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    Clinical Trial Results:
    A Phase 1b/2 Double-Blind Randomized Trial of the Hedgehog/SMO Antagonist LY2940680 in Combination with Carboplatin and Etoposide Followed by LY2940680 versus Carboplatin and Etoposide Plus Placebo Followed by Placebo in Patients with Extensive-Stage Small Cell Lung Cancer

    Summary
    EudraCT number
    		 2012-003174-83
    Trial protocol
    		 GB   BE  
    Global end of trial date
    19 Feb 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Nov 2018
    First version publication date
    01 Nov 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I4J-MC-HHBE
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01722292
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Trial Number: 14631
    Sponsors
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly, 1 877‐285‐4559,
    Sponsor organisation name
    Eli Lilly and Company
    Sponsor organisation address
    Lilly Corporate Center, Indianapolis, IN, United States, 46285
    Public contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐CTLilly,
    Scientific contact
    Available Mon ‐ Fri 9 AM ‐ 5 PM EST, Eli Lilly and Company, 1 877‐285‐4559,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Feb 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Feb 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of this study is to find a recommended dose of LY2940680 that can be safely given in combination with etoposide and carboplatin followed by LY2940680 alone in participants with extensive-disease small cell lung cancer. The study will also compare progression-free survival in participants who are administered etoposide, carboplatin and LY2940680 followed by LY2940680 alone versus etoposide, carboplatin, and placebo followed by placebo alone.
    Protection of trial subjects
    This study was conducted in accordance with International Conference on Harmonization (ICH) Good Clinical Practice, and the principles of the Declaration of Helsinki, in addition to following the laws and regulations of the country or countries in which a study is conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Jan 2013
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 3 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 20
    Country: Number of subjects enrolled
    United Kingdom: 6
    Worldwide total number of subjects
    26
    EEA total number of subjects
    6
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    15
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped. Phase 1b study completer was defined as completion of the dose-limiting toxicity (DLT) period (1 cycle- 21 days cycle for LY2940680 in combination with carboplatin and etoposide.

    Pre-assignment
    Screening details
    		 No Text Entered

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase 1b: 100 mg LY2940680 + C + E
    Arm description
    		 100 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LY2940680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    100 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles.

    Investigational medicinal product name
    Etoposide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

    Arm title
    		 Phase 1b: 200 mg LY2940680 + C + E
    Arm description
    		 200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LY2940680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg LY2940680 administered orally once daily (QD) for 6 cycles.

    Investigational medicinal product name
    Etoposide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance:

    Arm title
    		 Phase 1b: 400 mg LY2940680 + C + E
    Arm description
    		 400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.
    Arm type
    		 Experimental

    Investigational medicinal product name
    LY2940680
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    400 mg LY2940680 administered orally once daily (QD) for 6 cycles.

    Investigational medicinal product name
    Etoposide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle.

    Investigational medicinal product name
    Carboplatin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

    Number of subjects in period 1
    		Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E
    Started
    6
    6
    14
    Received at Least One Dose of Study
    6
    6
    14
    Completed
    6
    6
    14

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Phase 1b: 100 mg LY2940680 + C + E
    Reporting group description
    		 100 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

    Reporting group title
    Phase 1b: 200 mg LY2940680 + C + E
    Reporting group description
    		 200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

    Reporting group title
    Phase 1b: 400 mg LY2940680 + C + E
    Reporting group description
    		 400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

    Reporting group values
    		 Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E Total
    Number of subjects
    		 6 6 14 26
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.3 ± 9.35 64.8 ± 11.96 60.2 ± 12.19 -
    Gender categorical
    Units: Subjects
        Female
    		 3 3 7 13
        Male
    		 3 3 7 13
    Race
    Units: Subjects
        Black or African American
    		 0 2 1 3
        White
    		 6 3 13 22
        Unknown or Not Reported
    		 0 1 0 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 1 0 1
        Not Hispanic or Latino
    		 6 5 14 25
        Unknown or Not Reported
    		 0 0 0 0
    Region of Enrollment
    Units: Subjects
        United States
    		 5 5 10 20
        United Kingdom
    		 1 1 4 6

    End points

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    End points reporting groups
    Reporting group title
    Phase 1b: 100 mg LY2940680 + C + E
    Reporting group description
    		 100 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

    Reporting group title
    Phase 1b: 200 mg LY2940680 + C + E
    Reporting group description
    		 200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

    Reporting group title
    Phase 1b: 400 mg LY2940680 + C + E
    Reporting group description
    		 400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve (AUC) 5 milligrams*minute*milliliters (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Maintenance: Single-agent LY2940680 administered orally QD at the same dose as induction at Cycles 7+ (21 day cycles). Participants receiving benefit may continue until disease progression, unacceptable toxicity, or discontinuation.

    Subject analysis set title
    Phase 1b
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Cohort 1: 100 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve [AUC] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Cohort 2: 200 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve [AUC] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle. Cohort 3: 400 milligrams (mg) LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve [AUC] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

    Subject analysis set title
    Phase 2: 400 mg LY2940680 + C+ E
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    400 mg LY2940680 administered orally QD cycles 1-6 (21 day cycle). (AUC) 5 carboplatin (C) administered by IV infusion on day 1 each cycle. 100 mg/m² etoposide (E) administered by IV infusion on days 1, 2, 3 of each cycle, followed by a single agent of LY2940680. 26 participants completed Phase 1 and zero participants analyzed for phase 2. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

    Subject analysis set title
    Phase 2: Placebo + C + E
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Placebo administered orally QD for 6 cycles. (AUC) 5 carboplatin administered by IV infusion on day 1 of each cycle. 100 mg/m² etoposide administered by IV infusion on days 1, 2, 3 of each cycle. 26 participants completed Phase 1 and zero participants analyzed for phase 2. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.

    Primary: Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD)

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    End point title
    		 Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD) [1]
    End point description
    MTD was defined as the highest tested dose that has<33% probability of causing a dose-limiting toxicity(DLT).DLT was defined as an AE during Cycle 1 that is possibly related to the study drug and fulfills any one of the following criterion using the National Cancer Institute(NCI) Common Terminology Criteria for Adverse Events(CTCAE),version 4.0:Grade 3 non-hematological toxicity except nausea, vomiting, constipation, diarrhea, fatigue, or anorexia that is manageable with appropriate care,transient(i.e., ≤5 days) Grade 3 elevations of alanine aminotransferase(ALT) and/or aspartate aminotransferase(AST), without evidence of other hepatic injury, in the setting of preexisting hepatic metastasis,≥Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia of any duration,CTCAE Grade 4 hematological toxicity of >5 days duration and any febrile neutropenia or any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose-limiting.
    End point type
    Primary
    End point timeframe
    Timeframe: Baseline to Completion of the Phase 1b (Up To 12 Months) Analysis Population Description (APD) - All participants who received at least one dose of study drug and were enrolled in Phase1b of the study.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No arm comparison analyses were planned or conducted.
    End point values
    		 Phase 1b
    Number of subjects analysed
    26
    Units: milligrams (mg)
        number (not applicable)
    400
    No statistical analyses for this end point

    Primary: Phase 2: Progression-Free Survival

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    End point title
    		 Phase 2: Progression-Free Survival [2]
    End point description
    Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
    End point type
    Primary
    End point timeframe
    Randomization to Measured Progressive Disease or Death of Any Cause (Estimated as 18 Months)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
    End point values
    		 Phase 2: 400 mg LY2940680 + C+ E Phase 2: Placebo + C + E
    Number of subjects analysed
    0 [3]
    0 [4]
    Units: months
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [3] - 26 participants completed Phase 1b. Phase 2 portion was not initiated.
    [4] - 26 participants completed Phase 1b. Phase 2 portion was not initiated.
    No statistical analyses for this end point

    Secondary: Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556, Carboplatin, and Etoposide at the Recommended Dose

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    End point title
    		 Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556, Carboplatin, and Etoposide at the Recommended Dose
    End point description
    APD: All participants who received at least one dose of study drug and were enrolled in Phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped. 9999=Not Applicable (NA). Carboplatin and Etoposide are given as fixed dose whatever cohort the participants are for the LY2940680 dose. PK analysis results were grouped together in the Phase 1b: 200 mg LY2940680 + C + E arm.
    End point type
    Secondary
    End point timeframe
    Cycle(C)1 Day(D)1:Predose(Pr),0.5 hour(h),1h,2h,4h,6h,8h;C1 D2: Pr,0.5h;C1 D3,Pr,0.5h;C2 D1:Pr,0.5h,1h,2h,4h,6h,8h;C2 D2:Pr,0.5h;C2 D3:Pr,0.5h;C6 D1:Pr;C7 D1: Pr,0.5h,1h,2h,4h,6h,8h;C7 D2: Pr
    End point values
    		 Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E
    Number of subjects analysed
    6
    6
    14
    Units: microgram per milliliter (µg/mL)
    geometric mean (geometric coefficient of variation)
        LY2940680 Cycle 1, Day 1
    0.491 ± 64
    1.01 ± 36
    1.56 ± 35
        LY2940680 Cycle 2, Day 1
    0.578 ± 71
    1.16 ± 66
    3.29 ± 33
        LSN3185556 Cycle 1, Day 1
    0.444 ± 33
    0.737 ± 138
    1.75 ± 47
        LSN3185556 Cycle 2, Day 1
    1.6 ± 35
    2.1 ± 90
    6 ± 59
        Total Carboplatin Cycle 1, Day 1
    9999 ± 9999
    16.7 ± 33
    9999 ± 9999
        Total Carboplatin Cycle 2, Day 1
    9999 ± 9999
    13.1 ± 42
    9999 ± 9999
        Etoposide Cycle 1, Day 1
    9999 ± 9999
    20.9 ± 18
    9999 ± 9999
        Etoposide Cycle 2, Day 1
    9999 ± 9999
    18.4 ± 28
    9999 ± 9999
    No statistical analyses for this end point

    Secondary: Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680, LSN3185556 and Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose

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    End point title
    		 Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680, LSN3185556 and Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose
    End point description
    APD: Carboplatin and Etoposide are given as fixed dose whatever cohort the participants are for the LY2940680 dose. PK analysis results were grouped together in the Phase 1b: 200 mg LY2940680 + C + E arm. 9999=Not Applicable (NA). Carboplatin and Etoposide are given as fixed dose whatever cohort the participants are for the LY2940680 dose. PK analysis results were grouped together in the Phase 1b: 200 mg LY2940680 + C + E arm.
    End point type
    Secondary
    End point timeframe
    C1 D1:Pr,0.5 h,1h,2h,4h,6h,8h;C1 D2: Pr,0.5h;C1 D3:Pr,0.5h;C2 D1:Pr,0.5h,1h,2h,4h,6h,8h;C2 D2:Pr,0.5h;C2 D3:Pr,0.5h;C6 D1:Pr;C7 D1: Pr,0.5h,1h,2h,4h,6h,8h;C7 D2: Pr
    End point values
    		 Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E
    Number of subjects analysed
    6
    6
    14
    Units: Hour*microgram per milliliter (h.µg/mL)
    geometric mean (geometric coefficient of variation)
        LY2940680 Cycle 1, Day 1
    6.34 ± 57
    8.96 ± 39
    15.9 ± 27
        LY2940680 Cycle 2, Day 1
    7.86 ± 67
    15.5 ± 64
    37.6 ± 43
        LSN3185556 Cycle 1, Day 1
    7.23 ± 49
    16.2 ± 67
    26 ± 37
        LSN3185556 Cycle 2, Day 1
    22.7 ± 58
    31.1 ± 111
    92.5 ± 72
        Total Carboplatin Cycle 1, Day 1
    9999 ± 9999
    37.2 ± 23
    9999 ± 9999
        Total Carboplatin Cycle 2, Day 1
    9999 ± 9999
    32.0 ± 25
    9999 ± 9999
        Etoposide Cycle 1, Day 1
    9999 ± 9999
    104 ± 22
    9999 ± 9999
        Etoposide Cycle 2, Day 1
    9999 ± 9999
    96.1 ± 20
    9999 ± 9999
    No statistical analyses for this end point

    Secondary: Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])

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    End point title
    		 Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
    End point description
    ORR was defined as the percentage of all randomized participants with the best overall response of PR or CR using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. APD: All participants who received at least one dose of drug.
    End point type
    Secondary
    End point timeframe
    Baseline to Study Completion Up to 39 Months
    End point values
    		 Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E
    Number of subjects analysed
    6
    6
    14
    Units: Percentage of participnats
        arithmetic mean (confidence interval 90%)
    50 (16.4 to 83.6)
    50 (16.4 to 83.6)
    57.1 (35.4 to 78.9)
    No statistical analyses for this end point

    Secondary: Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells

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    End point title
    		 Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells
    End point description
    The gene expression data (Gli1) was normalized and the level of percentage of Gli1 inhibition post treatment was calculated. APD: All participants who received at least one dose of drug and had samples available.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 7 Day 1
    End point values
    		 Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E
    Number of subjects analysed
    5
    5
    12
    Units: Percentage of Gli 1 Inhibition
        median (inter-quartile range (Q1-Q3))
    94.7 (75.9 to 94.9)
    95.1 (94.5 to 97.2)
    94.8 (90.7 to 97.3)
    No statistical analyses for this end point

    Secondary: Phase 2: Overall Survival

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    End point title
    		 Phase 2: Overall Survival
    End point description
    APD: Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
    End point type
    Secondary
    End point timeframe
    Randomization to Study Completion (Estimated as 38 Months)
    End point values
    		 Phase 2: 400 mg LY2940680 + C+ E Phase 2: Placebo + C + E
    Number of subjects analysed
    0 [5]
    0 [6]
    Units: months
        number (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [5] - 26 participants completed Phase 1b. Phase 2 portion was not initiated.
    [6] - 26 participants completed Phase 1b. Phase 2 portion was not initiated.
    No statistical analyses for this end point

    Secondary: Phase 2: Percent Change in Tumor Size (CTS)

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    End point title
    		 Phase 2: Percent Change in Tumor Size (CTS)
    End point description
    APD: Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
    End point type
    Secondary
    End point timeframe
    Randomization to End of Cycle 2 (Estimated as 24 Months)
    End point values
    		 Phase 2: 400 mg LY2940680 + C+ E Phase 2: Placebo + C + E
    Number of subjects analysed
    0 [7]
    0 [8]
    Units: Percent Tumor change
        number (not applicable)
    Notes
    [7] - 26 participants completed Phase 1b. Phase 2 portion was not initiated.
    [8] - 26 participants completed Phase 1b. Phase 2 portion was not initiated.
    No statistical analyses for this end point

    Secondary: Phase 2: Number of Participants With a Complete or Partial Tumor Response (Overall Response Rate)

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    End point title
    		 Phase 2: Number of Participants With a Complete or Partial Tumor Response (Overall Response Rate)
    End point description
    APD: Zero participants analyzed. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
    End point type
    Secondary
    End point timeframe
    Randomization to Study Completion (Estimated as 38 Months)
    End point values
    		 Phase 2: 400 mg LY2940680 + C+ E Phase 2: Placebo + C + E
    Number of subjects analysed
    0 [9]
    0 [10]
    Units: Participants
        number (not applicable)
    Notes
    [9] - 26 participants completed Phase 1b. Phase 2 portion was not initiated.
    [10] - 26 participants completed Phase 1b. Phase 2 portion was not initiated.
    No statistical analyses for this end point

    Secondary: Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680, LSN3185556, Carboplatin, and Etoposide at the Recommended Dose

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    End point title
    		 Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680, LSN3185556, Carboplatin, and Etoposide at the Recommended Dose
    End point description
    APD: All participants who received at least one dose of study drug and were enrolled in phase 1b study. Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped. 9999=Not Applicable (NA). Carboplatin and Etoposide are given as fixed dose whatever cohort the participants are for the LY2940680 dose. PK analysis results were grouped together in the Phase 1b: 200 mg LY2940680 + C + E arm.
    End point type
    Secondary
    End point timeframe
    C1 D1: Pr,0.5h,1h,2h,4h,6h,8h;C1 D2: Pr,0.5h;C1 D3:Pr,0.5h;C2 D1:Pr,0.5h,1h,2h,4h,6h,8h;C2 D2:Pr,0.5h;C2 D3:Pr,0.5h;C6 D1:Pr;C7 D1: Pr,0.5h,1h,2h,4h,6h,8h;C7 D2: Pr
    End point values
    		 Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E
    Number of subjects analysed
    6
    6
    14
    Units: Hour (h)
    median (full range (min-max))
        LY2940680 Cycle 1, Day 1
    2.05 (1 to 3.98)
    2.01 (1.03 to 2.05)
    1.51 (0.5 to 6)
        LY2940680 Cycle 2, Day 1
    2.96 (0.08 to 5.83)
    4 (1.88 to 4.08)
    1 (0.5 to 6)
        LSN3185556 Cycle 1, Day 2
    6.14 (2 to 24.03)
    5.87 (2.07 to 24.97)
    6 (2.05 to 24)
        LSN3185556 Cycle 2, Day 2
    2.3 (0 to 4)
    4.08 (4 to 23.83)
    2.21 (0.5 to 6)
        Total Carboplatin Cycle 1, Day 1
    9999 (9999 to 9999)
    0.5 (0.42 to 1.08)
    9999 (9999 to 9999)
        Total Carboplatin Cycle 2, Day 1
    9999 (9999 to 9999)
    0.5 (0.42 to 1.05)
    9999 (9999 to 9999)
        Etoposide Cycle 1, Day 1
    9999 (9999 to 9999)
    0.96 (0.48 to 1.5)
    9999 (9999 to 9999)
        Etoposide Cycle 2 ,Day 1
    9999 (9999 to 9999)
    0.99 (0.33 to 1.17)
    9999 (9999 to 9999)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Phase 1b
    Adverse event reporting additional description
    I4J-MC-HHBE
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Phase 1b: 100 mg LY2940680 + C + E
    Reporting group description
    		 100 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve [AUC] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

    Reporting group title
    Phase 1b: 200 mg LY2940680 + C + E
    Reporting group description
    		 200 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve [AUC] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

    Reporting group title
    Phase 1b: 400 mg LY2940680 + C + E
    Reporting group description
    		 400 mg LY2940680 administered orally once daily (QD) for 6 cycles. 100 mg per square meter (mg/m^2) etoposide (E) administered by intravenous (IV) infusion on days 1, 2, 3 of each cycle. Area under the Curve [AUC] 5 (mg•min/mL) carboplatin (C) administered by IV infusion on day 1 each cycle.

    Serious adverse events
    		 Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 6 (50.00%)
    6 / 6 (100.00%)
    8 / 14 (57.14%)
         number of deaths (all causes)
    1
    0
    1
         number of deaths resulting from adverse events
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    malignant neoplasm progression
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    neutrophil count decreased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    hypovolaemic shock
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    acute myocardial infarction
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ventricular extrasystoles
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    cerebral haemorrhage
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    headache
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    nervous system disorder
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    febrile neutropenia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    systemic inflammatory response syndrome
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    diarrhoea
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    enterocolitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pancreatitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    acute respiratory failure
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    pneumonia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    3 / 14 (21.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    dehydration
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase 1b: 100 mg LY2940680 + C + E Phase 1b: 200 mg LY2940680 + C + E Phase 1b: 400 mg LY2940680 + C + E
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    14 / 14 (100.00%)
    Vascular disorders
    hypertension
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    1
    hypotension
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    0
    orthostatic hypotension
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    0
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    1 / 14 (7.14%)
         occurrences all number
    1
    2
    1
    catheter site pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    fatigue
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 6 (66.67%)
    3 / 6 (50.00%)
    11 / 14 (78.57%)
         occurrences all number
    4
    3
    15
    gait disturbance
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    influenza like illness
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    2
    non-cardiac chest pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    2
    oedema peripheral
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    4 / 6 (66.67%)
    2 / 14 (14.29%)
         occurrences all number
    1
    4
    2
    pyrexia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    0
    Immune system disorders
    seasonal allergy
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    1
    Reproductive system and breast disorders
    vaginal haemorrhage
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed [1]
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 7 (14.29%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    2
    dyspnoea
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    3 / 14 (21.43%)
         occurrences all number
    2
    1
    3
    haemoptysis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    hiccups
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    pleural effusion
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    productive cough
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    1
    respiratory failure
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    agitation
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    anxiety
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    1
    depression
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 14 (0.00%)
         occurrences all number
    0
    2
    0
    insomnia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    1
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    blood creatinine increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    2
    blood potassium decreased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    creatinine renal clearance decreased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    1
    lipase increased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    platelet count decreased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    weight decreased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    6 / 14 (42.86%)
         occurrences all number
    0
    2
    7
    white blood cell count decreased
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    Injury, poisoning and procedural complications
    fall
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    post procedural inflammation
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    sunburn
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    tooth fracture
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    wound
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    angina pectoris
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    tachycardia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    aphasia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    cognitive disorder
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    dizziness
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    3 / 14 (21.43%)
         occurrences all number
    1
    1
    4
    dizziness postural
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    dysgeusia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 6 (66.67%)
    4 / 6 (66.67%)
    8 / 14 (57.14%)
         occurrences all number
    4
    4
    9
    dyskinesia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    head discomfort
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    neuropathy peripheral
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    paraesthesia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    2
    peripheral sensory neuropathy
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    1
    1
    0
    somnolence
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    syncope
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    2
    transient ischaemic attack
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    tremor
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 6 (33.33%)
    3 / 6 (50.00%)
    8 / 14 (57.14%)
         occurrences all number
    3
    5
    12
    febrile neutropenia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    neutropenia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    5 / 6 (83.33%)
    5 / 6 (83.33%)
    7 / 14 (50.00%)
         occurrences all number
    9
    8
    13
    thrombocytopenia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 6 (50.00%)
    3 / 6 (50.00%)
    8 / 14 (57.14%)
         occurrences all number
    6
    3
    14
    thrombocytosis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    Ear and labyrinth disorders
    ear pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    Eye disorders
    diplopia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    eyelid ptosis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    visual acuity reduced
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 14 (0.00%)
         occurrences all number
    0
    2
    0
    visual impairment
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    Gastrointestinal disorders
    abdominal discomfort
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    2
    abdominal pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
         occurrences all number
    0
    2
    2
    abdominal pain upper
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    constipation
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 6 (66.67%)
    1 / 6 (16.67%)
    8 / 14 (57.14%)
         occurrences all number
    4
    1
    10
    diarrhoea
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    6 / 14 (42.86%)
         occurrences all number
    1
    1
    11
    dyspepsia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    2
    haematemesis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    intestinal ischaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    mouth ulceration
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    1
    nausea
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 6 (33.33%)
    4 / 6 (66.67%)
    10 / 14 (71.43%)
         occurrences all number
    2
    5
    13
    paraesthesia oral
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    rectal haemorrhage
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    stomatitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
         occurrences all number
    0
    3
    2
    vomiting
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 6 (33.33%)
    4 / 6 (66.67%)
    5 / 14 (35.71%)
         occurrences all number
    5
    6
    9
    Skin and subcutaneous tissue disorders
    alopecia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    7 / 14 (50.00%)
         occurrences all number
    3
    2
    7
    cold sweat
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    dry skin
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    3 / 14 (21.43%)
         occurrences all number
    0
    1
    3
    ecchymosis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    hyperhidrosis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    night sweats
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    petechiae
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    skin discolouration
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    skin plaque
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    Renal and urinary disorders
    dysuria
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    haematuria
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    1
    back pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    1
    0
    1
    bone pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    muscle spasms
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    4 / 6 (66.67%)
    2 / 6 (33.33%)
    6 / 14 (42.86%)
         occurrences all number
    5
    3
    7
    muscular weakness
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    1
    0
    2
    musculoskeletal chest pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    musculoskeletal pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    myalgia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    neck pain
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    1
    pain in extremity
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    1
    Infections and infestations
    cellulitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    escherichia urinary tract infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    folliculitis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    furuncle
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    gastrointestinal viral infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    lower respiratory tract infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    oral candidiasis
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    pneumonia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    rash pustular
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    skin infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    tinea cruris
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    1
    upper respiratory tract infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    urinary tract infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    0
    2
    urinary tract infection bacterial
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    0
    viral infection
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    0
    2
    Metabolism and nutrition disorders
    decreased appetite
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    3 / 6 (50.00%)
    3 / 6 (50.00%)
    6 / 14 (42.86%)
         occurrences all number
    3
    3
    7
    dehydration
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    2
    3
    0
    failure to thrive
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    hypercalcaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    hypokalaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    3 / 14 (21.43%)
         occurrences all number
    1
    1
    3
    hypomagnesaemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    2 / 14 (14.29%)
         occurrences all number
    3
    1
    2
    hyponatraemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    1
    hypophagia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 14 (0.00%)
         occurrences all number
    0
    1
    0
    hypophosphataemia
    alternative dictionary used: MedDRA 18.0
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    1
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This event is gender specific, only occurring in male or female subjects. The number of subjects exposed has been adjusted accordingly.

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 May 2013
    Amendment b : - The restriction for use of colony-stimulating factors (CSFs) during Cycle 1 was changed to allow use according to ASCO guidelines based on investigator feedback regarding clinical practice for carboplatin and etoposide therapy . - Changes were made to the dose reduction tables based on investigator feedback regarding clinical practice for carboplatin and etoposide therapy. - Wording was added regarding the use of 2 forms of medically approved contraception based on emerging animal toxicity data. - The metabolite identification number was corrected throughout the document. - Wording was added regarding the use of the patient diary.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Due to strategic reasons, the Phase 2 portion was not initiated, and further clinical development was stopped.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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