A Phase II Study of Oral LDE225 in Patients With Hedge-Hog (Hh)-Pathway Activated Relapsed Medulloblastoma (MB)
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01708174
Collaborator
(none)
22
41
2
41
0.5
0
Study Details
Study Description
Brief Summary
This Phase II study evaluated the safety and efficacy of LDE225 in adult and pediatric patients with Hh-pathway activated, relapsed MB.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This study was a single-arm study of the efficacy and safety of oral sonidegib in patients with Hh-pathway activated relapsed medulloblastoma. It was initially designed as a randomized, controlled, open-label phase III study of adults and children with Hh-pathway activated MB whose disease had failed standard of care therapy, including radiation therapy (RT). The original study consisted of a randomized controlled part and a non-randomized uncontrolled part. Approximately 69 patients were to be randomized in a 2:1 ratio to receive sonidegib oral suspension or the active control, temozolomide (TMZ) capsules. Randomization was to be stratified according to age, <18 years versus ≥ 18 years. Approximately 40 patients were to receive sonidegib in the non-randomized uncontrolled part of the study. Following the enrollment of 11 patients, the study was amended to become a phase II single-arm study with only sonidegib, and the target enrollment was changed to 20 patients. Prior to the study amendment, TMZ participants whose disease progressed while on TMZ were permitted to crossover to sonidegib. After the amendment, participants receiving TMZ were crossed over to sonidegib.
Study Design
Study Type:
Interventional
Actual Enrollment
:
22 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Multi-center, Open-label, Single-arm Study of the Efficacy and Safety of Oral LDE225 in Patients With Hh-pathway Activated Relapsed Medulloblastoma
Actual Study Start Date
:
May 6, 2013
Actual Primary Completion Date
:
Oct 5, 2016
Actual Study Completion Date
:
Oct 5, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sonidegib (LDE225) 600 mg orally for adults and 500 mg/m2 orally for children |
Drug: LDE225
Sonidegib for oral suspension was supplied in amber glass bottles. Sonidegib oral suspension was combined with the supplied reconstitution vehicle to a final concentration of 50 mg/mL.
|
| Active Comparator: Temozolamide (TMZ) 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. |
Drug: TMZ
Temozolomide capsules were obtained locally by the Investigator
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 [from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016]
ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). Assessments after crossover were not included for TMZ participants.
Secondary Outcome Measures
- Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 [from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016]
PFS was defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). TMZ participants without event prior to crossover were censored.
- PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 [from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016]
PFS was defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause. PFS was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma.
- Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 [from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016]
ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). ORR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. Assessments after crossover were not included for TMZ patients.
- Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 [from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016]
DoR was defined as the time from the first documented onset of confirmed PR or CR to the date of PD/relapse or death due to medulloblastoma. DoR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. TMZ participants without an event prior to crossover were censored.
- Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 [from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016]
OS was defined as the time from date of randomization to date of death due to any cause. All deaths are considered, including deaths occurred after crossover for TMZ participants.
- Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) [Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49 and 53]
Blood samples were collected for assessment. The children's group was analyzed up until week 25 only.
Eligibility Criteria
Criteria
Ages Eligible for Study:
4 Months
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with histologically confirmed diagnosis of MB, who have experienced relapse or progression after standard-of-care therapy including radiotherapy. Patients currently receiving steroids must have been on a stable (or decreasing) dose for at least 5 days before initiating study therapy.
-
Only patients with a test result, using the 5-gene Hh signature assay, indicating Hhpathway activated MB are eligible for this study. All available tumor material obtained at any time during the course of the patient's disease should be submitted for these analyses
-
At least one measurable lesion defined as lesion(s) that can be accurately measured in at least two dimensions and is ≥ 10 mm in each dimension by Gadolinium (Gd)-MRI, irrespective of slice thickness/reconstruction interval, for CNS lesions and CT or MRI (with or without contrast) for non-CNS lesions. All patients with CNS lesions must have a brain MRI with and without gadolinium and a spine MRI with gadolinium within 2 weeks prior to first dose of study treatment.
-
Performance Status corresponding to ECOG score of 0, 1, or 2:
-
Karnofsky performance status score ≥ 50 for patients >16 years of age
-
Lansky performance status score ≥ 50 for patients ≤ 16 years of age
- Adequate bone marrow function as defined as:
-
Peripheral absolute neutrophil count (ANC) ≥ 1.5 x 109/L
-
Platelet count ≥ 80 x 109/L
-
Hemoglobin (Hgb) ≥ 9 g/dL
- Serum CK ≤1.5 ULN
Exclusion Criteria:
-
Prior treatment with a Smoothened inhibitor Systemic anticancer treatment within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies).
-
Focal radiation therapy within 4 weeks before first dose of study treatment, or full spinal radiotherapy within 3 months before first dose of study treatment.
-
Patients who have neuromuscular disorders that are associated with elevated CK (eg, inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
-
Patients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 or are metabolized by CYP2B6 and CYP2C9, that have narrow therapeutic indices that cannot be discontinued at least 2 weeks before first dose of study treatment and for the duration of the study
-
Patients receiving unstable or increasing doses of corticosteroids. If patients are on corticosteroids for endocrine deficiencies or tumor-associated symptoms, dose must have been stabilized (or decreasing) for at least 5 days before first dose of study treatment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ann & Robert H. Lurie Children Dept of Oncology | Chicago | Illinois | United States | 60611 |
| 2 | Sidney Kimmel Comprehensive Cancer Center/Johns Hopkins Med. Dept Onc | Baltimore | Maryland | United States | 21231 |
| 3 | Dana Farber Cancer Institute SC-7 | Boston | Massachusetts | United States | 02215 |
| 4 | Columbia University Medical Center- New York Presbyterian Dept of Oncology | New York | New York | United States | 10032 |
| 5 | Cincinnati Children's Hospital Medical Center Division of Hema/Onco. | Cincinnati | Ohio | United States | 45229-3039 |
| 6 | Children's Hospital of Pittsburgh Dept of Oncology | Pittsburgh | Pennsylvania | United States | 15213-2583 |
| 7 | University of Texas/MD Anderson Cancer Center SC-3 | Houston | Texas | United States | 77030-4009 |
| 8 | Seattle Cancer Care Alliance Dept Oncology | Seattle | Washington | United States | 98105 |
| 9 | Novartis Investigative Site | Herston | Queensland | Australia | 4029 |
| 10 | Novartis Investigative Site | Perth | Western Australia | Australia | 6840 |
| 11 | Novartis Investigative Site | Sao Paulo | SP | Brazil | |
| 12 | Novartis Investigative Site | Toronto | Ontario | Canada | M5G 1X8 |
| 13 | Novartis Investigative Site | Toronto | Ontario | Canada | M5G 1Z6 |
| 14 | Novartis Investigative Site | Bordeaux | Aquitaine | France | 33076 |
| 15 | Novartis Investigative Site | Angers Cedex 1 | France | 49033 | |
| 16 | Novartis Investigative Site | Lille Cedex | France | 59020 | |
| 17 | Novartis Investigative Site | Paris | France | 75231 | |
| 18 | Novartis Investigative Site | Toulouse Cedex 9 | France | 31059 | |
| 19 | Novartis Investigative Site | Vandoeuvre les Nancy | France | 54511 | |
| 20 | Novartis Investigative Site | Villejuif Cedex | France | 94805 | |
| 21 | Novartis Investigative Site | Augsburg | Germany | 86156 | |
| 22 | Novartis Investigative Site | Essen | Germany | 45147 | |
| 23 | Novartis Investigative Site | Hamburg | Germany | 20246 | |
| 24 | Novartis Investigative Site | Bologna | BO | Italy | 40139 |
| 25 | Novartis Investigative Site | Milano | MI | Italy | 20133 |
| 26 | Novartis Investigative Site | Roma | RM | Italy | 00165 |
| 27 | Novartis Investigative Site | Torino | TO | Italy | 101126 |
| 28 | Novartis Investigative Site | Torino | TO | Italy | 10126 |
| 29 | Novartis Investigative Site | Rotterdam | Netherlands | 3015 CN | |
| 30 | Novartis Investigative Site | Rotterdam | Netherlands | 3075 EA | |
| 31 | Novartis Investigative Site | Moskow | Russia | Russian Federation | 117198 |
| 32 | Novartis Investigative Site | Sevilla | Andalucia | Spain | 41013 |
| 33 | Novartis Investigative Site | Barcelona | Catalunya | Spain | 08035 |
| 34 | Novartis Investigative Site | Esplugues de Llobregat | Catalunya | Spain | 08950 |
| 35 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46026 |
| 36 | Novartis Investigative Site | Madrid | Spain | 28009 | |
| 37 | Novartis Investigative Site | Madrid | Spain | 28046 | |
| 38 | Novartis Investigative Site | Goteborg | Sweden | 413 45 | |
| 39 | Novartis Investigative Site | Zürich | Switzerland | 8032 | |
| 40 | Novartis Investigative Site | Sutton | Surrey | United Kingdom | SM2 5PT |
| 41 | Novartis Investigative Site | Leeds | United Kingdom | LS9 7TF |
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:
NCT01708174
Other Study ID Numbers:
- CLDE225C2301
First Posted:
Oct 16, 2012
Last Update Posted:
Aug 11, 2017
Last Verified:
Aug 1, 2017
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Analyses were performed by treatment and by age group. |
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) |
|---|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. |
| Period Title: Treatment Period | |||
| STARTED | 2 | 16 | 4 |
| Pharmacokinetic Analysis Set | 2 | 13 | 0 |
| COMPLETED | 1 | 14 | 3 |
| NOT COMPLETED | 1 | 2 | 1 |
| Period Title: Treatment Period | |||
| STARTED | 1 | 10 | 0 |
| COMPLETED | 1 | 10 | 0 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) | Total |
|---|---|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. | Total of all reporting groups |
| Overall Participants | 2 | 16 | 4 | 22 |
| Age (Years) [Median (Full Range) ] | ||||
| Median (Full Range) [Years] |
8.5
(6.36)
|
37.0
(8.17)
|
35.5
(3.16)
|
35.0
(10.73)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
2
100%
|
5
31.3%
|
2
50%
|
9
40.9%
|
| Male |
0
0%
|
11
68.8%
|
2
50%
|
13
59.1%
|
Outcome Measures
| Title | Percentage of Participants With Overall Response Rate (ORR) According to Independent Review Committee (IRC) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 |
|---|---|
| Description | ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). Assessments after crossover were not included for TMZ participants. |
| Time Frame | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) |
|---|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. |
| Measure Participants | 2 | 16 | 4 |
| Number [Percentage of participants] |
0.0
0%
|
18.8
117.5%
|
0.0
0%
|
| Title | Progression Free Survival (PFS) According to IRC From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 |
|---|---|
| Description | PFS was defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause (as per tumor response guidelines and criteria for Medulloblastoma). The IRC evaluated all radiological images and applicable clinical data (i.e., neurological examination, steroid use and cerebrospinal fluid (CSF) results as applicable). TMZ participants without event prior to crossover were censored. |
| Time Frame | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) |
|---|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. |
| Measure Participants | 2 | 16 | 4 |
| Median (95% Confidence Interval) [months] |
1.6
|
3.3
|
2.9
|
| Title | PFS According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 |
|---|---|
| Description | PFS was defined as the time from date of randomization to the date of event defined as the first documented progression or death due to any cause. PFS was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. |
| Time Frame | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The FAS was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) |
|---|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. |
| Measure Participants | 2 | 16 | 4 |
| Median (95% Confidence Interval) [months] |
NA
|
3.3
|
2.9
|
| Title | Percentage of Participants With ORR According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 |
|---|---|
| Description | ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). ORR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. Assessments after crossover were not included for TMZ patients. |
| Time Frame | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) |
|---|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. |
| Measure Participants | 2 | 16 | 4 |
| Number [Percentage of participants] |
0.0
0%
|
25.0
156.3%
|
0.0
0%
|
| Title | Duration of Response (DoR) According to Local Investigator Assessment From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 |
|---|---|
| Description | DoR was defined as the time from the first documented onset of confirmed PR or CR to the date of PD/relapse or death due to medulloblastoma. DoR was evaluated by local Investigator assessment per tumor response guidelines and criteria for Medulloblastoma. TMZ participants without an event prior to crossover were censored. |
| Time Frame | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) |
|---|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. |
| Measure Participants | 2 | 16 | 4 |
| Median (95% Confidence Interval) [months] |
NA
|
8.5
|
NA
|
| Title | Overall Survival (OS) From Date First Participant Randomized, 13-Sep-2013 to Date of Data Cut-off, 15-Nov-2016 |
|---|---|
| Description | OS was defined as the time from date of randomization to date of death due to any cause. All deaths are considered, including deaths occurred after crossover for TMZ participants. |
| Time Frame | from date first participant randomized, 13-Sep-2013 to date of data cut-off, 15-Nov-2016 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Temozolomide (TMZ) |
|---|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. |
| Measure Participants | 2 | 16 | 4 |
| Median (95% Confidence Interval) [months] |
NA
|
9.5
|
NA
|
| Title | Pharmacokinetics (PK): Summary of Plasma Trough Concentrations for Sonidegib (LDE225) |
|---|---|
| Description | Blood samples were collected for assessment. The children's group was analyzed up until week 25 only. |
| Time Frame | Weeks 1, 3, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49 and 53 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) was analyzed. The FAS included all randomized and non-randomized participants who received at least one dose of study treatment. |
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults |
|---|---|---|
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally |
| Measure Participants | 2 | 13 |
| Week 1 (n=2,11) |
0.00
(0.00)
|
0.00
(0.00)
|
| Week 3 (n=2,10) |
2890
(1240)
|
761
(519)
|
| Week 5 (n=2,8) |
4930
(1380)
|
1090
(700)
|
| Week 7 (n=1,8) |
2810
(NA)
|
1450
(842)
|
| Week 9 (n=1,8) |
4670
(NA)
|
1530
(682)
|
| Week 13 (n=1,4) |
3680
(NA)
|
2330
(1100)
|
| Week 17 (n=1,6) |
3060
(NA)
|
1880
(730)
|
| Week 21 (n=1,5) |
3770
(NA)
|
2270
(915)
|
| Week 25 (n=1,4) |
1890
(NA)
|
2050
(625)
|
| Week 29 (n=NA,4) |
NA
(NA)
|
2050
(906)
|
| Week 33 (n=NA,4) |
NA
(NA)
|
2180
(512)
|
| Week 37 (n=NA,3) |
NA
(NA)
|
2850
(306)
|
| Week 41 (n=NA,4) |
NA
(NA)
|
2370
(916)
|
| Week 45 (n=NA,2) |
NA
(NA)
|
2890
(290)
|
| Week 49 (n=NA,2) |
NA
(NA)
|
2330
(990)
|
| Week 53 (n=NA,2) |
NA
(NA)
|
2080
(764)
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Sonidegib (Total) | Temozolomide (TMZ) | ||||
| Arm/Group Description | 500 mg/m2 orally | 600 mg orally | Sonidegib (Total) | 150 to 200 mg/m2 for 5 sequential days every 4 weeks according to prescribing information until the study was amended to a single arm study. | ||||
All Cause Mortality |
||||||||
| Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Sonidegib (Total) | Temozolomide (TMZ) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Sonidegib (Total) | Temozolomide (TMZ) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/2 (100%) | 9/16 (56.3%) | 11/18 (61.1%) | 1/4 (25%) | ||||
| Gastrointestinal disorders | ||||||||
| NAUSEA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| VOMITING | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| General disorders | ||||||||
| GENERAL PHYSICAL HEALTH DETERIORATION | 1/2 (50%) | 0/16 (0%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PAIN | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Infections and infestations | ||||||||
| BACTERIAL SEPSIS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| CLOSTRIDIAL INFECTION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| LUNG INFECTION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| SEPSIS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Investigations | ||||||||
| ASPARTATE AMINOTRANSFERASE INCREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| DEHYDRATION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPERNATRAEMIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPONATRAEMIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| BACK PAIN | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| NECK PAIN | 0/2 (0%) | 0/16 (0%) | 0/18 (0%) | 1/4 (25%) | ||||
| Nervous system disorders | ||||||||
| SEIZURE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Product Issues | ||||||||
| THROMBOSIS IN DEVICE | 1/2 (50%) | 0/16 (0%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Psychiatric disorders | ||||||||
| CONFUSIONAL STATE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| DRUG DEPENDENCE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HALLUCINATION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| COUGH | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| DYSPNOEA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Vascular disorders | ||||||||
| EMBOLISM | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Sonidegib (LDE225) Children | Sonidegib (LDE225) Adults | Sonidegib (Total) | Temozolomide (TMZ) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/2 (100%) | 16/16 (100%) | 18/18 (100%) | 4/4 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| ANAEMIA | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| THROMBOCYTOPENIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Cardiac disorders | ||||||||
| ATRIOVENTRICULAR BLOCK FIRST DEGREE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| SINUS TACHYCARDIA | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| EAR CONGESTION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| VERTIGO | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Endocrine disorders | ||||||||
| DIABETES INSIPIDUS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Eye disorders | ||||||||
| DIPLOPIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PHOTOPHOBIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| VISION BLURRED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| ABDOMINAL DISTENSION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| ABDOMINAL PAIN | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 1/4 (25%) | ||||
| ABDOMINAL PAIN UPPER | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| AEROPHAGIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| ANAL INCONTINENCE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| CONSTIPATION | 0/2 (0%) | 6/16 (37.5%) | 6/18 (33.3%) | 1/4 (25%) | ||||
| DIARRHOEA | 1/2 (50%) | 3/16 (18.8%) | 4/18 (22.2%) | 0/4 (0%) | ||||
| DYSPHAGIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HAEMATOCHEZIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| NAUSEA | 0/2 (0%) | 5/16 (31.3%) | 5/18 (27.8%) | 3/4 (75%) | ||||
| PARAESTHESIA ORAL | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| REGURGITATION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| TOOTH DISCOLOURATION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| TOOTH LOSS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| VOMITING | 2/2 (100%) | 7/16 (43.8%) | 9/18 (50%) | 1/4 (25%) | ||||
| General disorders | ||||||||
| ASTHENIA | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 1/4 (25%) | ||||
| FATIGUE | 0/2 (0%) | 7/16 (43.8%) | 7/18 (38.9%) | 2/4 (50%) | ||||
| GAIT DISTURBANCE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| NON-CARDIAC CHEST PAIN | 0/2 (0%) | 0/16 (0%) | 0/18 (0%) | 1/4 (25%) | ||||
| OEDEMA PERIPHERAL | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 1/4 (25%) | ||||
| PAIN | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| PYREXIA | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| Immune system disorders | ||||||||
| ALLERGY TO ARTHROPOD BITE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Infections and infestations | ||||||||
| ACINETOBACTER INFECTION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| FOLLICULITIS | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| ORAL HERPES | 1/2 (50%) | 0/16 (0%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| RHINITIS | 0/2 (0%) | 0/16 (0%) | 0/18 (0%) | 1/4 (25%) | ||||
| UPPER RESPIRATORY TRACT INFECTION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| URINARY TRACT INFECTION | 0/2 (0%) | 4/16 (25%) | 4/18 (22.2%) | 0/4 (0%) | ||||
| Investigations | ||||||||
| ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| ALANINE AMINOTRANSFERASE INCREASED | 0/2 (0%) | 3/16 (18.8%) | 3/18 (16.7%) | 0/4 (0%) | ||||
| ASPARTATE AMINOTRANSFERASE INCREASED | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| BLOOD ALKALINE PHOSPHATASE INCREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 1/2 (50%) | 7/16 (43.8%) | 8/18 (44.4%) | 1/4 (25%) | ||||
| BLOOD CREATINE PHOSPHOKINASE MB INCREASED | 1/2 (50%) | 1/16 (6.3%) | 2/18 (11.1%) | 1/4 (25%) | ||||
| BLOOD CREATININE INCREASED | 0/2 (0%) | 3/16 (18.8%) | 3/18 (16.7%) | 0/4 (0%) | ||||
| BLOOD PHOSPHORUS INCREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| BODY TEMPERATURE INCREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| C-REACTIVE PROTEIN INCREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| CRYSTAL URINE PRESENT | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| GRANULOCYTE COUNT INCREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| LYMPHOCYTE COUNT DECREASED | 0/2 (0%) | 5/16 (31.3%) | 5/18 (27.8%) | 1/4 (25%) | ||||
| OXYGEN SATURATION DECREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PLATELET COUNT DECREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 1/4 (25%) | ||||
| PROTHROMBIN TIME PROLONGED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| RED BLOOD CELL COUNT DECREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| RED BLOOD CELL SEDIMENTATION RATE INCREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| WEIGHT DECREASED | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 1/4 (25%) | ||||
| WHITE BLOOD CELL COUNT DECREASED | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| DECREASED APPETITE | 0/2 (0%) | 4/16 (25%) | 4/18 (22.2%) | 0/4 (0%) | ||||
| FAILURE TO THRIVE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPERCALCAEMIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPERGLYCAEMIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPERURICAEMIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPOALBUMINAEMIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPOCALCAEMIA | 0/2 (0%) | 3/16 (18.8%) | 3/18 (16.7%) | 0/4 (0%) | ||||
| HYPOKALAEMIA | 0/2 (0%) | 4/16 (25%) | 4/18 (22.2%) | 0/4 (0%) | ||||
| HYPOMAGNESAEMIA | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| HYPONATRAEMIA | 0/2 (0%) | 3/16 (18.8%) | 3/18 (16.7%) | 0/4 (0%) | ||||
| HYPOPHOSPHATAEMIA | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| ARTHRALGIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| BACK PAIN | 0/2 (0%) | 4/16 (25%) | 4/18 (22.2%) | 0/4 (0%) | ||||
| MUSCLE SPASMS | 0/2 (0%) | 4/16 (25%) | 4/18 (22.2%) | 0/4 (0%) | ||||
| MYALGIA | 1/2 (50%) | 5/16 (31.3%) | 6/18 (33.3%) | 0/4 (0%) | ||||
| NECK PAIN | 0/2 (0%) | 3/16 (18.8%) | 3/18 (16.7%) | 1/4 (25%) | ||||
| PAIN IN EXTREMITY | 1/2 (50%) | 2/16 (12.5%) | 3/18 (16.7%) | 1/4 (25%) | ||||
| Nervous system disorders | ||||||||
| APHASIA | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| ATAXIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 1/4 (25%) | ||||
| CEREBROSPINAL FLUID LEAKAGE | 0/2 (0%) | 0/16 (0%) | 0/18 (0%) | 1/4 (25%) | ||||
| DEPRESSED LEVEL OF CONSCIOUSNESS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| DIZZINESS | 0/2 (0%) | 3/16 (18.8%) | 3/18 (16.7%) | 1/4 (25%) | ||||
| DROOLING | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| DYSARTHRIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 1/4 (25%) | ||||
| DYSGEUSIA | 0/2 (0%) | 5/16 (31.3%) | 5/18 (27.8%) | 0/4 (0%) | ||||
| FACIAL NERVE DISORDER | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HEADACHE | 2/2 (100%) | 3/16 (18.8%) | 5/18 (27.8%) | 1/4 (25%) | ||||
| HEMIPARESIS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| IIIRD NERVE DISORDER | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| LETHARGY | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| MUSCLE SPASTICITY | 1/2 (50%) | 1/16 (6.3%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| MYOCLONUS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| NEUROPATHY PERIPHERAL | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| NYSTAGMUS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PARAESTHESIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PERIPHERAL MOTOR NEUROPATHY | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PYRAMIDAL TRACT SYNDROME | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| SCIATICA | 0/2 (0%) | 0/16 (0%) | 0/18 (0%) | 1/4 (25%) | ||||
| SOMNOLENCE | 0/2 (0%) | 3/16 (18.8%) | 3/18 (16.7%) | 0/4 (0%) | ||||
| SYNCOPE | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Psychiatric disorders | ||||||||
| CONFUSIONAL STATE | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| DELIRIUM | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| DEPRESSION | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| INSOMNIA | 0/2 (0%) | 3/16 (18.8%) | 3/18 (16.7%) | 0/4 (0%) | ||||
| IRRITABILITY | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Renal and urinary disorders | ||||||||
| HAEMATURIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| MICTURITION URGENCY | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PROTEINURIA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| URINARY RETENTION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| APNOEA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| ATELECTASIS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| COUGH | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| DYSPNOEA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| EPISTAXIS | 0/2 (0%) | 0/16 (0%) | 0/18 (0%) | 1/4 (25%) | ||||
| PNEUMONITIS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PRODUCTIVE COUGH | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| ALOPECIA | 2/2 (100%) | 6/16 (37.5%) | 8/18 (44.4%) | 0/4 (0%) | ||||
| DERMATITIS ACNEIFORM | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 1/4 (25%) | ||||
| DRY SKIN | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| ERYTHEMA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPERHIDROSIS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| PRURITUS | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| RASH | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| RASH MACULO-PAPULAR | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| Vascular disorders | ||||||||
| HAEMATOMA | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPERTENSION | 0/2 (0%) | 1/16 (6.3%) | 1/18 (5.6%) | 0/4 (0%) | ||||
| HYPOTENSION | 0/2 (0%) | 2/16 (12.5%) | 2/18 (11.1%) | 0/4 (0%) | ||||
| THROMBOSIS | 1/2 (50%) | 0/16 (0%) | 1/18 (5.6%) | 0/4 (0%) | ||||
Limitations/Caveats
[Not Specified]
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 the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01708174
Other Study ID Numbers:
- CLDE225C2301
First Posted:
Oct 16, 2012
Last Update Posted:
Aug 11, 2017
Last Verified:
Aug 1, 2017