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A Study of LY2228820 in Participants With Advanced Cancer

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01393990
Collaborator
(none)
89
Enrollment
2
Locations
1
Arm
63.3
Actual Duration (Months)
44.5
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this study is to determine a safe dose of LY2228820 that may be given to participants with advanced cancer. Part A of this study will consist of dose escalation, and Part B will consist of dose confirmation.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
89 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study of an Oral p38 MAPK Inhibitor in Patients With Advanced Cancer
Actual Study Start Date :
Sep 4, 2008
Actual Primary Completion Date :
Feb 1, 2013
Actual Study Completion Date :
Dec 14, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: LY2228820

The study had 4 parts, dose-escalation (Part A), 2 dose-confirmation (Parts B and C), and a tumor-specific expansion for metastatic breast cancer (Part D). Part A: Participants received escalating doses of 10, 20, 40, 65, 90, 120, 160, 200, 300, 420 and 560 milligrams (mg) of LY2228820 every 12 hours on Days 1 through 14 of a 28-day cycle. Part B: Participants received 420 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Participants received midazolam orally 2 days before the first dose and again after the morning dose of study drug on Day 8 during the first cycle of treatment. Part C: Participants received 300 mg of LY2228820 every 12 hours Days 1 through 14 of a 28-day cycle. Part D: Participants received 200 mg and 300 mg of LY2228820 in combination with tamoxifen.

Drug: LY2228820
Administered orally
Other Names:
  • p38 MAP kinase

    • Drug: Midazolam

    Drug: Tamoxifen

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Clinically Significant Effects (Physical Assessments and Safety Lab Tests) [Baseline to study completion (Up to 41 months)]

      Data presented are the number of participants who experienced at least one treatment emergent adverse event (TEAE). A TEAE is defined as an event that first occurred or worsened after the administration of at least 1 dose of study drug, regardless of causality. A summary of serious AEs (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

    Secondary Outcome Measures

    1. Recommended Dose for Phase 2 Studies [Baseline to study completion (Up to 41 months)]

      Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which was determined by Dose-limiting toxicity (DLT). For the purpose of this study, the MTD was defined as the highest dose level at which no more than 33% of participants experience a DLT during Cycle 1.

    2. Percentage of Participants With Best Overall Response [Complete Response (CR)+Partial Response (PR)+Stable Disease (SD)] [Baseline to study completion (Up to 41 months)]

      Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker level in non-target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions. PD was defined as having at least a 20% increase in the sum of the LD of target lesion and appearance of ≥1 new lesion and/or unequivocal progression of existing nontarget lesions. SD was defined as small changes that did not meet the above criteria taking as reference the smallest sum LD since treatment started.

    3. PK: Area Under the Concentration-Time Curve From Time Zero to 8 Hours (AUC0-8) of LY2228820 [Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose]

    4. PK: Maximum Plasma Concentration (Cmax) of LY2228820 [Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose]

    5. Pharmacodynamics (PD): Number of Participants With Greater Than 50% Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) Activity on Day 1 [Cycle 1 Day 1: predose, 1, 2, 4, and 6 h postdose]

      The effect of LY2228820 on PD biomarker was measured as MAPK-activated protein kinase -2 (MAPKAP-K2) level which is regulated by p38 MAPK activity. Inhibition of p38 MAPK activity will result in lower levels of MAPKAPK-2.

    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 cancer (including lymphoma) that is advanced or metastatic disease for which no therapy of higher priority (approved therapies or therapies with published substantial evidence of effectiveness) is available, or for whom no standard therapy exists

    • Have the presence of measurable or nonmeasurable disease as defined by Modified Response Evaluation Criteria in Solid Tumors (mRECIST)

    • 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, or other investigational therapy for at least 14 days (42 days for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy

    • 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 ≥ 12 weeks

    • Are able to swallow capsules and/or tablets

    Exclusion Criteria:

    • Have received treatment within 14 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication

    • Have a history of major surgical resection involving the stomach or small bowel, or have serious preexisting medical conditions (based on judgment of the investigator)

    • Have symptomatic central nervous system malignancy or metastasis (screening is not required)

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

    • Have an active hematologic malignancy other than lymphoma

    • Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). Screening at baseline will not be required for enrollment

    • Concurrent administration of any immunosuppressive therapy

    • Females who are pregnant or lactating

    • Have received, within 7 days of the initial dose of study drug, either grapefruit juice or treatment with a drug that is a known inhibitor or inducer of Cytochrome P450 Enzyme 3A4 (CYP3A4). In addition, participants should not receive grapefruit juice or treatment with a CYP3A4 inhibitor or inducer during the study

    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. Rochester Minnesota 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 (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01393990
    Other Study ID Numbers:
    • 12284
    • I1D-MC-JIAD
    First Posted:
    Jul 14, 2011
    Last Update Posted:
    Mar 24, 2020
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Neoplasms
    Tamoxifen
    Midazolam

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail The study had 4 parts, dose-escalation (Part A), 2 dose-confirmation (Parts B and C), and a tumor-specific expansion for metastatic breast cancer (Part D). Completers for Parts A and D were defined as any participant who completed Cycle 2 or had a dose-limiting toxicology (DLT) in Cycle 1 and did not enter Cycle 2.
    Arm/Group Title Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg Bridge LY2228820 Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A: 300 mg LY2228820 Tablets Part A: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part B: 420 mg LY2228820 Tablets Part C: 300 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    Arm/Group Description 10 milligrams (mg) LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. In Cycle 1, participants received a single dose of 160 mg LY2228820 comprising tablets (Day -14) or capsules (Day -7). In Cycle 2 and beyond, participants received capsules or tablets of 160 mg LY2228820 twice a day on Days 1 through 14 of a 28 day cycle. 160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.
    Period Title: Overall Study
    STARTED 4 3 3 3 5 3 3 7 6 3 3 3 3 5 18 8 3 6
    Received at Least 1 Dose of Study Drug 4 3 3 3 5 3 3 7 6 3 3 3 3 5 18 8 3 6
    COMPLETED 3 3 3 2 3 2 2 6 3 2 3 3 3 3 9 5 3 6
    NOT COMPLETED 1 0 0 1 2 1 1 1 3 1 0 0 0 2 9 3 0 0

    Baseline Characteristics

    Arm/Group Title Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg Bridge LY2228820 Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A: 300 mg LY2228820 Tablets Part A: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part B: 420 mg LY2228820 Tablets Part C: 300 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets Total
    Arm/Group Description 10 milligrams (mg) LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. In Cycle 1, participants received a single dose of 160 mg LY2228820 comprising tablets (Day -14) or capsules (Day -7). In Cycle 2 and beyond, participants received capsules or tablets of 160 mg LY2228820 twice a day on Days 1 through 14 of a 28 day cycle. 160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day. Total of all reporting groups
    Overall Participants 4 3 3 3 5 3 3 7 6 3 3 3 3 5 18 8 3 6 89
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    60.5
    (11.82)
    60.9
    (2.09)
    63.8
    (2.63)
    61.3
    (9.66)
    64.5
    (11.13)
    66.0
    (13.58)
    61.5
    (1.98)
    64.9
    (11.90)
    61.5
    (10.80)
    64.4
    (4.54)
    49.6
    (16.79)
    51.1
    (15.50)
    56.2
    (17.60)
    70.6
    (8.33)
    61.1
    (10.42)
    58.3
    (8.49)
    56.4
    (1.15)
    62.5
    (4.64)
    61.3
    (10.13)
    Sex: Female, Male (Count of Participants)
    Female
    2
    50%
    1
    33.3%
    3
    100%
    2
    66.7%
    2
    40%
    1
    33.3%
    0
    0%
    5
    71.4%
    4
    66.7%
    1
    33.3%
    3
    100%
    0
    0%
    2
    66.7%
    1
    20%
    12
    66.7%
    4
    50%
    3
    100%
    6
    100%
    52
    58.4%
    Male
    2
    50%
    2
    66.7%
    0
    0%
    1
    33.3%
    3
    60%
    2
    66.7%
    3
    100%
    2
    28.6%
    2
    33.3%
    2
    66.7%
    0
    0%
    3
    100%
    1
    33.3%
    4
    80%
    6
    33.3%
    4
    50%
    0
    0%
    0
    0%
    37
    41.6%
    Race/Ethnicity, Customized (Count of Participants)
    African
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    3.4%
    Caucasian
    3
    75%
    2
    66.7%
    3
    100%
    3
    100%
    5
    100%
    3
    100%
    3
    100%
    6
    85.7%
    6
    100%
    3
    100%
    2
    66.7%
    3
    100%
    2
    66.7%
    4
    80%
    18
    100%
    8
    100%
    3
    100%
    5
    83.3%
    82
    92.1%
    Hispanic
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    4
    4.5%
    Region of Enrollment (Count of Participants)
    United States
    4
    100%
    3
    100%
    3
    100%
    3
    100%
    5
    100%
    3
    100%
    3
    100%
    7
    100%
    6
    100%
    3
    100%
    3
    100%
    3
    100%
    3
    100%
    5
    100%
    18
    100%
    8
    100%
    3
    100%
    6
    100%
    89
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Clinically Significant Effects (Physical Assessments and Safety Lab Tests)
    Description Data presented are the number of participants who experienced at least one treatment emergent adverse event (TEAE). A TEAE is defined as an event that first occurred or worsened after the administration of at least 1 dose of study drug, regardless of causality. A summary of serious AEs (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
    Time Frame Baseline to study completion (Up to 41 months)

    Outcome Measure Data

    Analysis Population Description
    Any participant who received at least 1 dose of study drug.
    Arm/Group Title Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg LY2228820 Bridge Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A: 300 mg LY2228820 Tablets Part A: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part B: 420 mg LY2228820 Tablets Part C: 300 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    Arm/Group Description 10 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. In Cycle 1, participants received a single dose of 160 mg LY2228820 comprising tablets (Day -14) or capsules (Day -7). In Cycle 2 and beyond, participants received capsules or tablets of 160 mg LY2228820 twice a day on Days 1 through 14 of a 28 day cycle. 160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.
    Measure Participants 4 3 3 3 5 3 3 7 6 3 3 3 3 5 18 8 3 6
    Count of Participants [Participants]
    1
    25%
    3
    100%
    2
    66.7%
    3
    100%
    1
    20%
    1
    33.3%
    1
    33.3%
    5
    71.4%
    4
    66.7%
    1
    33.3%
    3
    100%
    3
    100%
    3
    100%
    4
    80%
    18
    100%
    7
    87.5%
    3
    100%
    6
    100%
    2. Secondary Outcome
    Title Recommended Dose for Phase 2 Studies
    Description Recommended Phase 2 dose was determined by maximum tolerated dose (MTD), which was determined by Dose-limiting toxicity (DLT). For the purpose of this study, the MTD was defined as the highest dose level at which no more than 33% of participants experience a DLT during Cycle 1.
    Time Frame Baseline to study completion (Up to 41 months)

    Outcome Measure Data

    Analysis Population Description
    Any participant who received at least 1 dose of study drug.
    Arm/Group Title LY2228820
    Arm/Group Description In Part A, participants received 10, 20, 40, 65, 90, 120, 160,or 200 mg LY2228820 in capsule form and 160, 200, 300, 420 or 560 mg LY2228820 in tablet form twice a day for Days 1 through 14 of 28-day cycles. In Part B participants received 420 mg LY2228820 tablets twice a day for Days 1 through 14 along with a single dose of 2 mg midazolam (on Days 1 and 8) in Cycle 1 of 28-day cycles. In Part C participants received 300 mg LY2228820 tablets twice a day on Days 1 through 14 of 28-day cycles. In Part D participants received 200 mg or 300 mg LY2228820 tablets twice a day on Days 1 through 14 of 28-day cycles and 20 mg tamoxifen on Days 1 through 28 of 28-day cycles. Part A bridging component tested the PK of capsule versus tablet formulation of LY2228820 and tablet was administered subsequently to all participants in the study.
    Measure Participants 89
    Number [milligrams (mg)]
    300
    3. Secondary Outcome
    Title Percentage of Participants With Best Overall Response [Complete Response (CR)+Partial Response (PR)+Stable Disease (SD)]
    Description Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker level in non-target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions. PD was defined as having at least a 20% increase in the sum of the LD of target lesion and appearance of ≥1 new lesion and/or unequivocal progression of existing nontarget lesions. SD was defined as small changes that did not meet the above criteria taking as reference the smallest sum LD since treatment started.
    Time Frame Baseline to study completion (Up to 41 months)

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug.
    Arm/Group Title Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg Bridge LY2228820 Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A: 300 mg LY2228820 Tablets Part A: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part B: 420 mg LY2228820 Tablets Part C: 300 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    Arm/Group Description 10 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. In Cycle 1, participants received a single dose of 160 mg LY2228820 comprising tablets (Day -14) or capsules (Day -7). In Cycle 2 and beyond, participants received capsules or tablets of 160 mg LY2228820 twice a day on Days 1 through 14 of a 28 day cycle. 160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.
    Measure Participants 4 3 3 3 5 3 3 7 6 3 3 3 3 5 18 8 3 6
    Number [percentage of participants]
    25.0
    625%
    33.3
    1110%
    33.3
    1110%
    33.3
    1110%
    40.0
    800%
    33.3
    1110%
    66.7
    2223.3%
    28.6
    408.6%
    16.7
    278.3%
    33.3
    1110%
    33.3
    1110%
    0.0
    0%
    33.3
    1110%
    0.0
    0%
    16.7
    92.8%
    0.0
    0%
    0.0
    0%
    16.7
    278.3%
    4. Secondary Outcome
    Title PK: Area Under the Concentration-Time Curve From Time Zero to 8 Hours (AUC0-8) of LY2228820
    Description
    Time Frame Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug and had evaluable PK data. Participants in 300 mg and 420 mg are combined to measure PK outcome; as dose, formulations and population are same.
    Arm/Group Title Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A and Part C: 300 mg LY2228820 Tablets Part A and Part B: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    Arm/Group Description 10 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. Part A: 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. Part C: 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Part A: 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. Part B: 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1. 560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.
    Measure Participants 4 3 3 3 5 3 3 7 3 3 11 21 5 3 6
    Cycle 1 Day 1
    55.6
    (36)
    257
    (26)
    375
    (79)
    445
    (83)
    707
    (45)
    1310
    (33)
    2120
    (39)
    2550
    (55)
    1750
    (20)
    1720
    (70)
    3460
    (51)
    5780
    (57)
    8880
    (37)
    2360
    (35)
    4500
    (36)
    Cycle 1 Day 14
    151
    (83)
    372
    (28)
    1070
    (130)
    1300
    (13)
    827
    (61)
    1960
    (50)
    6000
    (29)
    6220
    (42)
    2810
    (22)
    NA
    (NA)
    6620
    (85)
    10200
    (55)
    NA
    (NA)
    3810
    (116)
    6910
    (55)
    5. Secondary Outcome
    Title PK: Maximum Plasma Concentration (Cmax) of LY2228820
    Description
    Time Frame Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study treatment and had evaluable PK data. Participants in 300 mg and 420 mg are combined to measure PK outcome; as dose, formulations and population are same.
    Arm/Group Title Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A and Part C: 300 mg LY2228820 Tablets Part A and Part B: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    Arm/Group Description 10 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. Part A: 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. Part C: 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Part A: 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. Part B: 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1. 560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.
    Measure Participants 4 3 3 3 5 3 3 7 3 3 11 21 5 3 6
    Cycle 1 Day 1
    14.7
    (75)
    90.1
    (75)
    144
    (83)
    135
    (87)
    202
    (62)
    405
    (68)
    606
    (53)
    673
    (55)
    454
    (18)
    636
    (78)
    1020
    (58)
    1700
    (71)
    2360
    (28)
    718
    (27)
    1810
    (42)
    Cycle 1 Day 14
    28.4
    (63)
    81.4
    (63)
    252
    (144)
    415
    (14)
    208
    (74)
    530
    (38)
    1930
    (64)
    1330
    (56)
    574
    (11)
    963
    (82)
    1400
    (81)
    2230
    (53)
    NA
    (NA)
    1030
    (185)
    1700
    (52)
    6. Secondary Outcome
    Title Pharmacodynamics (PD): Number of Participants With Greater Than 50% Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) Activity on Day 1
    Description The effect of LY2228820 on PD biomarker was measured as MAPK-activated protein kinase -2 (MAPKAP-K2) level which is regulated by p38 MAPK activity. Inhibition of p38 MAPK activity will result in lower levels of MAPKAPK-2.
    Time Frame Cycle 1 Day 1: predose, 1, 2, 4, and 6 h postdose

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug and had evaluable PD data. At the dose confirmation of 300 mg, the pMAPKAP-K2 inhibition reached above 50% on Day 1 as maximum inhibition.
    Arm/Group Title Part A, C and D: LY2228820 300 mg Tablets
    Arm/Group Description Part A: 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. Part C: 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Part D: 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.
    Measure Participants 14
    Count of Participants [Participants]
    14
    350%

    Adverse Events

    Time Frame Up to 41 Months
    Adverse Event Reporting Description All participants who received at least 1 dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
    Arm/Group Title Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg LY2228820 Bridge Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A: 300 mg LY2228820 Tablets Part A: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part B: 420 mg LY2228820 Tablets Part C: 300 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    Arm/Group Description 10 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 20 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 40 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 65 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 90 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 120 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 160 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally in capsule form every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. In Cycle 1, participants received a single dose of 160 mg LY2228820 comprising tablets (Day -14) or capsules (Day -7). In Cycle 2 and beyond, participants received capsules or tablets of 160 mg LY2228820 twice a day on Days 1 through 14 of a 28 day cycle. 160 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 560 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants could continue treatment if there was benefit and they did not meet the discontinuation criteria. 420 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg oral midazolam 2 days before the first dose of LY2228820 and again after the morning dose of study drug on Day 8 of Cycle 1. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. 200 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day. 300 mg LY2228820 was administered orally as tablets every 12 hours on Days 1 through 14 of a 28-day cycle for at least 2 cycles if no discontinuation criteria were met. Participants received 20 mg tamoxifen once a day.
    All Cause Mortality
    Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg LY2228820 Bridge Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A: 300 mg LY2228820 Tablets Part A: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part B: 420 mg LY2228820 Tablets Part C: 300 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    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 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/5 (20%) 0/3 (0%) 0/3 (0%) 0/7 (0%) 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/5 (20%) 1/18 (5.6%) 0/8 (0%) 0/3 (0%) 0/6 (0%)
    Serious Adverse Events
    Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg LY2228820 Bridge Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A: 300 mg LY2228820 Tablets Part A: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part B: 420 mg LY2228820 Tablets Part C: 300 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    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 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/4 (50%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 3/5 (60%) 0/3 (0%) 2/3 (66.7%) 2/7 (28.6%) 2/6 (33.3%) 3/3 (100%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 3/5 (60%) 7/18 (38.9%) 4/8 (50%) 0/3 (0%) 0/6 (0%)
    Blood and lymphatic system disorders
    Anaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 2 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Cyanosis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Tachycardia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Gastrointestinal disorders
    Constipation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Duodenal ulcer 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Small intestinal haemorrhage 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 2 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Small intestinal obstruction 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    General disorders
    Fatigue 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pyrexia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hepatobiliary disorders
    Hepatic failure 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Immune system disorders
    Hypersensitivity 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Infections and infestations
    Bronchitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Cellulitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Endocarditis enterococcal 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Escherichia bacteraemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Herpes simplex 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Lobar pneumonia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pneumonia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Urinary tract infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Injury, poisoning and procedural complications
    Exposure during pregnancy 0/2 (0%) 0 0/1 (0%) 0 0/3 (0%) 0 0/2 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/0 (NaN) 0 0/5 (0%) 0 0/4 (0%) 0 0/1 (0%) 0 1/3 (33.3%) 1 0/0 (NaN) 0 0/2 (0%) 0 0/1 (0%) 0 0/12 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Fall 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 2/8 (25%) 2 0/3 (0%) 0 0/6 (0%) 0
    Investigations
    Bilirubin conjugated increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Blood bilirubin increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Blood creatine phosphokinase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Blood creatinine increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Hypercalcaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hyperuricaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hypoglycaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hyponatraemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hypovolaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Flank pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant ascites 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Nervous system disorders
    Ataxia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Cerebral haemorrhage 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Convulsion 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Dizziness 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 0/2 (0%) 0 0/1 (0%) 0 0/3 (0%) 0 0/2 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/0 (NaN) 0 0/5 (0%) 0 0/4 (0%) 0 0/1 (0%) 0 1/3 (33.3%) 1 0/0 (NaN) 0 0/2 (0%) 0 0/1 (0%) 0 0/12 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Psychiatric disorders
    Confusional state 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hallucination 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Mental status changes 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Renal and urinary disorders
    Hydronephrosis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Renal failure 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Renal failure acute 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Renal failure chronic 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/5 (40%) 2 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hypercapnia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hypoxia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pleural effusion 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pulmonary embolism 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Pulmonary oedema 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Respiratory arrest 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Tachypnoea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 2/18 (11.1%) 2 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Other (Not Including Serious) Adverse Events
    Part A: 10 mg LY2228820 Capsules Part A: 20 mg LY2228820 Capsules Part A: 40 mg LY2228820 Capsules Part A: 65 mg LY2228820 Capsules Part A: 90 mg LY2228820 Capsules Part A: 120 mg LY2228820 Capsules Part A: 160 mg LY2228820 Capsules Part A: 200 mg LY2228820 Capsules Part A: 160 mg LY2228820 Bridge Part A: 160 mg LY2228820 Tablets Part A: 200 mg LY2228820 Tablets Part A: 300 mg LY2228820 Tablets Part A: 420 mg LY2228820 Tablets Part A: 560 mg LY2228820 Tablets Part B: 420 mg LY2228820 Tablets Part C: 300 mg LY2228820 Tablets Part D: 200 mg LY2228820 Tablets Part D: 300 mg LY2228820 Tablets
    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 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 Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/4 (75%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 2/5 (40%) 3/3 (100%) 2/3 (66.7%) 6/7 (85.7%) 6/6 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 5/5 (100%) 18/18 (100%) 7/8 (87.5%) 3/3 (100%) 6/6 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 3/6 (50%) 3 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 2/18 (11.1%) 2 1/8 (12.5%) 1 0/3 (0%) 0 3/6 (50%) 4
    Leukopenia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Lymphopenia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Neutropenia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Neutrophilia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Thrombocytopenia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 2 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Thrombocytosis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Palpitations 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pulmonary valve incompetence 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Tachycardia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Ear and labyrinth disorders
    Ear discomfort 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Ear pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Eye disorders
    Blepharitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Dry eye 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Eye irritation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Eye pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Eye swelling 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Foreign body sensation in eyes 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Lacrimation increased 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Periorbital oedema 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Vision blurred 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Gastrointestinal disorders
    Abdominal discomfort 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Abdominal distension 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/5 (0%) 0 3/18 (16.7%) 3 2/8 (25%) 2 0/3 (0%) 0 0/6 (0%) 0
    Abdominal pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Abdominal pain upper 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Abdominal tenderness 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Aphthous stomatitis 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Ascites 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Constipation 1/4 (25%) 1 1/3 (33.3%) 1 2/3 (66.7%) 2 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/7 (28.6%) 4 1/6 (16.7%) 1 2/3 (66.7%) 2 2/3 (66.7%) 2 2/3 (66.7%) 2 1/3 (33.3%) 1 1/5 (20%) 1 6/18 (33.3%) 6 5/8 (62.5%) 5 1/3 (33.3%) 1 3/6 (50%) 4
    Diarrhoea 0/4 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 2/3 (66.7%) 2 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 1/6 (16.7%) 1 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 1/5 (20%) 1 3/18 (16.7%) 4 0/8 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 3
    Diarrhoea haemorrhagic 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Dry mouth 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 2 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Dyspepsia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 2/18 (11.1%) 2 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Dysphagia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Eructation 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Faecal incontinence 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Flatulence 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Gastrooesophageal reflux disease 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hypoaesthesia oral 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Melaena 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Nausea 0/4 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 2 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 1/7 (14.3%) 1 4/6 (66.7%) 4 0/3 (0%) 0 2/3 (66.7%) 3 1/3 (33.3%) 1 1/3 (33.3%) 3 1/5 (20%) 1 6/18 (33.3%) 6 2/8 (25%) 2 0/3 (0%) 0 3/6 (50%) 6
    Odynophagia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Rectal haemorrhage 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Salivary gland disorder 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Small intestinal obstruction 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Stomatitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/5 (20%) 1 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2
    Vomiting 0/4 (0%) 0 3/3 (100%) 4 1/3 (33.3%) 1 1/3 (33.3%) 1 0/5 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/7 (0%) 0 3/6 (50%) 3 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 5/18 (27.8%) 5 1/8 (12.5%) 1 0/3 (0%) 0 2/6 (33.3%) 6
    General disorders
    Asthenia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Chest discomfort 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Chest pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Chills 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 1/3 (33.3%) 2 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 1/6 (16.7%) 3
    Fatigue 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/5 (20%) 1 3/3 (100%) 3 1/3 (33.3%) 1 3/7 (42.9%) 3 4/6 (66.7%) 4 1/3 (33.3%) 1 3/3 (100%) 3 1/3 (33.3%) 1 0/3 (0%) 0 1/5 (20%) 1 6/18 (33.3%) 6 3/8 (37.5%) 3 1/3 (33.3%) 1 5/6 (83.3%) 6
    Feeling jittery 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Mucosal inflammation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1
    Non-cardiac chest pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Oedema 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Oedema peripheral 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 1/8 (12.5%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Pyrexia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/5 (40%) 2 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Thirst 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Immune system disorders
    Seasonal allergy 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Infections and infestations
    Cellulitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Cystitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Diverticulitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Ear infection 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Fungal infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Gastroenteritis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Groin abscess 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Laryngitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Oral candidiasis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Oral herpes 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Respiratory tract infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Sinusitis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Tinea infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Tooth infection 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Upper respiratory tract infection 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Injury, poisoning and procedural complications
    Eye contusion 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Humerus fracture 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Ligament sprain 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Investigations
    Activated partial thromboplastin time prolonged 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Alanine aminotransferase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 2/18 (11.1%) 2 1/8 (12.5%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Aspartate aminotransferase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 1/18 (5.6%) 1 2/8 (25%) 2 0/3 (0%) 0 2/6 (33.3%) 2
    Blood alkaline phosphatase increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Blood creatine phosphokinase decreased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Blood creatine phosphokinase increased 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 5
    Blood creatinine increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 2/6 (33.3%) 2 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/5 (40%) 2 1/18 (5.6%) 1 1/8 (12.5%) 2 0/3 (0%) 0 0/6 (0%) 0
    Blood urea increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Blood uric acid increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Breath sounds abnormal 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Cardiac murmur 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Electrocardiogram t wave abnormal 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Heart rate irregular 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    International normalised ratio increased 1/4 (25%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Lymphocyte count increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Neutrophil count increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Prothrombin time prolonged 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Weight decreased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    White blood cell count increased 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 3
    Metabolism and nutrition disorders
    Decreased appetite 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 2/7 (28.6%) 2 3/6 (50%) 3 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 2/5 (40%) 2 8/18 (44.4%) 8 1/8 (12.5%) 1 0/3 (0%) 0 1/6 (16.7%) 3
    Dehydration 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 2/3 (66.7%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 2/8 (25%) 2 0/3 (0%) 0 1/6 (16.7%) 1
    Hypercalcaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Hypercholesterolaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hyperglycaemia 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Hyperkalaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2
    Hypernatraemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Hypoalbuminaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 3/18 (16.7%) 4 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hypocalcaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 3 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Hypokalaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 2/18 (11.1%) 2 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Hypomagnesaemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hyponatraemia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 2/18 (11.1%) 2 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 4
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2
    Back pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 1/18 (5.6%) 1 0/8 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Flank pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Joint swelling 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Limb discomfort 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Muscle spasms 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Muscular weakness 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Musculoskeletal chest pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Musculoskeletal discomfort 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Musculoskeletal pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Musculoskeletal stiffness 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Myalgia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Neck pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Osteoarthritis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Pain in extremity 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 2/18 (11.1%) 2 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pain in jaw 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Trismus 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour associated fever 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Tumour pain 0/4 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 2/3 (66.7%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 3/8 (37.5%) 3 0/3 (0%) 0 0/6 (0%) 0
    Nervous system disorders
    Ataxia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Coordination abnormal 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Cranial nerve disorder 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Dizziness 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/7 (14.3%) 1 1/6 (16.7%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 4 1/5 (20%) 1 7/18 (38.9%) 8 2/8 (25%) 2 1/3 (33.3%) 1 1/6 (16.7%) 1
    Dysgeusia 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 2/3 (66.7%) 2 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Headache 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 3
    Neuralgia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Neuropathy peripheral 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Paraesthesia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Peripheral sensory neuropathy 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Radicular pain 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Sinus headache 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Somnolence 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Spinal cord compression 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Tremor 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 2/3 (66.7%) 3 2/5 (40%) 2 4/18 (22.2%) 4 1/8 (12.5%) 1 0/3 (0%) 0 1/6 (16.7%) 1
    Psychiatric disorders
    Anxiety 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Confusional state 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/5 (40%) 2 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Depression 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Disinhibition 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Disorientation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Insomnia 0/4 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Renal and urinary disorders
    Dysuria 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Haematuria 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Pollakiuria 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Renal failure chronic 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Urinary incontinence 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Urinary retention 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Reproductive system and breast disorders
    Genital rash 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Perineal cyst 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Vulvovaginal pruritus 0/2 (0%) 0 0/1 (0%) 0 0/3 (0%) 0 0/2 (0%) 0 0/2 (0%) 0 0/1 (0%) 0 0/0 (NaN) 0 0/5 (0%) 0 0/4 (0%) 0 0/1 (0%) 0 0/3 (0%) 0 0/0 (NaN) 0 1/2 (50%) 1 0/1 (0%) 0 0/12 (0%) 0 0/4 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 3/18 (16.7%) 3 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Dyspnoea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 5/18 (27.8%) 5 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Epistaxis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Haemoptysis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/5 (40%) 2 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hiccups 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/5 (20%) 1 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Nasal congestion 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Nasal dryness 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Oropharyngeal pain 1/4 (25%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pleural effusion 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Respiratory disorder 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Respiratory tract congestion 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Rhinitis allergic 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0
    Rhinorrhoea 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Wheezing 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Skin and subcutaneous tissue disorders
    Acne 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Alopecia 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Dermal cyst 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Dermatitis acneiform 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Dry skin 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 3/18 (16.7%) 3 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Ecchymosis 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Erythema 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Erythema multiforme 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hyperhidrosis 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Ingrowing nail 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Nail disorder 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Pruritus 1/4 (25%) 1 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/5 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 1/3 (33.3%) 1 1/3 (33.3%) 1 1/5 (20%) 1 4/18 (22.2%) 4 0/8 (0%) 0 1/3 (33.3%) 1 3/6 (50%) 4
    Purpura 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Rash 0/4 (0%) 0 1/3 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 1/5 (20%) 1 0/3 (0%) 0 0/3 (0%) 0 1/7 (14.3%) 1 1/6 (16.7%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 4/5 (80%) 5 7/18 (38.9%) 7 2/8 (25%) 2 1/3 (33.3%) 1 4/6 (66.7%) 8
    Rash erythematous 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Rash macular 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 2/18 (11.1%) 3 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Rash maculo-papular 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 1/8 (12.5%) 1 0/3 (0%) 0 0/6 (0%) 0
    Rash pruritic 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 1/6 (16.7%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Skin exfoliation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Skin fissures 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 1/18 (5.6%) 1 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Skin irritation 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Swelling face 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1
    Vascular disorders
    Hot flush 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hypertension 0/4 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 0/6 (0%) 0
    Hypotension 0/4 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/7 (0%) 0 0/6 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/5 (0%) 0 0/18 (0%) 0 0/8 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 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 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01393990
    Other Study ID Numbers:
    • 12284
    • I1D-MC-JIAD
    First Posted:
    Jul 14, 2011
    Last Update Posted:
    Mar 24, 2020
    Last Verified:
    Mar 1, 2020