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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01327053
• Collaborator: (none)
• Enrollment: 230
• Locations: 62
• Arms: 2
• Actual Duration (Months): 84
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study assessed the efficacy and safety of oral treatment with two dose levels of LDE225 in patients with locally advanced or metastatic BCC.

Condition or Disease	Intervention/Treatment	Phase
Basal Cell Carcinoma	Drug: LDE225	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 230 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jun 29, 2011
• Actual Primary Completion Date: Jun 28, 2013
• Actual Study Completion Date: Jun 29, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDE225 200 mg The study was double blinded and enrolled at least 50 evaluable patients in the 200 mg LDE225 arm. The efficacy and safety of LDE225 was 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.	Drug: LDE225; LDE225 was administered orally, on a continuous once daily dosing schedule and was supplied as 200 mg hard gelatin capsules in bottles. Every 4 weeks on the day of study visit, patients received a prescription of an adequate drug supply for self-administration at home. The 800 mg dose patients received 4 capsules of LDE225 and 200 mg dose arm patients received 1 LDE225 capsule + 3 placebo capsules.; Other Names: Sonidegib
Experimental: LDE225 800 mg The study was double blinded and enrolled at least 100 evaluable patients in the 800 mg LDE225 arm. The efficacy and safety of LDE225 was 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.	Drug: LDE225; LDE225 was administered orally, on a continuous once daily dosing schedule and was supplied as 200 mg hard gelatin capsules in bottles. Every 4 weeks on the day of study visit, patients received a prescription of an adequate drug supply for self-administration at home. The 800 mg dose patients received 4 capsules of LDE225 and 200 mg dose arm patients received 1 LDE225 capsule + 3 placebo capsules.; Other Names: Sonidegib

Outcome Measures

Primary Outcome Measures

1. 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) [6 months]

   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.

2. 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) [6 months]

   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.

Secondary Outcome Measures

1. Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) [42 months]

   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.

2. Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) [42 months]

   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.

3. Complete Response Rate (CRR) Per Central Review (pEAS) [42 months]

   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.

4. Complete Response Rate (CRR) Per Central Review (FAS) [6 months]

   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

5. Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) [42 months]

   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.

6. Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) [42 months]

   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.

7. Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) [42 months]

   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.

8. Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) [42 months]

   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.

9. 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) [42 months]

   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.

10. 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) [42 months]

    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.

11. Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) [42 months]

    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.

12. Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS) [42 months]

    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.

13. Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) [42 months]

    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.

14. Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS) [42 months]

    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.

15. Plasma Concentration of Sonidegib (LDE225) [Weeks 1, 3, 5, 9, 13, 17, 21, 33, 45, 57, 69]

    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.

16. Overall Survival (OS) [42 months]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with locally advanced BCC and metastatic BCC

• Patients with adequate bone marrow, liver, and renal function

Exclusion Criteria:

• Patients who had had major surgery within 4 weeks of initiation of study medication

• Patients unable to take oral drugs or with lack of physical integrity of the upper gastrointestinal tract, or known malabsorption syndromes.

• Patients with concurrent medical conditions that may interfere or potentially affect the interpretation of the study.

• Patients with neuromuscular disorders or are on concurrent treatment with drugs that may cause muscle damage.

• Patients who were on concurrent therapy with other anti-neoplastic agents.

• Patients who had taken part in an experimental drug within 4 weeks of initiation of study medication.

• Pregnant or nursing (lactating) women

• Women of child bearing potential unwilling to use 2 forms of highly effective contraception throughout the study and for 3 months after the last treatment

• Fertile males not willing to use condoms throughout the study and for 3 months after the last treatment.

• Patients who were unwilling or unable to comply with the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	University of California at Los Angeles UCLA 3	Los Angeles	California	United States	90095
3	Stanford University Medical Center Stanford Univ 2	Stanford	California	United States	94304
4	University of Colorado School of Medicine UC	Aurora	Colorado	United States	80045
5	Washington Hospital Center Wash Hospital	Washington	District of Columbia	United States	20010
6	H Lee Moffitt Cancer Center and Research Institute Cutaneous Onc Dept	Tampa	Florida	United States	33612
7	NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Study coordinator	Chicago	Illinois	United States	60611
8	Dana Farber Cancer Institute DFCI - MA	Boston	Massachusetts	United States	02215
9	Henry Ford Hospital Henry Ford	Detroit	Michigan	United States	48202 2689
10	Washington University School Of Medicine-Siteman Cancer Ctr Siteman	Saint Louis	Missouri	United States	63110
11	Comprehensive Cancer Centers of Nevada CCC of Nevada- Southwest (2)	Las Vegas	Nevada	United States	89109
12	Hackensack University Medical Center Hackensack (SC)	Hackensack	New Jersey	United States	07601
13	New York University Medical Center SC-2	New York	New York	United States	10016
14	Penn State University / Milton S. Hershey Medical Center Hershey Medical	Hershey	Pennsylvania	United States	17033-085
15	University of Pittsburgh Medical Center UPMC	Pittsburgh	Pennsylvania	United States	15213
16	Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology	Dallas	Texas	United States	75246
17	Texas Oncology Tex Onc 3	Dallas	Texas	United States	75246
18	Texas Oncology Texas Onc - Amarillo	Dallas	Texas	United States	75246
19	University of Texas MD Anderson Cancer Center MD Anderson	Houston	Texas	United States	77030
20	Texas Oncology Cancer Care & Research Center	Waco	Texas	United States	76712
21	Texoma Cancer Center Texoma Cancer Center	Wichita Falls	Texas	United States	76310
22	University of Utah / Huntsman Cancer Institute Huntsman/Univ UT	Salt Lake City	Utah	United States	84103
23	Novartis Investigative Site	St Leonards	New South Wales	Australia	2065
24	Novartis Investigative Site	Geelong	Victoria	Australia	3220
25	Novartis Investigative Site	Bruxelles		Belgium	1200
26	Novartis Investigative Site	Wilrijk		Belgium	2610
27	Novartis Investigative Site	Waterloo	Ontario	Canada	N2J 1C4
28	Novartis Investigative Site	Sainte-Foy	Quebec	Canada	G1V 4T3
29	Novartis Investigative Site	Lyon Cedex		France	69373
30	Novartis Investigative Site	Marseille Cedex 05		France	13885
31	Novartis Investigative Site	Pierre Benite Cedex		France	69495
32	Novartis Investigative Site	Toulouse Cedex 9		France	31059
33	Novartis Investigative Site	Villejuif Cedex		France	94805
34	Novartis Investigative Site	Berlin		Germany	13353
35	Novartis Investigative Site	Essen		Germany	45147
36	Novartis Investigative Site	Freiburg		Germany	79106
37	Novartis Investigative Site	Gera		Germany	07548
38	Novartis Investigative Site	Hannover		Germany	30625
39	Novartis Investigative Site	Kiel		Germany	24105
40	Novartis Investigative Site	Mainz		Germany	55131
41	Novartis Investigative Site	Muenchen		Germany	81377
42	Novartis Investigative Site	Muenster		Germany	48157
43	Novartis Investigative Site	Stade		Germany	21682
44	Novartis Investigative Site	Athens		Greece	161 21
45	Novartis Investigative Site	Budapest		Hungary	H-1085
46	Novartis Investigative Site	Debrecen		Hungary	4032
47	Novartis Investigative Site	Szeged		Hungary	H-6725
48	Novartis Investigative Site	Torino	TO	Italy	10126
49	Novartis Investigative Site	Napoli		Italy	80131
50	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
51	Novartis Investigative Site	Madrid		Spain	28034
52	Novartis Investigative Site	Madrid		Spain	28046
53	Novartis Investigative Site	Bern		Switzerland	3010
54	Novartis Investigative Site	Geneve		Switzerland	1211
55	Novartis Investigative Site	Zürich		Switzerland	8091
56	Novartis Investigative Site	High Heaton	Newcastle Upon Tyne	United Kingdom	NE7 7DN
57	Novartis Investigative Site	Yeovil	Somerset	United Kingdom	BA21 4AT
58	Novartis Investigative Site	Cardiff		United Kingdom	CF14 4XW
59	Novartis Investigative Site	Glasgow		United Kingdom	G3 8SJ
60	Novartis Investigative Site	Leicester		United Kingdom	LE1 5WW
61	Novartis Investigative Site	London		United Kingdom	EC1A 7BE
62	Novartis Investigative Site	Manchester		United Kingdom	M13 9WL

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01327053
• Other Study ID Numbers: CLDE225A2201; 2010-022629-14
• First Posted: Apr 1, 2011
• Last Update Posted: Aug 28, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: locally advanced basal cell carcinoma; metastatic basal cell carcinoma; LDE225; sonidegib; Basel Cell Carcinoma (BCC); skin cancer; Basel Cell Carcinoma; BCC
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Basal Cell

Study Results

Participant Flow

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 Detail	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
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
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

Baseline Characteristics

Arm/Group Title	LDE225 (Sonidegib) 200 mg	LDE225 (Sonidegib) 800 mg	Total
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 Participants	79	151	230
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.6 (15.67)	63.6 (14.59)	64.3 (14.96)
Sex: Female, Male (Count of Participants)
Female	31 39.2%	55 36.4%	86 37.4%
Male	48 60.8%	96 63.6%	144 62.6%
Race/Ethnicity, Customized (Number) [Number]
Black	0 0%	1 0.7%	1 0.4%
Caucasian	71 89.9%	145 96%	216 93.9%
Other	8 10.1%	5 3.3%	13 5.7%

Outcome Measures

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)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Number (95% Confidence Interval) [Percentage of participants]	42.9 54.3%	37.6 24.9%	15.4 6.7%	17.4 NaN

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)
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

Outcome Measure Data

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
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.
Measure Participants	66	128	13	23
Number (95% Confidence Interval) [Percentage of participants]	47.0 59.5%	35.2 23.3%	15.4 6.7%	17.4 NaN

3. Secondary Outcome

Title	Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Median (95% Confidence Interval) [Months]	12.9	23.7	24.0	NA

4. Secondary Outcome

Title	Duration of Response (DoR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
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

Outcome Measure Data

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
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.
Measure Participants	66	128	13	23
Median (95% Confidence Interval) [Months]	26.1	23.3	24.0	NA

5. Secondary Outcome

Title	Complete Response Rate (CRR) Per Central Review (pEAS)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Number (95% Confidence Interval) [Percentage of participants]	4.8 6.1%	2.2 1.5%	0.0 0%	0.0 NaN

6. Secondary Outcome

Title	Complete Response Rate (CRR) Per Central Review (FAS)
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

Outcome Measure Data

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
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.
Measure Participants	66	128	13	23
Number (95% Confidence Interval) [Percentage of participants]	3.0 3.8%	0.0 0%	0.0 0%	0.0 NaN

7. Secondary Outcome

Title	Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Median (95% Confidence Interval) [Months]	19.0	19.4	13.1	11.1

8. Secondary Outcome

Title	Progression-free Survival (PFS) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
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

Outcome Measure Data

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
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.
Measure Participants	66	128	13	23
Median (95% Confidence Interval) [Months]	22.1	24.9	13.1	11.1

9. Secondary Outcome

Title	Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Median (95% Confidence Interval) [Months]	4.0	3.7	9.2	1.0

10. Secondary Outcome

Title	Time to Tumor Response (TTR) Per Central Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Median (95% Confidence Interval) [Months]	4.0	3.7	9.2	1.0

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)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Number (95% Confidence Interval) [Percentage of participants]	71.4 90.4%	61.3 40.6%	23.1 10%	34.8 NaN

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)
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

Outcome Measure Data

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
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.
Measure Participants	66	128	13	23
Number (95% Confidence Interval) [Percentage of participants]	71.2 90.1%	58.6 38.8%	23.1 10%	34.8 NaN

13. Secondary Outcome

Title	Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Median (95% Confidence Interval) [Months]	18.2	26.0	18.1	10.2

14. Secondary Outcome

Title	Duration of Response (DoR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (FAS)
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

Outcome Measure Data

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
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.
Measure Participants	66	128	13	23
Median (95% Confidence Interval) [Months]	15.7	26.0	18.1	10.2

15. Secondary Outcome

Title	Progression-free Survival (PFS) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Median (95% Confidence Interval) [Months]	20.1	28.0	13.1	14.3

16. Secondary Outcome

Title	Time to Tumor Response (TTR) Per Site Investigator Review Using mRECIST for laBCC and RECIST 1.1 for mBCC (pEAS)
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

Outcome Measure Data

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
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.
Measure Participants	42	93	13	23
Median (95% Confidence Interval) [Months]	1.9	1.8	1.0	2.7

17. Secondary Outcome

Title	Plasma Concentration of Sonidegib (LDE225)
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

Outcome Measure Data

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
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.
Measure Participants	73	139
Week 1 (0 h (pre-dose))	NA (NA)	NA (NA)
Week 3 (0 h (pre-dose))	207.76 (78.29)	586.76 (97.13)
Week 5 (0 h (pre-dose))	372.26 (68.89)	1012.63 (70.42)
Week 9 (0 h (pre-dose))	559.29 (67.30)	1353.06 (63.43)
Week 13 (0 h (pre-dose))	714.01 (60.79)	1443.84 (61.57)
Week 17 (0 h (pre-dose))	688.93 (64.43)	1574.21 (59.88)
Week 17 (1 h (post-dose))	841.78 (52.57)	1803.74 (39.47)
Week 17 (2 h (post-dose))	939.56 (50.79)	1922.38 (34.90)
Week 17 (4 h (post-dose))	842.31 (62.22)	1750.70 (53.32)
Week 17 (6 h (post-dose))	759.88 (63.43)	1673.95 (41.53)
Week 21 (0 h (pre-dose))	707.49 (63.58)	1547.41 (63.92)
Week 33 (0 h (pre-dose))	702.67 (93.11)	1477.60 (74.80)
Week 45 (0 h (pre-dose))	697.92 (76.02)	1368.87 (79.60)
Week 57 (0 h (pre-dose))	559.17 (117.27)	1257.42 (78.96)
Wek 69 (0 h (pre-dose))	530.91 (154.33)	1355.91 (89.03)

18. Secondary Outcome

Title	Overall Survival (OS)
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

Outcome Measure Data

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
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.
Measure Participants	66	128	13	23
Median (95% Confidence Interval) [Months]	NA	NA	47.6	33.8

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	1/79 (1.3%)		7/150 (4.7%)
Serious Adverse Events
	LDE225 200 mg qd		LDE225 800 mg qd
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/79 (20.3%)		58/150 (38.7%)
Blood and lymphatic system disorders
Anaemia	0/79 (0%)		5/150 (3.3%)
Cardiac disorders
Angina pectoris	1/79 (1.3%)		1/150 (0.7%)
Atrial fibrillation	0/79 (0%)		1/150 (0.7%)
Bradycardia	0/79 (0%)		1/150 (0.7%)
Bundle branch block left	0/79 (0%)		1/150 (0.7%)
Cardiac arrest	0/79 (0%)		1/150 (0.7%)
Cardiac failure congestive	0/79 (0%)		1/150 (0.7%)
Cardiovascular insufficiency	0/79 (0%)		1/150 (0.7%)
Sinus tachycardia	0/79 (0%)		1/150 (0.7%)
Gastrointestinal disorders
Chronic gastritis	0/79 (0%)		1/150 (0.7%)
Constipation	0/79 (0%)		1/150 (0.7%)
Diarrhoea	0/79 (0%)		2/150 (1.3%)
Duodenal stenosis	0/79 (0%)		1/150 (0.7%)
Duodenal ulcer	0/79 (0%)		1/150 (0.7%)
Gastric ulcer	1/79 (1.3%)		0/150 (0%)
Gastritis	0/79 (0%)		1/150 (0.7%)
Gastritis erosive	0/79 (0%)		1/150 (0.7%)
Gastrointestinal pain	0/79 (0%)		1/150 (0.7%)
Nausea	0/79 (0%)		3/150 (2%)
Pancreatitis acute	0/79 (0%)		1/150 (0.7%)
Peptic ulcer perforation	0/79 (0%)		1/150 (0.7%)
Small intestinal obstruction	0/79 (0%)		2/150 (1.3%)
Upper gastrointestinal haemorrhage	0/79 (0%)		1/150 (0.7%)
Vomiting	0/79 (0%)		4/150 (2.7%)
General disorders
Cardiac death	0/79 (0%)		1/150 (0.7%)
Facial pain	1/79 (1.3%)		0/150 (0%)
General physical health deterioration	1/79 (1.3%)		1/150 (0.7%)
Non-cardiac chest pain	0/79 (0%)		1/150 (0.7%)
Pain	0/79 (0%)		1/150 (0.7%)
Hepatobiliary disorders
Cholelithiasis	0/79 (0%)		1/150 (0.7%)
Hepatotoxicity	0/79 (0%)		1/150 (0.7%)
Infections and infestations
Abscess	0/79 (0%)		1/150 (0.7%)
Abscess limb	0/79 (0%)		2/150 (1.3%)
Bronchitis	1/79 (1.3%)		0/150 (0%)
Cellulitis	1/79 (1.3%)		1/150 (0.7%)
Endocarditis	1/79 (1.3%)		0/150 (0%)
Escherichia urinary tract infection	1/79 (1.3%)		0/150 (0%)
Lower respiratory tract infection	1/79 (1.3%)		0/150 (0%)
Mastoiditis	0/79 (0%)		1/150 (0.7%)
Otitis media	0/79 (0%)		1/150 (0.7%)
Parotitis	0/79 (0%)		1/150 (0.7%)
Pneumonia	2/79 (2.5%)		3/150 (2%)
Pseudomonas infection	0/79 (0%)		1/150 (0.7%)
Sepsis	1/79 (1.3%)		1/150 (0.7%)
Septic shock	1/79 (1.3%)		0/150 (0%)
Superinfection	0/79 (0%)		1/150 (0.7%)
Urinary tract infection	1/79 (1.3%)		2/150 (1.3%)
Injury, poisoning and procedural complications
Arthropod bite	0/79 (0%)		1/150 (0.7%)
Cervical vertebral fracture	1/79 (1.3%)		1/150 (0.7%)
Fall	1/79 (1.3%)		0/150 (0%)
Femoral neck fracture	1/79 (1.3%)		0/150 (0%)
Joint dislocation	1/79 (1.3%)		0/150 (0%)
Lumbar vertebral fracture	1/79 (1.3%)		0/150 (0%)
Spinal fracture	0/79 (0%)		1/150 (0.7%)
Upper limb fracture	1/79 (1.3%)		1/150 (0.7%)
Investigations
Blood creatine phosphokinase MB increased	1/79 (1.3%)		0/150 (0%)
Blood creatine phosphokinase increased	1/79 (1.3%)		6/150 (4%)
Lipase increased	0/79 (0%)		1/150 (0.7%)
Myoglobin blood increased	0/79 (0%)		1/150 (0.7%)
Weight decreased	0/79 (0%)		1/150 (0.7%)
Metabolism and nutrition disorders
Decreased appetite	0/79 (0%)		2/150 (1.3%)
Dehydration	1/79 (1.3%)		3/150 (2%)
Failure to thrive	0/79 (0%)		1/150 (0.7%)
Hypoglycaemia	1/79 (1.3%)		0/150 (0%)
Musculoskeletal and connective tissue disorders
Muscle contracture	0/79 (0%)		1/150 (0.7%)
Muscular weakness	0/79 (0%)		1/150 (0.7%)
Myositis	0/79 (0%)		1/150 (0.7%)
Osteonecrosis of jaw	0/79 (0%)		1/150 (0.7%)
Rhabdomyolysis	1/79 (1.3%)		5/150 (3.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	0/79 (0%)		1/150 (0.7%)
Basal cell carcinoma	0/79 (0%)		2/150 (1.3%)
Brain neoplasm	0/79 (0%)		1/150 (0.7%)
Invasive papillary breast carcinoma	1/79 (1.3%)		0/150 (0%)
Lung neoplasm	0/79 (0%)		1/150 (0.7%)
Malignant melanoma	0/79 (0%)		1/150 (0.7%)
Prostate cancer	0/79 (0%)		1/150 (0.7%)
Squamous cell carcinoma	0/79 (0%)		1/150 (0.7%)
Transitional cell carcinoma	0/79 (0%)		1/150 (0.7%)
Nervous system disorders
Cerebrovascular accident	1/79 (1.3%)		0/150 (0%)
Dysgeusia	0/79 (0%)		1/150 (0.7%)
Haemorrhage intracranial	1/79 (1.3%)		0/150 (0%)
Paraesthesia	0/79 (0%)		1/150 (0.7%)
Somnolence	0/79 (0%)		1/150 (0.7%)
Syncope	1/79 (1.3%)		2/150 (1.3%)
Psychiatric disorders
Bipolar disorder	1/79 (1.3%)		0/150 (0%)
Mental status changes	0/79 (0%)		1/150 (0.7%)
Renal and urinary disorders
Acute kidney injury	1/79 (1.3%)		0/150 (0%)
Bladder obstruction	0/79 (0%)		1/150 (0.7%)
Haematuria	0/79 (0%)		1/150 (0.7%)
Nephropathy toxic	0/79 (0%)		1/150 (0.7%)
Reproductive system and breast disorders
Uterine prolapse	0/79 (0%)		1/150 (0.7%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/79 (1.3%)		0/150 (0%)
Bronchitis chronic	0/79 (0%)		1/150 (0.7%)
Dyspnoea	1/79 (1.3%)		2/150 (1.3%)
Emphysema	0/79 (0%)		1/150 (0.7%)
Pleural effusion	1/79 (1.3%)		0/150 (0%)
Respiratory arrest	0/79 (0%)		1/150 (0.7%)
Rhinorrhoea	0/79 (0%)		1/150 (0.7%)
Sputum discoloured	0/79 (0%)		1/150 (0.7%)
Skin and subcutaneous tissue disorders
Skin lesion	0/79 (0%)		1/150 (0.7%)
Vascular disorders
Arterial haemorrhage	0/79 (0%)		1/150 (0.7%)
Deep vein thrombosis	0/79 (0%)		2/150 (1.3%)
Hypotension	1/79 (1.3%)		1/150 (0.7%)
Orthostatic hypotension	1/79 (1.3%)		0/150 (0%)
Other (Not Including Serious) Adverse Events
	LDE225 200 mg qd		LDE225 800 mg qd
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/79 (96.2%)		145/150 (96.7%)
Blood and lymphatic system disorders
Anaemia	4/79 (5.1%)		13/150 (8.7%)
Ear and labyrinth disorders
Vertigo	0/79 (0%)		11/150 (7.3%)
Gastrointestinal disorders
Abdominal pain	8/79 (10.1%)		9/150 (6%)
Abdominal pain upper	7/79 (8.9%)		12/150 (8%)
Constipation	6/79 (7.6%)		24/150 (16%)
Diarrhoea	25/79 (31.6%)		34/150 (22.7%)
Dry mouth	4/79 (5.1%)		8/150 (5.3%)
Nausea	31/79 (39.2%)		71/150 (47.3%)
Vomiting	9/79 (11.4%)		41/150 (27.3%)
General disorders
Asthenia	10/79 (12.7%)		9/150 (6%)
Fatigue	26/79 (32.9%)		55/150 (36.7%)
Pyrexia	4/79 (5.1%)		5/150 (3.3%)
Infections and infestations
Influenza	4/79 (5.1%)		8/150 (5.3%)
Nasopharyngitis	8/79 (10.1%)		17/150 (11.3%)
Pneumonia	4/79 (5.1%)		3/150 (2%)
Upper respiratory tract infection	5/79 (6.3%)		11/150 (7.3%)
Urinary tract infection	7/79 (8.9%)		7/150 (4.7%)
Injury, poisoning and procedural complications
Fall	5/79 (6.3%)		5/150 (3.3%)
Investigations
Blood creatine phosphokinase increased	23/79 (29.1%)		54/150 (36%)
Lipase increased	6/79 (7.6%)		13/150 (8.7%)
Weight decreased	24/79 (30.4%)		64/150 (42.7%)
Metabolism and nutrition disorders
Decreased appetite	18/79 (22.8%)		52/150 (34.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	13/79 (16.5%)		17/150 (11.3%)
Back pain	6/79 (7.6%)		16/150 (10.7%)
Muscle spasms	43/79 (54.4%)		104/150 (69.3%)
Muscular weakness	4/79 (5.1%)		8/150 (5.3%)
Musculoskeletal pain	4/79 (5.1%)		7/150 (4.7%)
Myalgia	15/79 (19%)		42/150 (28%)
Pain in extremity	5/79 (6.3%)		8/150 (5.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	4/79 (5.1%)		5/150 (3.3%)
Nervous system disorders
Ageusia	1/79 (1.3%)		15/150 (10%)
Dizziness	7/79 (8.9%)		15/150 (10%)
Dysgeusia	35/79 (44.3%)		89/150 (59.3%)
Headache	12/79 (15.2%)		20/150 (13.3%)
Hypogeusia	0/79 (0%)		9/150 (6%)
Paraesthesia	4/79 (5.1%)		6/150 (4%)
Psychiatric disorders
Depression	5/79 (6.3%)		9/150 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	7/79 (8.9%)		11/150 (7.3%)
Oropharyngeal pain	4/79 (5.1%)		6/150 (4%)
Skin and subcutaneous tissue disorders
Alopecia	39/79 (49.4%)		87/150 (58%)
Pruritus	6/79 (7.6%)		12/150 (8%)
Vascular disorders
Hypertension	8/79 (10.1%)		16/150 (10.7%)

Limitations/Caveats

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.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.