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    Clinical Trial Results:
    A Phase II, randomized double-blind study of efficacy and safety of two dose levels of LDE225 in patients with locally advanced or metastatic basal cell carcinoma EMA directed use of 999999 as the EU results system will not accept “not estimable”. Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.

    Summary
    EudraCT number
    		 2010-022629-14
    Trial protocol
    		 DE   BE   GR   GB   ES   NL   HU   IT  
    Global end of trial date
    17 Jan 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Jul 2019
    First version publication date
    14 Jul 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CLDE225A2201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01327053
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma, AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma, AG, +41 613241111, Novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma, AG, +41 613241111, Novartis.email@novartis.com
    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
    17 Jan 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Jan 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective was to evaluate the efficacy of sonidegib as measured by the objective response rate (ORR).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    20 Jul 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 12
    Country: Number of subjects enrolled
    Belgium: 20
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    France: 19
    Country: Number of subjects enrolled
    Germany: 49
    Country: Number of subjects enrolled
    Greece: 5
    Country: Number of subjects enrolled
    Hungary: 5
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Switzerland: 6
    Country: Number of subjects enrolled
    United Kingdom: 18
    Country: Number of subjects enrolled
    United States: 87
    Worldwide total number of subjects
    230
    EEA total number of subjects
    122
    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)
    105
    From 65 to 84 years
    125
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Randomization was stratified across the two treatment arms according to the stage of disease (laBCC or mBCC), histological subtype (non-aggressive or aggressive for laBCC patients) and the regions (Australia, Europe, and North America).

    Pre-assignment
    Screening details
    		 All eligible, enrolled patients were randomized in 1:2 ratio to sonidegib treatment with either 200 mg or 800 mg once-daily dose. In total, 230 patients were evaluated as FAS population: 79 and 151 patients randomized to 200mg and 800 mg sonidegib respectively. However, 1 patient randomized to 800 mg sonidegib did not receive study treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 LDE225 (sonidegib) 200 mg
    Arm description
    		 The study is double blinded and will enroll at least 50 evaluable patients in the 200 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sonidegib
    Investigational medicinal product code
    LDE225
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Sonidegib was administered orally, on a continuous once-daily schedule, at a dose of 200 mg. The 200-mg arm received 1 sonidegib capsule+3 placebo capsules.

    Investigational medicinal product name
    Sonidegib Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Sonidegib placebo was administered orally, on a continuous once-daily schedule, at a dose of 200 mg. The 200-mg arm received 1 sonidegib capsule+3 placebo capsules. Placebo was formulated to be indistinguishable from the sonidegib capsules.

    Arm title
    		 LDE225 (sonidegib) 800 mg
    Arm description
    		 The study is double blinded and will enroll at least 100 evaluable patients in the 800 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sonidegib
    Investigational medicinal product code
    LDE225
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Sonidegib was administered orally, on a continuous once-daily schedule, at a dose of 800 mg. The 800-mg arm received 4 capsules of sonidegib.

    Number of subjects in period 1
    		LDE225 (sonidegib) 200 mg LDE225 (sonidegib) 800 mg
    Started
    79
    151
    Untreated
    0
    1
    Patients cont. to next phase of trial
    52
    89
    Survival follow-up
    33
    49
    Post-tretment follow-up
    19
    40
    Completed
    0
    0
    Not completed
    79
    151
         Adverse event, serious fatal
    1
    5
         Physician decision
    10
    14
         Study terminated by Sponsor
    1
    3
         Adverse event, non-fatal
    23
    57
         Non-compliance with study treatment
    -
    5
         Untreated
    -
    1
         Patient/guardian decision
    11
    35
         Lost to follow-up
    2
    4
         Progressive disease
    31
    26
         Protocol deviation
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    LDE225 (sonidegib) 200 mg
    Reporting group description
    		 The study is double blinded and will enroll at least 50 evaluable patients in the 200 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Reporting group title
    LDE225 (sonidegib) 800 mg
    Reporting group description
    		 The study is double blinded and will enroll at least 100 evaluable patients in the 800 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Reporting group values
    		 LDE225 (sonidegib) 200 mg LDE225 (sonidegib) 800 mg Total
    Number of subjects
    		 79 151 230
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 32 73 105
        From 65-84 years
    		 38 67 105
        85 years and over
    		 9 11 20
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 65.6 ± 15.67 63.6 ± 14.59 -
    Sex: Female, Male
    Units: Subjects
        Female
    		 31 55 86
        Male
    		 48 96 144
    Race/Ethnicity, Customized
    Units: Subjects
        Black
    		 0 1 1
        Caucasian
    		 71 145 216
        Other
    		 8 5 13

    End points

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    End points reporting groups
    Reporting group title
    LDE225 (sonidegib) 200 mg
    Reporting group description
    		 The study is double blinded and will enroll at least 50 evaluable patients in the 200 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Reporting group title
    LDE225 (sonidegib) 800 mg
    Reporting group description
    		 The study is double blinded and will enroll at least 100 evaluable patients in the 800 mg LDE225 arm. The efficacy and safety of LDE225 will be analyzed separately in each group. Patients who meet all the inclusion and none of the exclusion criteria will be treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Subject analysis set title
    LDE225 200mg laBCC
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The efficacy and safety of LDE225 200mg laBCC cohort were analyzed separately in each group. Patients who met all the inclusion and none of the exclusion criteria were treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Subject analysis set title
    LDE225 800mg laBCC
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The efficacy and safety of LDE225 800mg laBCC cohort were analyzed separately in each group. Patients who met all the inclusion and none of the exclusion criteria were treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Subject analysis set title
    LDE225 200mg mBCC
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The efficacy and safety of LDE225 200mg mBCC cohort were analyzed separately in each group. Patients who met all the inclusion and none of the exclusion criteria were treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Subject analysis set title
    LDE225 800mg mBCC
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The efficacy and safety of LDE225 800mg mBCC cohort were analyzed separately in each group. Patients who met all the inclusion and none of the exclusion criteria were treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Subject analysis set title
    LDE225 200mg laBCC
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The efficacy and safety of LDE225 200mg laBCC cohort were analyzed separately in each group. Patients who met all the inclusion and none of the exclusion criteria were treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Subject analysis set title
    LDE225 800mg laBCC
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The efficacy and safety of LDE225 800mg laBCC cohort were analyzed separately in each group. Patients who met all the inclusion and none of the exclusion criteria were treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Subject analysis set title
    LDE225 200 mg qd
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients who met all the inclusion and none of the exclusion criteria were treated with 200 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Subject analysis set title
    LDE225 800 mg qd
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Patients who met all the inclusion and none of the exclusion criteria were treated with 800 mg LDE225 daily until disease progression, occurrence of intolerable toxicity, start of another anticancer treatment or withdrawal of consent.

    Primary: Objective response rate (ORR) based on Central Review according to mRECIST (for locally advanced basal cell carcinoma (laBCC)) and RECIST 1.1 (for metastatic basal cell carcinoma (mBCC)) per Primary efficacy analysis set (pEAS)

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    End point title
    		 Objective response rate (ORR) based on Central Review according to mRECIST (for locally advanced basal cell carcinoma (laBCC)) and RECIST 1.1 (for metastatic basal cell carcinoma (mBCC)) per Primary efficacy analysis set (pEAS) [1]
    End point description
    ORR is the percentage of patient’s objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 6 months after starting LDE225 treatment.Treatment with sonidegib was considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Primary
    End point timeframe
    6 months
    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 statistical analysis was planned for this endpoint.
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Percentage of participants
        number (confidence interval 95%)
    42.9 (27.7 to 59.0)
    37.6 (27.8 to 48.3)
    15.4 (1.9 to 45.4)
    17.4 (5.0 to 38.8)
    No statistical analyses for this end point

    Primary: Objective response rate (ORR) based on Central Review according to mRECIST (for locally advanced basal cell carcinoma (laBCC)) and RECIST 1.1 (metastatic basal cell carcinoma (mBCC)) per Full Analysis Set (FAS)

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    End point title
    		 Objective response rate (ORR) based on Central Review according to mRECIST (for locally advanced basal cell carcinoma (laBCC)) and RECIST 1.1 (metastatic basal cell carcinoma (mBCC)) per Full Analysis Set (FAS) [2]
    End point description
    ORR is the percentage of patient’s objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 6 months after starting LDE225 treatment.Treatment with sonidegib was to be considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Primary
    End point timeframe
    6 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: No statistical analysis was planned for this endpoint.
    End point values
    		 LDE225 200mg mBCC LDE225 800mg mBCC LDE225 200mg laBCC LDE225 800mg laBCC
    Number of subjects analysed
    13
    23
    66
    128
    Units: Percentage of participants
        number (confidence interval 95%)
    15.4 (1.9 to 45.4)
    17.4 (5.0 to 38.8)
    47.0 (34.6 to 59.7)
    35.2 (26.9 to 44.1)
    No statistical analyses for this end point

    Secondary: Duration of response (DoR) per Central Review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)

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    End point title
    		 Duration of response (DoR) per Central Review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
    End point description
    Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Progressive disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Months
        median (confidence interval 95%)
    12.9 (9.99 to 999)
    23.7 (10.8 to 29.6)
    24.0 (9.99 to 999)
    999 (9.99 to 999)
    No statistical analyses for this end point

    Secondary: Duration of response (DoR) per Central Review using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)

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    End point title
    		 Duration of response (DoR) per Central Review using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
    End point description
    Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Median DoR for patients with laBCC was non-estimable for both treatment arms. Median DoR was non-estimable for patients with mBCC receiving treatment with sonidegib 200 mg. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg mBCC LDE225 800mg mBCC LDE225 200mg laBCC LDE225 800mg laBCC
    Number of subjects analysed
    13
    23
    66
    128
    Units: Months
        median (confidence interval 95%)
    24.0 (9.9 to 999)
    999 (999 to 999)
    26.1 (9.9 to 999)
    23.3 (12.2 to 29.6)
    No statistical analyses for this end point

    Secondary: Complete response rate (CRR) per Central Review (pEAS)

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    End point title
    		 Complete response rate (CRR) per Central Review (pEAS)
    End point description
    Rate of complete response is the percentage of patients with best overall response of complete response (CR) after starting LDE225 treatment. The rate of CR was determined according to mRECIST for laBCC and RECIST 1.1 for mBCC. Patients with best overall response of ‘Unknown” were treated as non responders. Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Percentage of participants
        number (confidence interval 95%)
    4.8 (0.6 to 16.2)
    2.2 (0.3 to 7.6)
    0.0 (0.0 to 24.7)
    0.0 (0.0 to 14.8)
    No statistical analyses for this end point

    Secondary: Complete response rate (CRR) per Central Review (FAS)

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    End point title
    		 Complete response rate (CRR) per Central Review (FAS)
    End point description
    Rate of complete response is the proportion of patients with best overall response of complete response (CR) after starting LDE225 treatment. The rate of CR will be determined according to mRECIST for laBCC and RECIST 1.1 for mBCC. Patients with best overall response of ‘Unknown” will be treated as non responders
    End point type
    Secondary
    End point timeframe
    6 months
    End point values
    		 LDE225 200mg mBCC LDE225 800mg mBCC LDE225 200mg laBCC LDE225 800mg laBCC
    Number of subjects analysed
    13
    23
    66
    128
    Units: Percentage of participants
        number (confidence interval 95%)
    0.0 (0.0 to 24.7)
    0.0 (0.0 to 14.8)
    3.0 (0.4 to 10.5)
    0.0 (0.0 to 2.8)
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS) per Central review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)

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    End point title
    		 Progression-free survival (PFS) per Central review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
    End point description
    Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Percentage of participants
        median (confidence interval 95%)
    19.0 (9.9 to 999)
    19.4 (13.8 to 30.5)
    13.1 (5.6 to 33.1)
    11.1 (7.3 to 16.6)
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS) per Central review using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)

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    End point title
    		 Progression-free survival (PFS) per Central review using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
    End point description
    Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg mBCC LDE225 800mg mBCC LDE225 200mg laBCC LDE225 800mg laBCC
    Number of subjects analysed
    13
    23
    66
    128
    Units: Percentage of participants
        median (confidence interval 95%)
    13.1 (5.6 to 33.1)
    11.1 (7.3 to 16.6)
    22.1 (9.9 to 999)
    24.9 (19.2 to 33.4)
    No statistical analyses for this end point

    Secondary: Time to tumor response (TTR) per Central review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)

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    End point title
    		 Time to tumor response (TTR) per Central review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
    End point description
    Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Percentage of participants
        median (confidence interval 95%)
    4.0 (3.7 to 5.6)
    3.7 (2.0 to 5.5)
    9.2 (9 to 999)
    1.0 (1.0 to 2.1)
    No statistical analyses for this end point

    Secondary: Time to tumor response (TTR) per Central review using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)

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    End point title
    		 Time to tumor response (TTR) per Central review using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
    End point description
    Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Percentage of participants
        median (confidence interval 95%)
    4.0 (3.7 to 5.6)
    3.7 (2.0 to 5.5)
    9.2 (9 to 999)
    1.0 (1.0 to 2.1)
    No statistical analyses for this end point

    Secondary: Objective response rate (ORR) based on Site Investigator Review according to mRECIST (for locally advanced basal cell carcinoma (laBCC)) and RECIST 1.1 (for metastatic basal cell carcinoma (mBCC)) per Primary efficacy analysis set (pEAS)

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    End point title
    		 Objective response rate (ORR) based on Site Investigator Review according to mRECIST (for locally advanced basal cell carcinoma (laBCC)) and RECIST 1.1 (for metastatic basal cell carcinoma (mBCC)) per Primary efficacy analysis set (pEAS)
    End point description
    ORR is the percentage of patient’s objective response (ORR) by 42 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 42 months after starting LDE225 treatment. Treatment with sonidegib was considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Percentage of participants
        number (confidence interval 95%)
    71.4 (55.4 to 84.3)
    61.3 (50.6 to 71.2)
    23.1 (5.0 to 53.8)
    34.8 (16.4 to 57.3)
    No statistical analyses for this end point

    Secondary: Objective response rate (ORR) based on Site Investigator Review according to mRECIST (for locally advanced basal cell carcinoma (laBCC)) and RECIST 1.1 (metastatic basal cell carcinoma (mBCC)) per Full Analysis Set (FAS)

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    End point title
    		 Objective response rate (ORR) based on Site Investigator Review according to mRECIST (for locally advanced basal cell carcinoma (laBCC)) and RECIST 1.1 (metastatic basal cell carcinoma (mBCC)) per Full Analysis Set (FAS)
    End point description
    ORR is the percentage of patient’s objective response (ORR) by 6 months after starting LDE225 treatment. A responder was defined as a subject with confirmed partial response (PR) or confirmed complete response (CR) 42 months after starting LDE225 treatment.Treatment with sonidegib was to be considered sufficiently efficacious if the observed ORR on any treatment arm at the end of the study was 30% or higher. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg mBCC LDE225 800mg mBCC LDE225 200mg laBCC LDE225 800mg laBCC
    Number of subjects analysed
    13
    23
    66
    128
    Units: Percentage of participants
        number (confidence interval 95%)
    23.1 (5.0 to 53.8)
    34.8 (16.4 to 57.3)
    71.2 (58.7 to 81.7)
    58.6 (49.6 to 67.2)
    No statistical analyses for this end point

    Secondary: Duration of response (DoR) per Site Investigator Review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)

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    End point title
    		 Duration of response (DoR) per Site Investigator Review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
    End point description
    Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Progressive disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Months
        median (confidence interval 95%)
    18.2 (12.9 to 23.0)
    26.0 (15.7 to 47.3)
    18.1 (17.7 to 18.4)
    10.2 (9.9 to 999)
    No statistical analyses for this end point

    Secondary: Duration of response (DoR) per Site Investigatorl Review using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)

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    End point title
    		 Duration of response (DoR) per Site Investigatorl Review using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
    End point description
    Duration of response is the time from the first observed confirmed response (CR or PR) to disease progression or death due to any reason. Median DoR for patients with laBCC was non-estimable for both treatment arms. Median DoR was non-estimable for patients with mBCC receiving treatment with sonidegib 200 mg. Duration of response was for participants with ORR. PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg mBCC LDE225 800mg mBCC LDE225 200mg laBCC LDE225 800mg laBCC
    Number of subjects analysed
    13
    23
    66
    128
    Units: Months
        median (confidence interval 95%)
    18.1 (17.7 to 18.4)
    10.2 (9.9 to 999)
    15.7 (12.0 to 20.2)
    26.0 (18.3 to 47.3)
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS) per Site Investigator review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)

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    End point title
    		 Progression-free survival (PFS) per Site Investigator review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
    End point description
    Progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Percentage of participants
        median (confidence interval 95%)
    20.1 (14.8 to 23.8)
    28.0 (19.4 to 49.8)
    13.1 (9.2 to 19.4)
    14.3 (11.1 to 17.0)
    No statistical analyses for this end point

    Secondary: Time to tumor response (TTR) per Site Investigator review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)

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    End point title
    		 Time to tumor response (TTR) per Site Investigator review using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
    End point description
    Time to tumor response (TTR) is defined as the time from date of enrollment to the date of first documented tumor response (CR or PR). PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
    Number of subjects analysed
    42
    93
    13
    23
    Units: Percentage of participants
        median (confidence interval 95%)
    1.9 (1.8 to 3.9)
    1.8 (1.1 to 2.0)
    1.0 (0.9 to 3.7)
    2.7 (1.0 to 5.6)
    No statistical analyses for this end point

    Secondary: Plasma Concentration of sonidegib (LDE225)

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    End point title
    		 Plasma Concentration of sonidegib (LDE225)
    End point description
    Blood PK samples were collected either by direct venipuncture or an indwelling cannula inserted in a forearm vein for the determination of trough (Cmin) plasma concentrations of sonidegib and its main circulating metabolite, LGE899, from all patients who enrolled in the study. Blood was collected in Weeks 1, 3, 5, 9 (pre-dose), and subsequently pre-dose every 4 weeks up to Week 21, and every 12 weeks thereafter up to week 69.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
    End point values
    		 LDE225 200 mg qd LDE225 800 mg qd
    Number of subjects analysed
    73
    139
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Week 1 (n = 0, 0)
    0 ± 0
    0 ± 0
        Week 3 (n = 66, 128)
    209.91 ± 78.24
    586.76 ± 97.13
        Week 5 (n = 71, 120)
    374.24 ± 68.50
    1012.63 ± 70.42
        Week 9 (n = 68, 101)
    559.29 ± 67.30
    1353.06 ± 63.43
        Week 13 (n = 63, 85)
    714.01 ± 60.79
    1443.84 ± 61.57
        Week 17 (n = 66, 81)
    688.93 ± 64.43
    1594.28 ± 60.77
        Week 21 (n = 59, 68)
    713.13 ± 63.35
    1564.10 ± 64.08
        Week 33 (n = 43, 43)
    663.48 ± 96.19
    1562.73 ± 79.20
        Week 45 (n = 22, 27)
    711.32 ± 46.54
    1433.13 ± 76.91
        Week 57 (n = 13, 17)
    525.53 ± 86.24
    1328.04 ± 69.47
        Wek 69 (n = 6, 11)
    459.10 ± 188.64
    1185.95 ± 118.77
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    OS is defined as the time from date of randomization t date of death due to any cause or the last date that a patient was known to be alive (censored observation) as of the data cut-off.
    End point type
    Secondary
    End point timeframe
    42 months
    End point values
    		 LDE225 200mg mBCC LDE225 800mg mBCC LDE225 200mg laBCC LDE225 800mg laBCC
    Number of subjects analysed
    13
    23
    66
    128
    Units: Participants
    1
    2
    1
    7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 76.2 months.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    LDE225 200 mg qd
    Reporting group description
    		 LDE225 200 mg qd

    Reporting group title
    LDE225 800 mg qd
    Reporting group description
    		 LDE225 800 mg qd

    Serious adverse events
    		 LDE225 200 mg qd LDE225 800 mg qd
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 79 (20.25%)
    58 / 150 (38.67%)
         number of deaths (all causes)
    1
    7
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain neoplasm
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Invasive papillary breast carcinoma
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung neoplasm
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Arterial haemorrhage
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    1 / 79 (1.27%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Cardiac death
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Facial pain
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 79 (1.27%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine prolapse
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bronchitis chronic
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 79 (1.27%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Emphysema
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Rhinorrhoea
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sputum discoloured
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Bipolar disorder
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood creatine phosphokinase MB increased
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 79 (1.27%)
    6 / 150 (4.00%)
         occurrences causally related to treatment / all
    1 / 1
    6 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lipase increased
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myoglobin blood increased
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    1 / 79 (1.27%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fall
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 79 (1.27%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 79 (1.27%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bundle branch block left
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiac failure congestive
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysgeusia
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 79 (1.27%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 79 (0.00%)
    5 / 150 (3.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Chronic gastritis
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal pain
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 79 (0.00%)
    3 / 150 (2.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peptic ulcer perforation
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 79 (0.00%)
    4 / 150 (2.67%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatotoxicity
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Skin lesion
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder obstruction
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephropathy toxic
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Muscle contracture
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myositis
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 79 (1.27%)
    5 / 150 (3.33%)
         occurrences causally related to treatment / all
    1 / 1
    5 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 79 (1.27%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Endocarditis
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mastoiditis
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Parotitis
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 79 (2.53%)
    3 / 150 (2.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pseudomonas infection
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 79 (1.27%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Septic shock
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Superinfection
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 79 (1.27%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 150 (1.33%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 79 (1.27%)
    3 / 150 (2.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Failure to thrive
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 150 (0.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 150 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 LDE225 200 mg qd LDE225 800 mg qd
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    76 / 79 (96.20%)
    145 / 150 (96.67%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma
         subjects affected / exposed
    4 / 79 (5.06%)
    5 / 150 (3.33%)
         occurrences all number
    4
    5
    Vascular disorders
    Hypertension
         subjects affected / exposed
    8 / 79 (10.13%)
    16 / 150 (10.67%)
         occurrences all number
    11
    18
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    10 / 79 (12.66%)
    9 / 150 (6.00%)
         occurrences all number
    14
    12
    Fatigue
         subjects affected / exposed
    26 / 79 (32.91%)
    55 / 150 (36.67%)
         occurrences all number
    31
    70
    Pyrexia
         subjects affected / exposed
    4 / 79 (5.06%)
    5 / 150 (3.33%)
         occurrences all number
    5
    6
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 79 (8.86%)
    11 / 150 (7.33%)
         occurrences all number
    8
    14
    Oropharyngeal pain
         subjects affected / exposed
    4 / 79 (5.06%)
    6 / 150 (4.00%)
         occurrences all number
    6
    6
    Psychiatric disorders
    Depression
         subjects affected / exposed
    5 / 79 (6.33%)
    9 / 150 (6.00%)
         occurrences all number
    6
    9
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    23 / 79 (29.11%)
    54 / 150 (36.00%)
         occurrences all number
    29
    74
    Lipase increased
         subjects affected / exposed
    6 / 79 (7.59%)
    13 / 150 (8.67%)
         occurrences all number
    12
    19
    Weight decreased
         subjects affected / exposed
    24 / 79 (30.38%)
    64 / 150 (42.67%)
         occurrences all number
    25
    70
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    5 / 79 (6.33%)
    5 / 150 (3.33%)
         occurrences all number
    6
    6
    Nervous system disorders
    Ageusia
         subjects affected / exposed
    1 / 79 (1.27%)
    15 / 150 (10.00%)
         occurrences all number
    1
    15
    Dizziness
         subjects affected / exposed
    7 / 79 (8.86%)
    15 / 150 (10.00%)
         occurrences all number
    7
    21
    Dysgeusia
         subjects affected / exposed
    35 / 79 (44.30%)
    89 / 150 (59.33%)
         occurrences all number
    38
    99
    Headache
         subjects affected / exposed
    12 / 79 (15.19%)
    20 / 150 (13.33%)
         occurrences all number
    15
    51
    Hypogeusia
         subjects affected / exposed
    0 / 79 (0.00%)
    9 / 150 (6.00%)
         occurrences all number
    0
    9
    Paraesthesia
         subjects affected / exposed
    4 / 79 (5.06%)
    6 / 150 (4.00%)
         occurrences all number
    4
    6
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 79 (5.06%)
    13 / 150 (8.67%)
         occurrences all number
    4
    20
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 79 (0.00%)
    11 / 150 (7.33%)
         occurrences all number
    0
    12
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    8 / 79 (10.13%)
    9 / 150 (6.00%)
         occurrences all number
    8
    12
    Abdominal pain upper
         subjects affected / exposed
    7 / 79 (8.86%)
    12 / 150 (8.00%)
         occurrences all number
    9
    15
    Constipation
         subjects affected / exposed
    6 / 79 (7.59%)
    24 / 150 (16.00%)
         occurrences all number
    7
    27
    Diarrhoea
         subjects affected / exposed
    25 / 79 (31.65%)
    34 / 150 (22.67%)
         occurrences all number
    43
    46
    Dry mouth
         subjects affected / exposed
    4 / 79 (5.06%)
    8 / 150 (5.33%)
         occurrences all number
    4
    8
    Nausea
         subjects affected / exposed
    31 / 79 (39.24%)
    71 / 150 (47.33%)
         occurrences all number
    45
    106
    Vomiting
         subjects affected / exposed
    9 / 79 (11.39%)
    41 / 150 (27.33%)
         occurrences all number
    14
    63
    Dyspepsia
         subjects affected / exposed
    7 / 79 (8.86%)
    10 / 150 (6.67%)
         occurrences all number
    9
    11
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    39 / 79 (49.37%)
    87 / 150 (58.00%)
         occurrences all number
    41
    91
    Pruritus
         subjects affected / exposed
    6 / 79 (7.59%)
    12 / 150 (8.00%)
         occurrences all number
    7
    12
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    13 / 79 (16.46%)
    17 / 150 (11.33%)
         occurrences all number
    16
    20
    Back pain
         subjects affected / exposed
    6 / 79 (7.59%)
    16 / 150 (10.67%)
         occurrences all number
    6
    18
    Muscle spasms
         subjects affected / exposed
    43 / 79 (54.43%)
    104 / 150 (69.33%)
         occurrences all number
    66
    189
    Muscular weakness
         subjects affected / exposed
    4 / 79 (5.06%)
    8 / 150 (5.33%)
         occurrences all number
    4
    10
    Musculoskeletal pain
         subjects affected / exposed
    4 / 79 (5.06%)
    7 / 150 (4.67%)
         occurrences all number
    4
    7
    Myalgia
         subjects affected / exposed
    15 / 79 (18.99%)
    42 / 150 (28.00%)
         occurrences all number
    18
    53
    Pain in extremity
         subjects affected / exposed
    5 / 79 (6.33%)
    8 / 150 (5.33%)
         occurrences all number
    6
    8
    Infections and infestations
    Influenza
         subjects affected / exposed
    4 / 79 (5.06%)
    8 / 150 (5.33%)
         occurrences all number
    4
    8
    Nasopharyngitis
         subjects affected / exposed
    8 / 79 (10.13%)
    17 / 150 (11.33%)
         occurrences all number
    13
    25
    Pneumonia
         subjects affected / exposed
    4 / 79 (5.06%)
    3 / 150 (2.00%)
         occurrences all number
    4
    3
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 79 (6.33%)
    11 / 150 (7.33%)
         occurrences all number
    5
    12
    Urinary tract infection
         subjects affected / exposed
    7 / 79 (8.86%)
    7 / 150 (4.67%)
         occurrences all number
    19
    15
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    18 / 79 (22.78%)
    52 / 150 (34.67%)
         occurrences all number
    24
    57

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 Apr 2011
    Wording on contraceptive precautions updated: Wording on contraceptive precautions updated To ensure compliance with the UK Guideline of Prevention of Pregnancies in Participants in Clinical Trials
    17 Nov 2011
    - Inclusion criteria modified to clarify eligible patient population: Reasons for ineligibility for local therapies or curative surgery to be collected. - Central histopathological analysis implemented: Initiated for confirmation of diagnosis and eligibility (NB: as a result, a majority of laBCC patients enrolled prior to this ineligible for analysis of ORR per mRECIST) - Central histopathological analysis implemented: Initiated for confirmation of diagnosis and eligibility (NB: as a result, a majority of laBCC patients enrolled prior to this ineligible for analysis of ORR per mRECIST) - Sample size increased from 80 to 100 in 800-mg arm and from 40 to 50 in the 200-mg arm: To collect additional safety and efficacy data - Criteria for assessing ORR amended from RECIST 1.1 to mRECIST for patients with laBCC: Tumor response assessment in patients with laBCC when associated with ulceration, cysts, and scarring/fibrosis are not adequately covered by RECIST 1.1 - Implementation of central reading for determination of primary endpoint: To obtain more robust conclusions
    23 Nov 2011
    Patients experiencing asymptomatic treatment-emergent grade 1 CK elevation to undergo weekly monitoring until resolution: To satisfy local regulatory requirements in France
    28 Jun 2012
    - Introduction of primary efficacy analysis set (pEAS): mRECIST implemented in Amendment 2; consequently, a majority of patients with laBCC enrolled prior to this may not have been eligible for analysis of ORR per mRECIST. The pEAS defined a subset of the full analysis set (FAS) and excluded laBCC patients who were not eligible for tumor assessment per mRECIST. - Sample size further expanded to approximately 210 patients: To ensure a sufficient number of patients in the pEAS (i.e. 50 patients on 200 mg and 100 patients on 800 mg)
    03 Jun 2013
    Statistical analysis for secondary endpoints updated: Allowed ORR according to RECIST 1.1 to be derived for central review data by MRI and photography independently without lesion matching between MRI/photograph and lesions
    14 Nov 2013
    Institution of Independent Review Committee to integrate MRI, photography, and histology data to assess composite overall response: To provide clarification on how the 3 methods of assessment per mRECIST (MRI, color photography, and histology) were to be integrated to determine the composite overall response for patients with laBCC
    04 Apr 2014
    Extension of study duration by further 104 weeks to enable collection of long-term efficacy and safety data: Results of the primary analysis (obtained in Feb-2014) showed both the 200-mg and 800-mg doses to be efficacious and to provide clinical benefit. Data also indicated that both doses were associated with acceptable safety profiles. The IDMC and SSC recommended that the study should continue without change.
    24 Feb 2015
    Updated language regarding the Independent Data Monitoring Committee: To provide clarification regarding the composition of the IDMC.
    16 Mar 2016
    Extension of study treatment for patients receiving clinical benefit post final efficacy analysis: Extension of study treatment for patients receiving clinical benefit post final efficacy analysis: Allowed patients on treatment (post Week 182 following last patient first treatment [LPFT]) who are deriving clinical benefit to continue to receive LDE225 until disease progression, intolerable toxicity, death, or withdrawal of consent. As a result, the visit evaluation schedule and study assessments were modified to be performed according to standard clinical practices post Week 182 following LPFT.

    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.
    230 patients evaluated in the study in the Full Analysis Set: 79 randomized to LDE225 (Sonidegib) 200mg group and 151 randomized to LDE225 800mg group. 1 patient randomized to the 800mg group did not receive study treatment.
    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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