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A Phase II Study of Efficacy and Safety in Patients With Locally Advanced or Metastatic Basal Cell Carcinoma (BOLT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01327053
Recruitment Status : Completed
First Posted : April 1, 2011
Results First Posted : November 23, 2015
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Basal Cell Carcinoma
Intervention Drug: LDE225
Enrollment 230
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 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.
Arm/Group Title LDE225 (Sonidegib) 200 mg LDE225 (Sonidegib) 800 mg
Hide Arm/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. 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.
Period Title: Overall Study
Started 79 151
Untreated 0 1 [1]
Patients Cont. to Next Phase of Trial 52 89
Survival Follow-up 33 49
Post-treatment Follow-up 19 40
Completed 0 0
Not Completed 79 151
Reason Not Completed
Adverse Event             23             57
Patient/guardian decision             11             35
Physician Decision             10             14
Death             1             5
Lost to Follow-up             2             4
Non-compliance with study treatment             0             5
Study terminated by Sponsor             1             3
Progressive disease             31             26
Protocol Violation             0             1
Untreated             0             1
[1]
one patient randomized to LDE225 (sonidegib) 800 mg did not receive study treatment
Arm/Group Title LDE225 (Sonidegib) 200 mg LDE225 (Sonidegib) 800 mg Total
Hide Arm/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. 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. Total of all reporting groups
Overall Number of Baseline Participants 79 151 230
Hide Baseline Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 151 participants 230 participants
65.6  (15.67) 63.6  (14.59) 64.3  (14.96)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 151 participants 230 participants
Female
31
  39.2%
55
  36.4%
86
  37.4%
Male
48
  60.8%
96
  63.6%
144
  62.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 79 participants 151 participants 230 participants
Black 0 1 1
Caucasian 71 145 216
Other 8 5 13
1.Primary Outcome
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)
Hide 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
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)
2.Primary Outcome
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)
Hide 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.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients).
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 66 128 13 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
47.0
(34.6 to 59.7)
35.2
(26.9 to 44.1)
15.4
(1.9 to 45.4)
17.4
(5.0 to 38.8)
3.Secondary Outcome
Title Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Hide 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.

Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
12.9 [1] 
(NA to NA)
23.7
(10.8 to 29.6)
24.0 [1] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
N/A = Both lower and upper confidence intervals were not estimable as limited numbers of PD or death were observed.
[2]
N/A = Median DoR was non-estimable for patients with mBCC receiving treatment with sonidegib 800 mg as limited numbers of PD or death were observed.
4.Secondary Outcome
Title Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Hide 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. 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.

Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 66 128 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
26.1 [1] 
(NA to NA)
23.3
(12.2 to 29.6)
24.0 [1] 
(NA to NA)
NA [2] 
(NA to NA)
[1]
N/A = Both lower and upper confidence intervals were not estimable as limited numbers of PD or death were observed.
[2]
NA = Median DoR was non-estimable for patients with mBCC receiving treatment with sonidegib 800 mg as limited numbers of PD or death were observed.
5.Secondary Outcome
Title Complete Response Rate (CRR) Per Central Review (pEAS)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
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)
6.Secondary Outcome
Title Complete Response Rate (CRR) Per Central Review (FAS)
Hide 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
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 66 128 13 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
3.0
(0.4 to 10.5)
0.0
(0.0 to 2.8)
0.0
(0.0 to 24.7)
0.0
(0.0 to 14.8)
7.Secondary Outcome
Title Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
19.0 [1] 
(NA to NA)
19.4
(13.8 to 30.5)
13.1
(5.6 to 33.1)
11.1
(7.3 to 16.6)
[1]
N/A = Both lower and upper confidence intervals were not estimable as limited numbers of PD or death were observed.
8.Secondary Outcome
Title Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients).
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 66 128 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
22.1 [1] 
(NA to NA)
24.9
(19.2 to 33.4)
13.1
(5.6 to 33.1)
11.1
(7.3 to 16.6)
[1]
N/A = Both lower and upper confidence intervals were not estimable as limited numbers of PD or death were observed.
9.Secondary Outcome
Title Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
4.0
(3.7 to 5.6)
3.7
(2.0 to 5.5)
9.2 [1] 
(NA to NA)
1.0
(1.0 to 2.1)
[1]
N/A = Both lower and upper confidence intervals were not estimable as limited numbers of PD or death were observed.
10.Secondary Outcome
Title Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients).
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
4.0
(3.7 to 5.6)
3.7
(2.0 to 5.5)
9.2 [1] 
(NA to NA)
1.0
(1.0 to 2.1)
[1]
N/A = Both lower and upper confidence intervals were not estimable as limited numbers of PD or death were observed.
11.Secondary Outcome
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)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
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)
12.Secondary Outcome
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)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients).
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 66 128 13 23
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
71.2
(58.7 to 81.7)
58.6
(49.6 to 67.2)
23.1
(5.0 to 53.8)
34.8
(16.4 to 57.3)
13.Secondary Outcome
Title Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Hide 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.

Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
18.2
(12.9 to 23.0)
26.0
(15.7 to 47.3)
18.1
(17.7 to 18.4)
10.2 [1] 
(NA to NA)
[1]
N/A = Both lower and upper confidence intervals were not estimable as limited numbers of PD or death were observed.
14.Secondary Outcome
Title Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 66 128 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
15.7
(12.0 to 20.2)
26.0
(18.3 to 47.3)
18.1
(17.7 to 18.4)
10.2 [1] 
(NA to NA)
[1]
N/A = Both lower and upper confidence intervals were not estimable as limited numbers of PD or death were observed.
15.Secondary Outcome
Title Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
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)
16.Secondary Outcome
Title Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
Hide 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis set (pEAS) was a subset of the full analysis set (FAS) including patients with laBCC with tumors that were adequately assessed by MRI or photography or both, & including all patients with mBCC included in the FAS which comprised all patients who were assigned study treatment irrespective of receiving it.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 42 93 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
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)
17.Secondary Outcome
Title Plasma Concentration of Sonidegib (LDE225)
Hide 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.
Time Frame Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set (PAS) consisted of all patients with at least one evaluable plasma concentration.
Arm/Group Title LDE225 200 mg qd LDE225 800 mg qd
Hide Arm/Group 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.
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.
Overall Number of Participants Analyzed 73 139
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Week 1 (0 h (pre-dose)) Number Analyzed 73 participants 139 participants
NA [1] 
(NA%)
NA [1] 
(NA%)
Week 3 (0 h (pre-dose)) Number Analyzed 65 participants 128 participants
207.76
(78.29%)
586.76
(97.13%)
Week 5 (0 h (pre-dose)) Number Analyzed 70 participants 120 participants
372.26
(68.89%)
1012.63
(70.42%)
Week 9 (0 h (pre-dose)) Number Analyzed 68 participants 101 participants
559.29
(67.30%)
1353.06
(63.43%)
Week 13 (0 h (pre-dose)) Number Analyzed 63 participants 85 participants
714.01
(60.79%)
1443.84
(61.57%)
Week 17 (0 h (pre-dose)) Number Analyzed 66 participants 81 participants
688.93
(64.43%)
1574.21
(59.88%)
Week 17 (1 h (post-dose)) Number Analyzed 35 participants 35 participants
841.78
(52.57%)
1803.74
(39.47%)
Week 17 (2 h (post-dose)) Number Analyzed 37 participants 32 participants
939.56
(50.79%)
1922.38
(34.90%)
Week 17 (4 h (post-dose)) Number Analyzed 36 participants 33 participants
842.31
(62.22%)
1750.70
(53.32%)
Week 17 (6 h (post-dose)) Number Analyzed 33 participants 32 participants
759.88
(63.43%)
1673.95
(41.53%)
Week 21 (0 h (pre-dose)) Number Analyzed 58 participants 67 participants
707.49
(63.58%)
1547.41
(63.92%)
Week 33 (0 h (pre-dose)) Number Analyzed 49 participants 49 participants
702.67
(93.11%)
1477.60
(74.80%)
Week 45 (0 h (pre-dose)) Number Analyzed 33 participants 35 participants
697.92
(76.02%)
1368.87
(79.60%)
Week 57 (0 h (pre-dose)) Number Analyzed 22 participants 26 participants
559.17
(117.27%)
1257.42
(78.96%)
Wek 69 (0 h (pre-dose)) Number Analyzed 21 participants 23 participants
530.91
(154.33%)
1355.91
(89.03%)
[1]
N/A = Week1 pre-dose concentrations were below limit of quantitation
18.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time from date of randomization to 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.
Time Frame 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) comprised all patients who were assigned study treatment irrespective of receiving it (all randomized patients). Patients were classified according to the treatment they were assigned in accordance with the intention-to-treat (ITT) principle.
Arm/Group Title LDE225 200mg laBCC LDE225 800mg laBCC LDE225 200mg mBCC LDE225 800mg mBCC
Hide Arm/Group 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.
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.
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.
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.
Overall Number of Participants Analyzed 66 128 13 23
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [2] 
(NA to NA)
47.6 [3] 
(NA to NA)
33.8 [3] 
(NA to NA)
[1]
N/A = Median OS was non-estimable for patients with laBCC receiving treatment with sonidegib 200 mg as limited number of deaths were observed.
[2]
N/A = Median OS was non-estimable for patients with laBCC receiving treatment with sonidegib 800 mg as limited number of deaths were observed.
[3]
N/A = Both lower and upper confidence intervals were not estimable as limited number of deaths were observed.
Time Frame 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 Description All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 7 years.
 
Arm/Group Title LDE225 200 mg qd LDE225 800 mg qd
Hide Arm/Group 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. 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.
All-Cause Mortality
LDE225 200 mg qd LDE225 800 mg qd
Affected / at Risk (%) Affected / at Risk (%)
Total   1/79 (1.27%)   7/150 (4.67%) 
Hide Serious Adverse Events
LDE225 200 mg qd LDE225 800 mg qd
Affected / at Risk (%) Affected / at Risk (%)
Total   16/79 (20.25%)   58/150 (38.67%) 
Blood and lymphatic system disorders     
Anaemia  1  0/79 (0.00%)  5/150 (3.33%) 
Cardiac disorders     
Angina pectoris  1  1/79 (1.27%)  1/150 (0.67%) 
Atrial fibrillation  1  0/79 (0.00%)  1/150 (0.67%) 
Bradycardia  1  0/79 (0.00%)  1/150 (0.67%) 
Bundle branch block left  1  0/79 (0.00%)  1/150 (0.67%) 
Cardiac arrest  1  0/79 (0.00%)  1/150 (0.67%) 
Cardiac failure congestive  1  0/79 (0.00%)  1/150 (0.67%) 
Cardiovascular insufficiency  1  0/79 (0.00%)  1/150 (0.67%) 
Sinus tachycardia  1  0/79 (0.00%)  1/150 (0.67%) 
Gastrointestinal disorders     
Chronic gastritis  1  0/79 (0.00%)  1/150 (0.67%) 
Constipation  1  0/79 (0.00%)  1/150 (0.67%) 
Diarrhoea  1  0/79 (0.00%)  2/150 (1.33%) 
Duodenal stenosis  1  0/79 (0.00%)  1/150 (0.67%) 
Duodenal ulcer  1  0/79 (0.00%)  1/150 (0.67%) 
Gastric ulcer  1  1/79 (1.27%)  0/150 (0.00%) 
Gastritis  1  0/79 (0.00%)  1/150 (0.67%) 
Gastritis erosive  1  0/79 (0.00%)  1/150 (0.67%) 
Gastrointestinal pain  1  0/79 (0.00%)  1/150 (0.67%) 
Nausea  1  0/79 (0.00%)  3/150 (2.00%) 
Pancreatitis acute  1  0/79 (0.00%)  1/150 (0.67%) 
Peptic ulcer perforation  1  0/79 (0.00%)  1/150 (0.67%) 
Small intestinal obstruction  1  0/79 (0.00%)  2/150 (1.33%) 
Upper gastrointestinal haemorrhage  1  0/79 (0.00%)  1/150 (0.67%) 
Vomiting  1  0/79 (0.00%)  4/150 (2.67%) 
General disorders     
Cardiac death  1  0/79 (0.00%)  1/150 (0.67%) 
Facial pain  1  1/79 (1.27%)  0/150 (0.00%) 
General physical health deterioration  1  1/79 (1.27%)  1/150 (0.67%) 
Non-cardiac chest pain  1  0/79 (0.00%)  1/150 (0.67%) 
Pain  1  0/79 (0.00%)  1/150 (0.67%) 
Hepatobiliary disorders     
Cholelithiasis  1  0/79 (0.00%)  1/150 (0.67%) 
Hepatotoxicity  1  0/79 (0.00%)  1/150 (0.67%) 
Infections and infestations     
Abscess  1  0/79 (0.00%)  1/150 (0.67%) 
Abscess limb  1  0/79 (0.00%)  2/150 (1.33%) 
Bronchitis  1  1/79 (1.27%)  0/150 (0.00%) 
Cellulitis  1  1/79 (1.27%)  1/150 (0.67%) 
Endocarditis  1  1/79 (1.27%)  0/150 (0.00%) 
Escherichia urinary tract infection  1  1/79 (1.27%)  0/150 (0.00%) 
Lower respiratory tract infection  1  1/79 (1.27%)  0/150 (0.00%) 
Mastoiditis  1  0/79 (0.00%)  1/150 (0.67%) 
Otitis media  1  0/79 (0.00%)  1/150 (0.67%) 
Parotitis  1  0/79 (0.00%)  1/150 (0.67%) 
Pneumonia  1  2/79 (2.53%)  3/150 (2.00%) 
Pseudomonas infection  1  0/79 (0.00%)  1/150 (0.67%) 
Sepsis  1  1/79 (1.27%)  1/150 (0.67%) 
Septic shock  1  1/79 (1.27%)  0/150 (0.00%) 
Superinfection  1  0/79 (0.00%)  1/150 (0.67%) 
Urinary tract infection  1  1/79 (1.27%)  2/150 (1.33%) 
Injury, poisoning and procedural complications     
Arthropod bite  1  0/79 (0.00%)  1/150 (0.67%) 
Cervical vertebral fracture  1  1/79 (1.27%)  1/150 (0.67%) 
Fall  1  1/79 (1.27%)  0/150 (0.00%) 
Femoral neck fracture  1  1/79 (1.27%)  0/150 (0.00%) 
Joint dislocation  1  1/79 (1.27%)  0/150 (0.00%) 
Lumbar vertebral fracture  1  1/79 (1.27%)  0/150 (0.00%) 
Spinal fracture  1  0/79 (0.00%)  1/150 (0.67%) 
Upper limb fracture  1  1/79 (1.27%)  1/150 (0.67%) 
Investigations     
Blood creatine phosphokinase MB increased  1  1/79 (1.27%)  0/150 (0.00%) 
Blood creatine phosphokinase increased  1  1/79 (1.27%)  6/150 (4.00%) 
Lipase increased  1  0/79 (0.00%)  1/150 (0.67%) 
Myoglobin blood increased  1  0/79 (0.00%)  1/150 (0.67%) 
Weight decreased  1  0/79 (0.00%)  1/150 (0.67%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/79 (0.00%)  2/150 (1.33%) 
Dehydration  1  1/79 (1.27%)  3/150 (2.00%) 
Failure to thrive  1  0/79 (0.00%)  1/150 (0.67%) 
Hypoglycaemia  1  1/79 (1.27%)  0/150 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscle contracture  1  0/79 (0.00%)  1/150 (0.67%) 
Muscular weakness  1  0/79 (0.00%)  1/150 (0.67%) 
Myositis  1  0/79 (0.00%)  1/150 (0.67%) 
Osteonecrosis of jaw  1  0/79 (0.00%)  1/150 (0.67%) 
Rhabdomyolysis  1  1/79 (1.27%)  5/150 (3.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
B-cell lymphoma  1  0/79 (0.00%)  1/150 (0.67%) 
Basal cell carcinoma  1  0/79 (0.00%)  2/150 (1.33%) 
Brain neoplasm  1  0/79 (0.00%)  1/150 (0.67%) 
Invasive papillary breast carcinoma  1  1/79 (1.27%)  0/150 (0.00%) 
Lung neoplasm  1  0/79 (0.00%)  1/150 (0.67%) 
Malignant melanoma  1  0/79 (0.00%)  1/150 (0.67%) 
Prostate cancer  1  0/79 (0.00%)  1/150 (0.67%) 
Squamous cell carcinoma  1  0/79 (0.00%)  1/150 (0.67%) 
Transitional cell carcinoma  1  0/79 (0.00%)  1/150 (0.67%) 
Nervous system disorders     
Cerebrovascular accident  1  1/79 (1.27%)  0/150 (0.00%) 
Dysgeusia  1  0/79 (0.00%)  1/150 (0.67%) 
Haemorrhage intracranial  1  1/79 (1.27%)  0/150 (0.00%) 
Paraesthesia  1  0/79 (0.00%)  1/150 (0.67%) 
Somnolence  1  0/79 (0.00%)  1/150 (0.67%) 
Syncope  1  1/79 (1.27%)  2/150 (1.33%) 
Psychiatric disorders     
Bipolar disorder  1  1/79 (1.27%)  0/150 (0.00%) 
Mental status changes  1  0/79 (0.00%)  1/150 (0.67%) 
Renal and urinary disorders     
Acute kidney injury  1  1/79 (1.27%)  0/150 (0.00%) 
Bladder obstruction  1  0/79 (0.00%)  1/150 (0.67%) 
Haematuria  1  0/79 (0.00%)  1/150 (0.67%) 
Nephropathy toxic  1  0/79 (0.00%)  1/150 (0.67%) 
Reproductive system and breast disorders     
Uterine prolapse  1  0/79 (0.00%)  1/150 (0.67%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/79 (1.27%)  0/150 (0.00%) 
Bronchitis chronic  1  0/79 (0.00%)  1/150 (0.67%) 
Dyspnoea  1  1/79 (1.27%)  2/150 (1.33%) 
Emphysema  1  0/79 (0.00%)  1/150 (0.67%) 
Pleural effusion  1  1/79 (1.27%)  0/150 (0.00%) 
Respiratory arrest  1  0/79 (0.00%)  1/150 (0.67%) 
Rhinorrhoea  1  0/79 (0.00%)  1/150 (0.67%) 
Sputum discoloured  1  0/79 (0.00%)  1/150 (0.67%) 
Skin and subcutaneous tissue disorders     
Skin lesion  1  0/79 (0.00%)  1/150 (0.67%) 
Vascular disorders     
Arterial haemorrhage  1  0/79 (0.00%)  1/150 (0.67%) 
Deep vein thrombosis  1  0/79 (0.00%)  2/150 (1.33%) 
Hypotension  1  1/79 (1.27%)  1/150 (0.67%) 
Orthostatic hypotension  1  1/79 (1.27%)  0/150 (0.00%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LDE225 200 mg qd LDE225 800 mg qd
Affected / at Risk (%) Affected / at Risk (%)
Total   76/79 (96.20%)   145/150 (96.67%) 
Blood and lymphatic system disorders     
Anaemia  1  4/79 (5.06%)  13/150 (8.67%) 
Ear and labyrinth disorders     
Vertigo  1  0/79 (0.00%)  11/150 (7.33%) 
Gastrointestinal disorders     
Abdominal pain  1  8/79 (10.13%)  9/150 (6.00%) 
Abdominal pain upper  1  7/79 (8.86%)  12/150 (8.00%) 
Constipation  1  6/79 (7.59%)  24/150 (16.00%) 
Diarrhoea  1  25/79 (31.65%)  34/150 (22.67%) 
Dry mouth  1  4/79 (5.06%)  8/150 (5.33%) 
Nausea  1  31/79 (39.24%)  71/150 (47.33%) 
Vomiting  1  9/79 (11.39%)  41/150 (27.33%) 
General disorders     
Asthenia  1  10/79 (12.66%)  9/150 (6.00%) 
Fatigue  1  26/79 (32.91%)  55/150 (36.67%) 
Pyrexia  1  4/79 (5.06%)  5/150 (3.33%) 
Infections and infestations     
Influenza  1  4/79 (5.06%)  8/150 (5.33%) 
Nasopharyngitis  1  8/79 (10.13%)  17/150 (11.33%) 
Pneumonia  1  4/79 (5.06%)  3/150 (2.00%) 
Upper respiratory tract infection  1  5/79 (6.33%)  11/150 (7.33%) 
Urinary tract infection  1  7/79 (8.86%)  7/150 (4.67%) 
Injury, poisoning and procedural complications     
Fall  1  5/79 (6.33%)  5/150 (3.33%) 
Investigations     
Blood creatine phosphokinase increased  1  23/79 (29.11%)  54/150 (36.00%) 
Lipase increased  1  6/79 (7.59%)  13/150 (8.67%) 
Weight decreased  1  24/79 (30.38%)  64/150 (42.67%) 
Metabolism and nutrition disorders     
Decreased appetite  1  18/79 (22.78%)  52/150 (34.67%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  13/79 (16.46%)  17/150 (11.33%) 
Back pain  1  6/79 (7.59%)  16/150 (10.67%) 
Muscle spasms  1  43/79 (54.43%)  104/150 (69.33%) 
Muscular weakness  1  4/79 (5.06%)  8/150 (5.33%) 
Musculoskeletal pain  1  4/79 (5.06%)  7/150 (4.67%) 
Myalgia  1  15/79 (18.99%)  42/150 (28.00%) 
Pain in extremity  1  5/79 (6.33%)  8/150 (5.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Squamous cell carcinoma  1  4/79 (5.06%)  5/150 (3.33%) 
Nervous system disorders     
Ageusia  1  1/79 (1.27%)  15/150 (10.00%) 
Dizziness  1  7/79 (8.86%)  15/150 (10.00%) 
Dysgeusia  1  35/79 (44.30%)  89/150 (59.33%) 
Headache  1  12/79 (15.19%)  20/150 (13.33%) 
Hypogeusia  1  0/79 (0.00%)  9/150 (6.00%) 
Paraesthesia  1  4/79 (5.06%)  6/150 (4.00%) 
Psychiatric disorders     
Depression  1  5/79 (6.33%)  9/150 (6.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  7/79 (8.86%)  11/150 (7.33%) 
Oropharyngeal pain  1  4/79 (5.06%)  6/150 (4.00%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  39/79 (49.37%)  87/150 (58.00%) 
Pruritus  1  6/79 (7.59%)  12/150 (8.00%) 
Vascular disorders     
Hypertension  1  8/79 (10.13%)  16/150 (10.67%) 
1
Term from vocabulary, MedDRA (19.1)
Indicates events were collected by systematic assessment
230 patients evaluated in the Full Analysis Set: 79 randomized to LDE225 (Sonidegib) 200mg group & 151 randomized to LDE225 800mg group. 1 patient randomized to the 800mg group did not receive study treatment & thus was not counted in the Safety Set.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01327053    
Other Study ID Numbers: CLDE225A2201
2010-022629-14 ( EudraCT Number )
First Submitted: March 30, 2011
First Posted: April 1, 2011
Results First Submitted: August 24, 2015
Results First Posted: November 23, 2015
Last Update Posted: August 28, 2019