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    Clinical Trial Results:
    A Randomized, Open-Label, Phase 2 Study of Abemaciclib plus Tamoxifen or Abemaciclib Alone, in Women with Previously Treated Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer

    Summary
    EudraCT number
    2016-000288-18
    Trial protocol
    ES   AT   BE   DE   CZ   FR  
    Global end of trial date

    Results information
    Results version number
    v1(current)
    This version publication date
    25 Jun 2022
    First version publication date
    25 Jun 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    I3Y-MC-JPCG
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02747004
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    Trial Number: 16339
    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 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
    Interim
    Date of interim/final analysis
    15 Jun 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    15 Jun 2018
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    The main purpose of this study is to evaluate the safety and efficacy of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), metastatic breast cancer.
    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
    14 Sep 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 4
    Country: Number of subjects enrolled
    France: 6
    Country: Number of subjects enrolled
    Argentina: 16
    Country: Number of subjects enrolled
    Brazil: 22
    Country: Number of subjects enrolled
    Mexico: 15
    Country: Number of subjects enrolled
    Taiwan: 23
    Country: Number of subjects enrolled
    United States: 9
    Country: Number of subjects enrolled
    Czechia: 16
    Country: Number of subjects enrolled
    Germany: 5
    Country: Number of subjects enrolled
    Italy: 11
    Country: Number of subjects enrolled
    Spain: 47
    Country: Number of subjects enrolled
    Belgium: 12
    Country: Number of subjects enrolled
    Russian Federation: 16
    Country: Number of subjects enrolled
    Turkey: 32
    Worldwide total number of subjects
    234
    EEA total number of subjects
    101
    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)
    175
    From 65 to 84 years
    59
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Final results will be posted after the study completion once trial achieves global end date (Last patient visit: LPV).

    Pre-assignment
    Screening details
    Not Applicable.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen
    Arm description
    Participants received oral dose of 150 mg Abemaciclib every 12 hours (Q12H) along with 20mg Tamoxifen every 24 hours (QD) on days 1 to days 28 of a 28 day cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    LY2835219
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg Abemaciclib given Q12H on days 1 to days 28 of a 28 day cycle.

    Investigational medicinal product name
    Tamoxifen
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    20mg tamoxifen QD on days 1 to days 28 of a 28 day cycle.

    Arm title
    150mg Abemaciclib
    Arm description
    Participants received oral dose of 150 milligrams (mg) Abemaciclib every 12 hours (Q12H) on days 1 to days 28 of a 28 day cycle.
    Arm type
    Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    LY2835219
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    150 mg Abemaciclib Q12H on days 1 to days 28 of a 28 day cycle.

    Arm title
    200mg Abemaciclib + 2mg Prophylactic Loperamide
    Arm description
    Participants received oral dose of 200 milligrams (mg) Abemaciclib every 12 hours (Q12H) along with 2mg Prophylactic Loperamide on days 1 to days 28 of a 28 day cycle. Note: During Cycle 1, 2mg prophylactic loperamide was administered orally with the first dose of abemaciclib daily. During Cycle 2 and beyond, loperamide was administered at investigator’s discretion and/or if clinically indicated.
    Arm type
    Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    LY2835219
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    200 mg Abemaciclib Q12H on days 1 to days 28 of a 28 day cycle.

    Investigational medicinal product name
    Loperamide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    2mg Prophylactic Loperamide on days 1 to days 28 of a 28 day cycle. Note: During Cycle 1, 2mg prophylactic loperamide was administered orally with the first dose of abemaciclib daily. During Cycle 2 and beyond, loperamide was administered at investigator’s discretion and/or if clinically indicated.

    Number of subjects in period 1
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Started
    78
    79
    77
    Received at least one dose of study drug
    78
    79
    77
    Completed
    21
    30
    30
    Not completed
    57
    49
    47
         on study treatment/follow-up
    48
    42
    41
         Consent withdrawn by subject
    8
    5
    4
         Lost to follow-up
    1
    2
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen
    Reporting group description
    Participants received oral dose of 150 mg Abemaciclib every 12 hours (Q12H) along with 20mg Tamoxifen every 24 hours (QD) on days 1 to days 28 of a 28 day cycle.

    Reporting group title
    150mg Abemaciclib
    Reporting group description
    Participants received oral dose of 150 milligrams (mg) Abemaciclib every 12 hours (Q12H) on days 1 to days 28 of a 28 day cycle.

    Reporting group title
    200mg Abemaciclib + 2mg Prophylactic Loperamide
    Reporting group description
    Participants received oral dose of 200 milligrams (mg) Abemaciclib every 12 hours (Q12H) along with 2mg Prophylactic Loperamide on days 1 to days 28 of a 28 day cycle. Note: During Cycle 1, 2mg prophylactic loperamide was administered orally with the first dose of abemaciclib daily. During Cycle 2 and beyond, loperamide was administered at investigator’s discretion and/or if clinically indicated.

    Reporting group values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide Total
    Number of subjects
    78 79 77 234
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    54.28 ± 12.47 56.18 ± 12.24 55.86 ± 11.03 -
    Gender categorical
    Units: Subjects
        Female
    78 79 77 234
        Male
    0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    16 20 21 57
        Not Hispanic or Latino
    55 45 46 146
        Unknown or Not Reported
    7 14 10 31
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    4 3 4 11
        Asian
    8 6 10 24
        Native Hawaiian or Other Pacific Islander
    0 0 0 0
        Black or African American
    2 1 2 5
        White
    63 64 60 187
        More than one race
    0 1 0 1
        Unknown or Not Reported
    1 4 1 6

    End points

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    End points reporting groups
    Reporting group title
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen
    Reporting group description
    Participants received oral dose of 150 mg Abemaciclib every 12 hours (Q12H) along with 20mg Tamoxifen every 24 hours (QD) on days 1 to days 28 of a 28 day cycle.

    Reporting group title
    150mg Abemaciclib
    Reporting group description
    Participants received oral dose of 150 milligrams (mg) Abemaciclib every 12 hours (Q12H) on days 1 to days 28 of a 28 day cycle.

    Reporting group title
    200mg Abemaciclib + 2mg Prophylactic Loperamide
    Reporting group description
    Participants received oral dose of 200 milligrams (mg) Abemaciclib every 12 hours (Q12H) along with 2mg Prophylactic Loperamide on days 1 to days 28 of a 28 day cycle. Note: During Cycle 1, 2mg prophylactic loperamide was administered orally with the first dose of abemaciclib daily. During Cycle 2 and beyond, loperamide was administered at investigator’s discretion and/or if clinically indicated.

    Primary: Progression Free Survival (PFS)

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    End point title
    Progression Free Survival (PFS)
    End point description
    Progression-free survival time was measured from the date of randomization to the date of investigator-determined objective progression as defined by RECIST v1.1, or death from any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post baseline radiographic assessment is available. Analysis population description (APD) included all randomized participants who received at least one dose of study drug. Censored participants: 21 in Abemaciclib 150 mg + Tamoxifen 20mg; 25 in Abemaciclib 150 mg; 22 in Abemaciclib 200mg.
    End point type
    Primary
    End point timeframe
    Baseline to Objective Disease Progression or Death from Any Cause (Up to 21 Months)
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Number of subjects analysed
    78
    79
    77
    Units: Months
        median (confidence interval 95%)
    9.07 (6.90 to 10.95)
    6.48 (4.77 to 9.21)
    7.43 (5.42 to 9.17)
    Statistical analysis title
    PFS: Statistical analysis 1
    Comparison groups
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen v 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Number of subjects included in analysis
    155
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.293 [1]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    0.815
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.556
         upper limit
    1.193
    Notes
    [1] - Two-sided P-value. Stratified by the randomization factors of presence of liver metastases and prior use of Tamoxifen in the advanced/metastatic setting
    Statistical analysis title
    PFS: Statistical analysis 2
    Comparison groups
    200mg Abemaciclib + 2mg Prophylactic Loperamide v 150mg Abemaciclib
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    other [2]
    P-value
    = 0.8109 [3]
    Method
    Logrank
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.045
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.711
         upper limit
    1.535
    Notes
    [2] - Informal phase 2 non-inferiority.
    [3] - Stratified by the randomization factors of presence of liver metastases and prior use of Tamoxifen in the advanced/metastatic setting.

    Secondary: Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR)

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    End point title
    Objective Response Rate (ORR): Percentage of Participants with a Complete Response (CR) or Partial Response (PR)
    End point description
    Objective response rate was defined as the percentage of participants with CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD (longest diameter) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. APD included all randomized participants who received at least one dose of study drug and had PR/CR data.
    End point type
    Secondary
    End point timeframe
    Baseline to Objective Disease Progression (Up to 21 Months)
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Number of subjects analysed
    78
    79
    77
    Units: Percentage of participants
        number (confidence interval 95%)
    34.6 (24.1 to 45.2)
    24.1 (14.6 to 33.5)
    32.5 (22 to 42.9)
    No statistical analyses for this end point

    Secondary: Duration of Response (DoR)

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    End point title
    Duration of Response (DoR)
    End point description
    DoR is defined as the time from the date of first evidence of a CR or PR to the date of objective progression or death from any cause, whichever is earlier as defined by Recist v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. APD included all randomized participants who received at least one dose of study drug and achieved CR or PR. Censored participants: 9 in Abemaciclib 150 mg + Tamoxifen 20mg; 9 in Abemaciclib 150 mg; 11 in Abemaciclib 200mg.
    End point type
    Secondary
    End point timeframe
    Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 21 Months)
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Number of subjects analysed
    27
    19 [4]
    25
    Units: Months
        median (confidence interval 95%)
    7.40 (3.88 to 9.27)
    9.21 (3.72 to 9999)
    7.46 (5.56 to 10.92)
    Notes
    [4] - 9999=Data Not Available (N/A): Upper bound not estimable.
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK): Mean Single Dose Concentration of Abemaciclib and its Metabolites

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    End point title
    Pharmacokinetics (PK): Mean Single Dose Concentration of Abemaciclib and its Metabolites
    End point description
    Mean single dose concentrations of Abemaciclib and its metabolites (M2 & M20) are reported. APD included all randomized participants who received at least one dose of study drug and had evaluable PK samples.
    End point type
    Secondary
    End point timeframe
    Cycle (C) 1 Day (D) 1 post dose
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Number of subjects analysed
    19
    13
    20
    Units: Nanogram per Millilitre (ng/mL)
    geometric mean (geometric coefficient of variation)
        Abemaciclib (C1D1)
    10.9 ± 231
    3.05 ± 95.4
    8.59 ± 440
        M2 (C1D1)
    6.05 ± 123
    2.14 ± 60.1
    6.85 ± 237
        M20 (C1D1)
    6.50 ± 132
    2.54 ± 54.5
    7.91 ± 220
    No statistical analyses for this end point

    Secondary: Pharmacokinetics (PK): Steady State Concentration of Abemaciclib and its Metabolites

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    End point title
    Pharmacokinetics (PK): Steady State Concentration of Abemaciclib and its Metabolites
    End point description
    Mean steady state concentrations of Abemaciclib and its metabolites (M2 & M20) are reported. APD included all randomized participants who received at least one dose of study drug and had evaluable PK samples.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Number of subjects analysed
    55
    56
    46
    Units: Nanogram per Millilitre (ng/mL)
    geometric mean (geometric coefficient of variation)
        Abemaciclib (C1D15)
    214 ± 66.4
    256 ± 58.8
    314 ± 74.3
        M2 (C1D15)
    96.5 ± 53.9
    108 ± 45.6
    147 ± 47.1
        M20 (C1D15)
    180 ± 51.1
    199 ± 41.0
    251 ± 48.5
        Abemaciclib (C2D1)
    98.9 ± 196
    182 ± 129
    220 ± 154
        M2 (C2D1)
    56.1 ± 88.0
    85.4 ± 62.1
    105 ± 98.5
        M20 (C2D1)
    100 ± 103
    149 ± 78.9
    164 ± 171
        Abemaciclib (C2D15)
    135 ± 115
    157 ± 173
    175 ± 136
        M2 (C2D15)
    62.3 ± 79.0
    71.7 ± 97.9
    95.4 ± 73.9
        M20 (C2D15)
    120 ± 76.2
    128 ± 121
    154 ± 101
        Abemaciclib (C3D1)
    125 ± 64.3
    177 ± 42.0
    207 ± 49
        M2 (C3D1)
    60.6 ± 39.6
    78.4 ± 38.2
    95.8 ± 44.2
        M20 (C3D1)
    109 ± 39.4
    146 ± 37.7
    171 ± 36.6
    No statistical analyses for this end point

    Secondary: PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen

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    End point title
    PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen [5]
    End point description
    Mean single dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported. APD included all randomized participants who received at least one dose of study drug along with Tamoxifen and had evaluable PK samples. 9999=Data Not Available (N/A): Geometric Mean was not able to be calculated due to small sample size (2 Participants).
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 post dose
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Descriptive statistics was added in only specific baseline period reporting arms with evaluable PK data.
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen
    Number of subjects analysed
    21 [6]
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Tamoxifen (C1D1)
    7.47 ± 116
        Endoxifen (C1D1)
    9999 ± 9999
    Notes
    [6] - Endoxifen (C1D1): n = 2; Individual values = 0.653 ng/mL, 3.8 ng/mL.
    No statistical analyses for this end point

    Secondary: PK: Multiple Dose Concentration of Tamoxifen and Endoxifen

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    End point title
    PK: Multiple Dose Concentration of Tamoxifen and Endoxifen [7]
    End point description
    Mean multiple dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported. APD included all randomized participants who received at least one dose of study drug along with Tamoxifen and had evaluable PK samples.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Descriptive statistics was added in only specific baseline period reporting arms with evaluable PK data.
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen
    Number of subjects analysed
    48
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Tamoxifen (C1D15)
    84.5 ± 41.6
        Endoxifen (C1D15)
    4.76 ± 99.7
        Tamoxifen (C2D1)
    98.7 ± 50.2
        Endoxifen (C2D1)
    7.41 ± 89.5
        Tamoxifen (C2D15)
    109 ± 51.9
        Endoxifen (C2D15)
    9.17 ± 73.7
        Tamoxifen (C3D1)
    112 ± 60.2
        Endoxifen (C3D1)
    10.3 ± 84.8
    No statistical analyses for this end point

    Secondary: Change from Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)

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    End point title
    Change from Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
    End point description
    The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions: 1) Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent). 2) Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much) 3) Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much). Raw scores are linearly converted to a 0–100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden. APD included all randomized participants who received at least one dose of study drug with baseline and post-baseline EORTC QLQ-C30 score.
    End point type
    Secondary
    End point timeframe
    Baseline, 21 Months
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Number of subjects analysed
    77
    75
    76
    Units: score on a scale
    least squares mean (standard deviation)
        Global Health Status
    1.56 ± 1.83
    4.56 ± 1.90
    -2.77 ± 1.91
        Functional Scales (Physical Functioning)
    -2.01 ± 1.59
    -1.05 ± 1.68
    -2.65 ± 1.68
        Functional Scales (Role Functioning)
    -0.44 ± 2.18
    -3.95 ± 2.30
    -5.87 ± 2.29
        Functional Scales (Emotional Functioning)
    4.40 ± 1.88
    2.58 ± 1.95
    1.86 ± 1.95
        Functional Scale (Cognitive Functioning)
    0.14 ± 1.37
    -1.31 ± 1.44
    -2.39 ± 1.43
        Functional Scales (Social Functioning)
    3.23 ± 2.08
    -0.53 ± 2.16
    -0.94 ± 2.16
        Symptom Scales (Fatigue)
    2.39 ± 2.05
    2.77 ± 2.15
    4.0 ± 2.16
        Symptom Scales (Nausea and Vomiting)
    5.59 ± 1.63
    5.30 ± 1.73
    5.09 ± 1.71
        Symptom Scales (Pain)
    -3.09 ± 2.20
    -1.43 ± 2.30
    -2.01 ± 2.29
        Symptom Scales (Dyspnoea)
    4.21 ± 1.79
    -3.49 ± 1.89
    -2.0 ± 1.87
        Symptom Scales (Insomnia)
    -5.02 ± 2.21
    -3.43 ± 2.36
    -2.98 ± 2.35
        Symptom Scales (Appetite Loss)
    5.82 ± 2.38
    1.87 ± 2.50
    7.76 ± 2.50
        Symptom Scales (Constipation)
    -0.28 ± 1.57
    -6.29 ± 1.71
    0.08 ± 1.67
        Symptom Scales (Diarrhoea)
    13.31 ± 1.97
    20.17 ± 2.10
    17.43 ± 2.09
        Symptom Scales (Functional Difficulties)
    -7.56 ± 2.00
    -3.81 ± 2.08
    -0.09 ± 2.07
    No statistical analyses for this end point

    Secondary: Change from Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)

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    End point title
    Change from Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)
    End point description
    mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours and typical completion time for this instrument is less than 5 minutes. APD included all randomized participants who received at least one dose of study drug and had baselines and post baseline mBPI-sf measurement.
    End point type
    Secondary
    End point timeframe
    Baseline, 21 Months
    End point values
    150 milligram (mg) Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Number of subjects analysed
    78
    76
    75
    Units: score on a scale
    least squares mean (standard deviation)
        Pain at its Worst in Last 24 Hours
    -0.53 ± 0.20
    -0.43 ± 0.21
    -0.43 ± 0.21
        Pain at its Least in Last 24 Hours
    -0.09 ± 0.15
    -0.01 ± 0.16
    0.14 ± 0.16
        Pain on the Average
    -0.34 ± 0.16
    -0.20 ± 0.17
    -0.11 ± 0.17
        Pain Right Now
    -0.28 ± 0.17
    -0.18 ± 0.17
    -0.04 ± 0.17
        Mean Interference Score
    -0.09 ± 0.18
    0.03 ± 0.18
    0.16 ± 0.18
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 21 Months
    Adverse event reporting additional description
    All randomized participants who received at least one dose of study drug.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    150mg Abemaciclib + 20mg Tamoxifen
    Reporting group description
    Participants received oral dose of 150 milligrams (mg) Abemaciclib every 12 hours (Q12H) along with 20mg Tamoxifen every 24 hours (QD) on days 1 to days 28 of a 28 day cycle.

    Reporting group title
    150mg Abemaciclib
    Reporting group description
    Participants received oral dose of 150 milligrams (mg) Abemaciclib every 12 hours (Q12H) on days 1 to days 28 of a 28 day cycle.

    Reporting group title
    200mg Abemaciclib + 2mg Prophylactic Loperamide
    Reporting group description
    Participants received oral dose of 200 milligrams (mg) Abemaciclib every 12 hours (Q12H) along with 2mg Prophylactic Loperamide on days 1 to days 28 of a 28 day cycle. Note: During Cycle 1, 2mg prophylactic loperamide was administered orally with the first dose of abemaciclib daily. During Cycle 2 and beyond, loperamide was administered at investigator's discretion and/or if clinically indicated.

    Serious adverse events
    150mg Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 78 (20.51%)
    16 / 79 (20.25%)
    21 / 77 (27.27%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    deep vein thrombosis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    hypertensive crisis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    blood creatinine increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    haemoglobin decreased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    neutrophil count decreased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    acute coronary syndrome
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         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 arrest
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    cardio-respiratory arrest
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    dyspnoea
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    2 / 79 (2.53%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pleural effusion
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    0 / 77 (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
    pneumonia aspiration
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    pneumonitis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (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
    pneumothorax
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pulmonary embolism
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    2 / 78 (2.56%)
    2 / 79 (2.53%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pulmonary oedema
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 79 (1.27%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    disseminated intravascular coagulation
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    haemolytic anaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (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
    leukopenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    3 / 79 (3.80%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    neutropenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    2 / 79 (2.53%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pancytopenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    thrombocytopenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    2 / 79 (2.53%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    cerebral ischaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    ischaemic stroke
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (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
    monoparesis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    paraesthesia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (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
    spinal cord compression
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    0 / 77 (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
    asthenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    fatigue
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    multiple organ dysfunction syndrome
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    pain
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pyrexia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    2 / 79 (2.53%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    constipation
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    diarrhoea
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 79 (1.27%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    dyspepsia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    gastrointestinal toxicity
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    intestinal obstruction
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    nausea
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    2 / 77 (2.60%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    vomiting
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 79 (1.27%)
    2 / 77 (2.60%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    cholangitis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    0 / 77 (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
    hepatic failure
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 79 (1.27%)
    0 / 77 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    acute kidney injury
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 79 (1.27%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    glomerulonephritis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    dehydration
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (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
    hypercalcaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    0 / 77 (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
    hyponatraemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (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
    Infections and infestations
    influenza
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    lung infection
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pharyngitis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    pneumonia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    respiratory tract infection
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (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
    sepsis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    1 / 79 (1.27%)
    0 / 77 (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
    upper respiratory tract infection
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    urinary tract infection
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    viral infection
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         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
    150mg Abemaciclib + 20mg Tamoxifen 150mg Abemaciclib 200mg Abemaciclib + 2mg Prophylactic Loperamide
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    73 / 78 (93.59%)
    77 / 79 (97.47%)
    75 / 77 (97.40%)
    Vascular disorders
    hot flush
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    6 / 78 (7.69%)
    2 / 79 (2.53%)
    1 / 77 (1.30%)
         occurrences all number
    9
    2
    2
    General disorders and administration site conditions
    asthenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    14 / 78 (17.95%)
    14 / 79 (17.72%)
    6 / 77 (7.79%)
         occurrences all number
    26
    20
    7
    fatigue
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    22 / 78 (28.21%)
    17 / 79 (21.52%)
    21 / 77 (27.27%)
         occurrences all number
    32
    30
    41
    mucosal inflammation
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    5 / 78 (6.41%)
    3 / 79 (3.80%)
    2 / 77 (2.60%)
         occurrences all number
    8
    4
    2
    oedema peripheral
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    3 / 78 (3.85%)
    6 / 79 (7.59%)
    7 / 77 (9.09%)
         occurrences all number
    4
    8
    7
    pyrexia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    7 / 78 (8.97%)
    5 / 79 (6.33%)
    8 / 77 (10.39%)
         occurrences all number
    8
    7
    8
    Psychiatric disorders
    anxiety
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    5 / 79 (6.33%)
    2 / 77 (2.60%)
         occurrences all number
    0
    5
    2
    insomnia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 79 (2.53%)
    5 / 77 (6.49%)
         occurrences all number
    3
    2
    5
    Investigations
    alanine aminotransferase increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    6 / 78 (7.69%)
    4 / 79 (5.06%)
    5 / 77 (6.49%)
         occurrences all number
    10
    6
    8
    aspartate aminotransferase increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    8 / 78 (10.26%)
    4 / 79 (5.06%)
    7 / 77 (9.09%)
         occurrences all number
    12
    5
    8
    blood alkaline phosphatase increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    3 / 79 (3.80%)
    4 / 77 (5.19%)
         occurrences all number
    10
    4
    4
    blood creatinine increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    14 / 78 (17.95%)
    7 / 79 (8.86%)
    8 / 77 (10.39%)
         occurrences all number
    35
    15
    11
    gamma-glutamyltransferase increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    3 / 78 (3.85%)
    5 / 79 (6.33%)
    3 / 77 (3.90%)
         occurrences all number
    5
    13
    7
    lymphocyte count decreased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    5 / 79 (6.33%)
    3 / 77 (3.90%)
         occurrences all number
    1
    20
    4
    platelet count decreased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    8 / 78 (10.26%)
    9 / 79 (11.39%)
    22 / 77 (28.57%)
         occurrences all number
    14
    22
    49
    neutrophil count decreased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    11 / 78 (14.10%)
    21 / 79 (26.58%)
    22 / 77 (28.57%)
         occurrences all number
    22
    71
    81
    weight decreased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    5 / 78 (6.41%)
    9 / 79 (11.39%)
    5 / 77 (6.49%)
         occurrences all number
    9
    10
    6
    white blood cell count decreased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    12 / 78 (15.38%)
    18 / 79 (22.78%)
    15 / 77 (19.48%)
         occurrences all number
    26
    56
    52
    Blood and lymphatic system disorders
    anaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    30 / 78 (38.46%)
    24 / 79 (30.38%)
    31 / 77 (40.26%)
         occurrences all number
    63
    36
    68
    leukopenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    9 / 78 (11.54%)
    10 / 79 (12.66%)
    6 / 77 (7.79%)
         occurrences all number
    24
    23
    9
    neutropenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    21 / 78 (26.92%)
    20 / 79 (25.32%)
    18 / 77 (23.38%)
         occurrences all number
    64
    46
    51
    thrombocytopenia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    8 / 78 (10.26%)
    1 / 79 (1.27%)
    5 / 77 (6.49%)
         occurrences all number
    18
    1
    5
    Respiratory, thoracic and mediastinal disorders
    cough
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    7 / 78 (8.97%)
    7 / 79 (8.86%)
    10 / 77 (12.99%)
         occurrences all number
    8
    7
    14
    dyspnoea
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    8 / 78 (10.26%)
    12 / 79 (15.19%)
    5 / 77 (6.49%)
         occurrences all number
    9
    15
    10
    Nervous system disorders
    dizziness
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    2 / 78 (2.56%)
    5 / 79 (6.33%)
    2 / 77 (2.60%)
         occurrences all number
    2
    7
    2
    dysgeusia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    4 / 79 (5.06%)
    3 / 77 (3.90%)
         occurrences all number
    5
    4
    3
    headache
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    7 / 78 (8.97%)
    6 / 79 (7.59%)
    7 / 77 (9.09%)
         occurrences all number
    11
    7
    7
    paraesthesia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    3 / 78 (3.85%)
    4 / 79 (5.06%)
    3 / 77 (3.90%)
         occurrences all number
    5
    5
    3
    Eye disorders
    dry eye
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    0 / 78 (0.00%)
    4 / 79 (5.06%)
    0 / 77 (0.00%)
         occurrences all number
    0
    4
    0
    lacrimation increased
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    2 / 78 (2.56%)
    6 / 79 (7.59%)
    4 / 77 (5.19%)
         occurrences all number
    2
    7
    5
    Gastrointestinal disorders
    abdominal distension
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    4 / 79 (5.06%)
    3 / 77 (3.90%)
         occurrences all number
    5
    5
    3
    abdominal pain
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    16 / 78 (20.51%)
    11 / 79 (13.92%)
    19 / 77 (24.68%)
         occurrences all number
    21
    17
    21
    abdominal pain upper
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    6 / 78 (7.69%)
    8 / 79 (10.13%)
    6 / 77 (7.79%)
         occurrences all number
    7
    10
    7
    constipation
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    10 / 78 (12.82%)
    9 / 79 (11.39%)
    25 / 77 (32.47%)
         occurrences all number
    16
    13
    28
    diarrhoea
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    41 / 78 (52.56%)
    53 / 79 (67.09%)
    47 / 77 (61.04%)
         occurrences all number
    161
    244
    140
    dyspepsia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    7 / 78 (8.97%)
    3 / 79 (3.80%)
    4 / 77 (5.19%)
         occurrences all number
    7
    3
    6
    flatulence
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 79 (1.27%)
    3 / 77 (3.90%)
         occurrences all number
    5
    1
    4
    haemorrhoids
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 79 (1.27%)
    1 / 77 (1.30%)
         occurrences all number
    5
    1
    2
    nausea
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    24 / 78 (30.77%)
    26 / 79 (32.91%)
    33 / 77 (42.86%)
         occurrences all number
    48
    47
    50
    stomatitis
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    5 / 78 (6.41%)
    4 / 79 (5.06%)
    4 / 77 (5.19%)
         occurrences all number
    5
    7
    6
    vomiting
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    14 / 78 (17.95%)
    20 / 79 (25.32%)
    20 / 77 (25.97%)
         occurrences all number
    34
    62
    34
    toothache
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    0 / 79 (0.00%)
    0 / 77 (0.00%)
         occurrences all number
    4
    0
    0
    Skin and subcutaneous tissue disorders
    alopecia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    5 / 78 (6.41%)
    8 / 79 (10.13%)
    3 / 77 (3.90%)
         occurrences all number
    5
    9
    3
    pruritus
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    8 / 78 (10.26%)
    6 / 79 (7.59%)
    4 / 77 (5.19%)
         occurrences all number
    8
    7
    4
    Musculoskeletal and connective tissue disorders
    arthralgia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    6 / 78 (7.69%)
    5 / 79 (6.33%)
    1 / 77 (1.30%)
         occurrences all number
    8
    7
    1
    back pain
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    8 / 78 (10.26%)
    11 / 79 (13.92%)
    2 / 77 (2.60%)
         occurrences all number
    9
    14
    3
    bone pain
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    7 / 79 (8.86%)
    0 / 77 (0.00%)
         occurrences all number
    8
    12
    0
    myalgia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    5 / 78 (6.41%)
    2 / 79 (2.53%)
    2 / 77 (2.60%)
         occurrences all number
    7
    2
    2
    musculoskeletal pain
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    2 / 78 (2.56%)
    4 / 79 (5.06%)
    4 / 77 (5.19%)
         occurrences all number
    2
    4
    5
    Metabolism and nutrition disorders
    dehydration
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 79 (0.00%)
    5 / 77 (6.49%)
         occurrences all number
    1
    0
    6
    decreased appetite
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    20 / 78 (25.64%)
    12 / 79 (15.19%)
    17 / 77 (22.08%)
         occurrences all number
    29
    21
    27
    hypertriglyceridaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    10 / 78 (12.82%)
    3 / 79 (3.80%)
    2 / 77 (2.60%)
         occurrences all number
    22
    3
    4
    hypokalaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    3 / 78 (3.85%)
    8 / 79 (10.13%)
    9 / 77 (11.69%)
         occurrences all number
    4
    11
    10
    hypocalcaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    2 / 79 (2.53%)
    1 / 77 (1.30%)
         occurrences all number
    5
    2
    1
    hypoalbuminaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    6 / 78 (7.69%)
    3 / 79 (3.80%)
    6 / 77 (7.79%)
         occurrences all number
    9
    3
    11
    hyperglycaemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    1 / 78 (1.28%)
    5 / 79 (6.33%)
    3 / 77 (3.90%)
         occurrences all number
    1
    6
    3
    hyponatraemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 79 (1.27%)
    2 / 77 (2.60%)
         occurrences all number
    7
    1
    2
    hypophosphataemia
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    5 / 78 (6.41%)
    0 / 79 (0.00%)
    1 / 77 (1.30%)
         occurrences all number
    5
    0
    1
    Infections and infestations
    upper respiratory tract infection
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    10 / 78 (12.82%)
    4 / 79 (5.06%)
    4 / 77 (5.19%)
         occurrences all number
    11
    6
    5
    urinary tract infection
    alternative dictionary used: MedDRA 20.0
         subjects affected / exposed
    7 / 78 (8.97%)
    5 / 79 (6.33%)
    5 / 77 (6.49%)
         occurrences all number
    8
    6
    5

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Jan 2019
    - Inclusion criteria modified; - Safety monitoring information modified for hepatic conditions, renal function and venous thromboembolic events (VTEs); - Cytochromes P450 (CYPs) text updated to align with abemaciclib program information.
    07 Feb 2020
    - Dose modification updated and delay guidance for interstitial lung disease (ILD)/pneumonitis events that aligns with the updated Investigator’s Brochure; - Investigator’s brochure updated.
    08 Mar 2021
    - Dose adjustment criteria updated; - Concomitant therapy information was updated for CYP3A modulators and transporter substrates; -Safety monitoring language was updated to align with current guidance and the IB respectively.

    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.
    None reported
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