infestations
    Abscess 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Appendicitis 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Bacteraemia 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Clostridium difficile infection 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Erysipelas 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 3 0/52 (0%) 0
    Gastroenteritis 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Lung infection 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 2 1/52 (1.9%) 1
    Pelvic infection 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Pneumonia 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 2 1/52 (1.9%) 1
    Pyelonephritis acute 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Sepsis 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Ureteritis 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Urinary tract infection 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Injury, poisoning and procedural complications
    Cervical vertebral fracture 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Fall 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Infusion related reaction 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Thermal burn 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Urostomy complication 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Aspartate aminotransferase increased 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Nuclear magnetic resonance imaging abdominal abnormal 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Platelet count decreased 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 1/52 (1.9%) 1
    Metabolism and nutrition disorders
    Hypokalaemia 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 1/52 (1.9%) 1
    Hypophosphataemia 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Musculoskeletal and connective tissue disorders
    Flank pain 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Joint effusion 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Nervous system disorders
    Dizziness 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Headache 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Presyncope 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Syncope 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Renal and urinary disorders
    Acute kidney injury 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 2 0/52 (0%) 0
    Pleural effusion 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Pneumonitis 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Skin and subcutaneous tissue disorders
    Drug reaction with eosinophilia and systemic symptoms 0/6 (0%) 0 1/2 (50%) 1 0/58 (0%) 0 0/52 (0%) 0
    Rash maculo-papular 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Other (Not Including Serious) Adverse Events
    Phase 1b: Cohort 1: LY2228820 + Gemcitabine + Carboplatin Phase 1b: Cohort 2: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm A: LY2228820 + Gemcitabine + Carboplatin Phase 2: Arm B: Placebo + Gemcitabine + Carboplatin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 2/2 (100%) 58/58 (100%) 52/52 (100%)
    Blood and lymphatic system disorders
    Anaemia 5/6 (83.3%) 8 1/2 (50%) 4 32/58 (55.2%) 91 25/52 (48.1%) 73
    Increased tendency to bruise 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 3 2/52 (3.8%) 2
    Leukocytosis 0/6 (0%) 0 0/2 (0%) 0 5/58 (8.6%) 8 0/52 (0%) 0
    Leukopenia 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 3 3/52 (5.8%) 4
    Neutropenia 5/6 (83.3%) 24 2/2 (100%) 4 26/58 (44.8%) 72 26/52 (50%) 74
    Thrombocytopenia 4/6 (66.7%) 9 0/2 (0%) 0 17/58 (29.3%) 40 14/52 (26.9%) 47
    Cardiac disorders
    Palpitations 0/6 (0%) 0 0/2 (0%) 0 6/58 (10.3%) 6 8/52 (15.4%) 9
    Sinus bradycardia 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Ear and labyrinth disorders
    Tinnitus 0/6 (0%) 0 0/2 (0%) 0 4/58 (6.9%) 4 2/52 (3.8%) 2
    Vertigo 2/6 (33.3%) 2 0/2 (0%) 0 2/58 (3.4%) 2 2/52 (3.8%) 4
    Eye disorders
    Glaucoma 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Vision blurred 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 3 2/52 (3.8%) 2
    Visual impairment 1/6 (16.7%) 1 0/2 (0%) 0 1/58 (1.7%) 1 3/52 (5.8%) 3
    Gastrointestinal disorders
    Abdominal discomfort 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 3/52 (5.8%) 5
    Abdominal distension 0/6 (0%) 0 1/2 (50%) 1 6/58 (10.3%) 6 12/52 (23.1%) 13
    Abdominal pain 1/6 (16.7%) 1 0/2 (0%) 0 12/58 (20.7%) 13 8/52 (15.4%) 9
    Abdominal pain upper 0/6 (0%) 0 0/2 (0%) 0 5/58 (8.6%) 5 5/52 (9.6%) 7
    Anal incontinence 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Constipation 2/6 (33.3%) 5 1/2 (50%) 1 23/58 (39.7%) 31 22/52 (42.3%) 24
    Diarrhoea 4/6 (66.7%) 5 1/2 (50%) 1 23/58 (39.7%) 40 14/52 (26.9%) 18
    Dry mouth 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 2 4/52 (7.7%) 4
    Dyspepsia 1/6 (16.7%) 1 0/2 (0%) 0 3/58 (5.2%) 3 1/52 (1.9%) 1
    Dysphagia 1/6 (16.7%) 2 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Gastrooesophageal reflux disease 0/6 (0%) 0 1/2 (50%) 1 3/58 (5.2%) 3 4/52 (7.7%) 4
    Mouth ulceration 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 2 3/52 (5.8%) 4
    Nausea 4/6 (66.7%) 8 0/2 (0%) 0 31/58 (53.4%) 39 33/52 (63.5%) 50
    Rectal haemorrhage 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 4/52 (7.7%) 5
    Stomatitis 2/6 (33.3%) 2 0/2 (0%) 0 9/58 (15.5%) 10 10/52 (19.2%) 11
    Vomiting 3/6 (50%) 3 0/2 (0%) 0 17/58 (29.3%) 23 12/52 (23.1%) 12
    General disorders
    Chills 1/6 (16.7%) 1 0/2 (0%) 0 1/58 (1.7%) 1 4/52 (7.7%) 5
    Fatigue 5/6 (83.3%) 11 0/2 (0%) 0 40/58 (69%) 50 38/52 (73.1%) 48
    Oedema peripheral 0/6 (0%) 0 0/2 (0%) 0 7/58 (12.1%) 9 7/52 (13.5%) 8
    Peripheral swelling 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 3/52 (5.8%) 3
    Pyrexia 1/6 (16.7%) 1 0/2 (0%) 0 8/58 (13.8%) 9 6/52 (11.5%) 7
    Immune system disorders
    Drug hypersensitivity 0/6 (0%) 0 0/2 (0%) 0 5/58 (8.6%) 7 5/52 (9.6%) 5
    Infections and infestations
    Bronchitis 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 2 3/52 (5.8%) 3
    Cystitis 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 3 0/52 (0%) 0
    Fungal skin infection 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Nasopharyngitis 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 2 4/52 (7.7%) 4
    Pneumonia 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Sinusitis 3/6 (50%) 4 0/2 (0%) 0 1/58 (1.7%) 1 2/52 (3.8%) 2
    Upper respiratory tract infection 0/6 (0%) 0 0/2 (0%) 0 5/58 (8.6%) 6 3/52 (5.8%) 3
    Urinary tract infection 1/6 (16.7%) 1 0/2 (0%) 0 8/58 (13.8%) 14 7/52 (13.5%) 10
    Injury, poisoning and procedural complications
    Infusion related reaction 2/6 (33.3%) 3 0/2 (0%) 0 7/58 (12.1%) 8 6/52 (11.5%) 11
    Wrist fracture 1/6 (16.7%) 2 0/2 (0%) 0 0/58 (0%) 0 1/52 (1.9%) 1
    Investigations
    Alanine aminotransferase increased 2/6 (33.3%) 5 1/2 (50%) 2 25/58 (43.1%) 42 13/52 (25%) 35
    Aspartate aminotransferase increased 3/6 (50%) 5 0/2 (0%) 0 17/58 (29.3%) 28 10/52 (19.2%) 22
    Blood alkaline phosphatase increased 1/6 (16.7%) 2 0/2 (0%) 0 9/58 (15.5%) 12 7/52 (13.5%) 7
    Blood creatinine increased 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 2 1/52 (1.9%) 1
    Blood urea increased 0/6 (0%) 0 1/2 (50%) 1 0/58 (0%) 0 0/52 (0%) 0
    Ejection fraction decreased 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Haemoglobin decreased 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 2 3/52 (5.8%) 4
    Lymphocyte count decreased 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 3 3/52 (5.8%) 5
    Neutrophil count decreased 0/6 (0%) 0 1/2 (50%) 1 26/58 (44.8%) 76 29/52 (55.8%) 92
    Platelet count decreased 1/6 (16.7%) 6 1/2 (50%) 2 21/58 (36.2%) 53 20/52 (38.5%) 66
    Weight decreased 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 2 3/52 (5.8%) 5
    White blood cell count decreased 3/6 (50%) 12 0/2 (0%) 0 20/58 (34.5%) 47 19/52 (36.5%) 55
    Metabolism and nutrition disorders
    Decreased appetite 3/6 (50%) 3 0/2 (0%) 0 14/58 (24.1%) 15 12/52 (23.1%) 13
    Dehydration 1/6 (16.7%) 1 0/2 (0%) 0 1/58 (1.7%) 1 1/52 (1.9%) 1
    Hyperglycaemia 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 2 2/52 (3.8%) 2
    Hyperkalaemia 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 4 3/52 (5.8%) 3
    Hyperuricaemia 0/6 (0%) 0 1/2 (50%) 1 2/58 (3.4%) 2 0/52 (0%) 0
    Hypocalcaemia 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 4 4/52 (7.7%) 4
    Hypokalaemia 2/6 (33.3%) 2 0/2 (0%) 0 3/58 (5.2%) 5 4/52 (7.7%) 7
    Hypomagnesaemia 0/6 (0%) 0 1/2 (50%) 1 7/58 (12.1%) 11 5/52 (9.6%) 14
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/6 (0%) 0 0/2 (0%) 0 6/58 (10.3%) 6 5/52 (9.6%) 7
    Back pain 1/6 (16.7%) 1 0/2 (0%) 0 7/58 (12.1%) 10 12/52 (23.1%) 13
    Bone pain 0/6 (0%) 0 0/2 (0%) 0 5/58 (8.6%) 5 1/52 (1.9%) 2
    Flank pain 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 2 3/52 (5.8%) 3
    Muscle spasms 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 4 6/52 (11.5%) 6
    Myalgia 0/6 (0%) 0 0/2 (0%) 0 5/58 (8.6%) 5 5/52 (9.6%) 6
    Neck pain 0/6 (0%) 0 0/2 (0%) 0 4/58 (6.9%) 4 0/52 (0%) 0
    Osteoarthritis 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Osteopenia 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Pain in extremity 1/6 (16.7%) 1 0/2 (0%) 0 4/58 (6.9%) 7 3/52 (5.8%) 3
    Nervous system disorders
    Dizziness 2/6 (33.3%) 2 0/2 (0%) 0 12/58 (20.7%) 13 9/52 (17.3%) 9
    Dysgeusia 0/6 (0%) 0 0/2 (0%) 0 5/58 (8.6%) 5 5/52 (9.6%) 5
    Headache 3/6 (50%) 4 0/2 (0%) 0 10/58 (17.2%) 10 12/52 (23.1%) 20
    Paraesthesia 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 2/52 (3.8%) 2
    Peripheral sensory neuropathy 1/6 (16.7%) 3 0/2 (0%) 0 5/58 (8.6%) 6 2/52 (3.8%) 2
    Syncope 2/6 (33.3%) 2 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Tremor 0/6 (0%) 0 0/2 (0%) 0 6/58 (10.3%) 7 1/52 (1.9%) 1
    Psychiatric disorders
    Adjustment disorder with depressed mood 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Anxiety 2/6 (33.3%) 2 0/2 (0%) 0 4/58 (6.9%) 5 3/52 (5.8%) 3
    Insomnia 2/6 (33.3%) 2 1/2 (50%) 1 3/58 (5.2%) 3 4/52 (7.7%) 4
    Renal and urinary disorders
    Dysuria 0/6 (0%) 0 0/2 (0%) 0 2/58 (3.4%) 2 3/52 (5.8%) 4
    Pollakiuria 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 3/52 (5.8%) 3
    Urinary incontinence 0/6 (0%) 0 0/2 (0%) 0 1/58 (1.7%) 1 4/52 (7.7%) 4
    Reproductive system and breast disorders
    Vaginal discharge 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 3/52 (5.8%) 3
    Vulvovaginal pruritus 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 2 0/52 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/6 (0%) 0 1/2 (50%) 1 11/58 (19%) 11 12/52 (23.1%) 12
    Dyspnoea 0/6 (0%) 0 0/2 (0%) 0 17/58 (29.3%) 20 9/52 (17.3%) 10
    Dyspnoea exertional 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 3 3/52 (5.8%) 3
    Epistaxis 0/6 (0%) 0 1/2 (50%) 2 5/58 (8.6%) 6 1/52 (1.9%) 1
    Hypoxia 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Nasal congestion 0/6 (0%) 0 1/2 (50%) 1 7/58 (12.1%) 7 4/52 (7.7%) 5
    Oropharyngeal pain 2/6 (33.3%) 2 0/2 (0%) 0 7/58 (12.1%) 7 3/52 (5.8%) 3
    Paranasal sinus discomfort 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Productive cough 1/6 (16.7%) 1 0/2 (0%) 0 1/58 (1.7%) 1 0/52 (0%) 0
    Rhinitis allergic 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 2 0/52 (0%) 0
    Sleep apnoea syndrome 1/6 (16.7%) 1 0/2 (0%) 0 0/58 (0%) 0 0/52 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 0/6 (0%) 0 1/2 (50%) 1 10/58 (17.2%) 10 10/52 (19.2%) 10
    Dry skin 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 3 2/52 (3.8%) 2
    Pruritus 0/6 (0%) 0 0/2 (0%) 0 7/58 (12.1%) 10 5/52 (9.6%) 7
    Pruritus generalised 0/6 (0%) 0 0/2 (0%) 0 3/58 (5.2%) 3 2/52 (3.8%) 2
    Rash 0/6 (0%) 0 0/2 (0%) 0 4/58 (6.9%) 5 3/52 (5.8%) 6
    Social circumstances
    Social problem 0/6 (0%) 0 1/2 (50%) 1 0/58 (0%) 0 0/52 (0%) 0
    Vascular disorders
    Flushing 0/6 (0%) 0 0/2 (0%) 0 0/58 (0%) 0 4/52 (7.7%) 5
    Hypertension 1/6 (16.7%) 1 0/2 (0%) 0 2/58 (3.4%) 3 1/52 (1.9%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-575-5979
    Email Clinicaltrials.gov@lilly.com
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01663857
    Other Study ID Numbers:
    • 12517
    • I1D-MC-JIAE
    First Posted:
    Aug 13, 2012
    Last Update Posted:
    Sep 11, 2019
    Last Verified:
    Aug 1, 2019