Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase III Study of RAD001 Adjuvant Therapy in Poor Risk Patients With Diffuse Large B-Cell Lymphoma (DLBCL) of RAD001 Versus Matching Placebo After Patients Have Achieved Complete Response With First-line Rituximab-chemotherapy (PILLAR2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00790036
Recruitment Status : Completed
First Posted : November 13, 2008
Results First Posted : July 12, 2017
Last Update Posted : July 12, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Diffuse Large B-cell Lymphoma
Interventions Drug: Everolimus
Drug: Everolimus Placebo
Enrollment 742
Recruitment Details Considering a recruitment period of 53 months and a final primary analysis performed after an anticipated duration of 69 months after study start, 727 patients had to be included. Actual enrolled: 742.
Pre-assignment Details  
Arm/Group Title RAD001 (Everolimus)1 Placebo
Hide Arm/Group Description RAD001 10 mg (two 5 mg tablets), daily for 12 months Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months
Period Title: Overall Study
Started 372 370
Untreated Participants 4 [1] 6 [2]
Completed 177 [3] 249 [3]
Not Completed 195 121
Reason Not Completed
Abnormal lab values             3             2
Administrative problems             5             9
Adverse Event             113             44
Death             1             0
Disease progression             24             48
Lost to Follow-up             1             2
Protocol Violation             10             2
Withdrawal by Subject             18             7
Subject/guardian decision             20             7
[1]
not treated due to administrative problems, protocol deviation, and subject withdrawal of consent.
[2]
not treated due to administrative problems and subject withdrawal of consent.
[3]
completed = treatment duration completed as per protocol
Arm/Group Title RAD001 (Everolimus)1 Placebo Total
Hide Arm/Group Description RAD001 10 mg (two 5 mg tablets), daily for 12 months Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months Total of all reporting groups
Overall Number of Baseline Participants 372 370 742
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) includes all randomized patients.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 372 participants 370 participants 742 participants
60.6  (13.72) 60.9  (13.61) 60.7  (13.66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 372 participants 370 participants 742 participants
Female
204
  54.8%
166
  44.9%
370
  49.9%
Male
168
  45.2%
204
  55.1%
372
  50.1%
1.Primary Outcome
Title Disease-free Survival (DFS)
Hide Description DFS was defined as the time from date of randomization to the date of event defined as the first documented relapse of the disease or death due to any cause. Relapse was based on investigator assessment and was assigned only if: It was documented according to Cheson guidelines by an objective radiological assessment method; It was documented by a biopsy proven lymphoma including new or recurrent bone marrow involvement; A new anticancer therapy for lymphoma started with subsequent confirmation of the relapse within 4 weeks of the start of this anticancer therapy
Time Frame From date of randomization to the date of event defined as the first documented recurrence of the disease, or death due to any cause and up to 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) includes all randomized patients.
Arm/Group Title RAD001 (Everolimus)1 Placebo
Hide Arm/Group Description:
RAD001 10 mg (two 5 mg tablets), daily for 12 months
Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months
Overall Number of Participants Analyzed 372 370
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
77.8
(72.7 to 82.1)
77.0
(72.1 to 81.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RAD001 (Everolimus)1, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.276
Comments P-value was obtained from the one-sided unstratified log rank test.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.69 to 1.22
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from date of randomization to date of death due to any cause. If the patient was not known to have died, survival was censored at the date of the last contact.
Time Frame From date of randomization to date of death due to any cause up to around 7 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) includes all randomized patients.
Arm/Group Title RAD001 (Everolimus)1 Placebo
Hide Arm/Group Description:
RAD001 10 mg (two 5 mg tablets), daily for 12 months
Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months
Overall Number of Participants Analyzed 372 370
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
2 years
90.7
(87.0 to 93.4)
88.3
(84.4 to 91.3)
3 years
88.0
(83.8 to 91.1)
83.7
(79.3 to 87.3)
4 years
85.4
(80.7 to 89.1)
80.7
(75.8 to 84.7)
5 years
83.4
(78.1 to 87.5)
77.4
(71.7 to 82.0)
6 years
80.3
(71.6 to 86.6)
77.4
(71.7 to 82.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RAD001 (Everolimus)1, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.52 to 1.09
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Lymphoma-specific Survival (LSS)
Hide Description LSS was defined as time from randomization to death as a result of lymphoma.
Time Frame From randomization to death documented as a result of lymphoma up to 7 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) includes all randomized patients.
Arm/Group Title RAD001 (Everolimus)1 Placebo
Hide Arm/Group Description:
RAD001 10 mg (two 5 mg tablets), daily for 12 months
Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months
Overall Number of Participants Analyzed 372 370
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
2 years
94.9
(91.8 to 96.8)
90.5
(86.9 to 93.2)
3 years
93.1
(89.6 to 95.5)
88.8
(84.9 to 91.8)
4 years
91.6
(87.6 to 94.3)
86.9
(82.6 to 90.3)
5 years
89.4
(84.6 to 92.8)
85.4
(80.5 to 89.2)
6 years
89.4
(84.6 to 92.8)
85.4
(80.5 to 89.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RAD001 (Everolimus)1, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.41 to 1.07
Estimation Comments [Not Specified]
Time Frame Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title RAD001 (Everolimus) Placebo All Patients
Hide Arm/Group Description RAD001 10 mg (two 5 mg tablets), daily for 12 months Everolimus placebo 10 mg (two 5 mg tablets), daily for 12 months All Patients in the Everolimus and Placebo groups.
All-Cause Mortality
RAD001 (Everolimus) Placebo All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
RAD001 (Everolimus) Placebo All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   105/368 (28.53%)   62/364 (17.03%)   167/732 (22.81%) 
Blood and lymphatic system disorders       
Anaemia  1  2/368 (0.54%)  1/364 (0.27%)  3/732 (0.41%) 
Autoimmune haemolytic anaemia  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Febrile neutropenia  1  8/368 (2.17%)  5/364 (1.37%)  13/732 (1.78%) 
Lymphopenia  1  2/368 (0.54%)  1/364 (0.27%)  3/732 (0.41%) 
Neutropenia  1  7/368 (1.90%)  4/364 (1.10%)  11/732 (1.50%) 
Pancytopenia  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Thrombocytopenia  1  0/368 (0.00%)  3/364 (0.82%)  3/732 (0.41%) 
Cardiac disorders       
Acute coronary syndrome  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Angina pectoris  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Angina unstable  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Atrial fibrillation  1  1/368 (0.27%)  2/364 (0.55%)  3/732 (0.41%) 
Atrial flutter  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Cardiac failure  1  4/368 (1.09%)  2/364 (0.55%)  6/732 (0.82%) 
Cardiac failure congestive  1  5/368 (1.36%)  1/364 (0.27%)  6/732 (0.82%) 
Cardiogenic shock  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Congestive cardiomyopathy  1  1/368 (0.27%)  1/364 (0.27%)  2/732 (0.27%) 
Left ventricular dysfunction  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Sinus node dysfunction  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Sinus tachycardia  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Tachycardia  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
Ear and labyrinth disorders       
Sudden hearing loss  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Eye disorders       
Cataract  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Diplopia  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Ophthalmoplegia  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Retinal detachment  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Vision blurred  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Gastrointestinal disorders       
Abdominal pain upper  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Anal fissure  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Constipation  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Crohn's disease  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Diarrhoea  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Duodenal ulcer  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Duodenal ulcer haemorrhage  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Inguinal hernia  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Intestinal obstruction  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Mouth ulceration  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Nausea  1  1/368 (0.27%)  1/364 (0.27%)  2/732 (0.27%) 
Oesophageal stenosis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Stomatitis  1  2/368 (0.54%)  1/364 (0.27%)  3/732 (0.41%) 
Vomiting  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
General disorders       
Disease progression  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Fatigue  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Oedema peripheral  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
Pyrexia  1  3/368 (0.82%)  2/364 (0.55%)  5/732 (0.68%) 
Sudden death  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hepatobiliary disorders       
Cholecystitis acute  1  2/368 (0.54%)  1/364 (0.27%)  3/732 (0.41%) 
Cholelithiasis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hepatic function abnormal  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Hepatotoxicity  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Immune system disorders       
Sarcoidosis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Infections and infestations       
Acute sinusitis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Atypical pneumonia  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Bronchitis  1  1/368 (0.27%)  1/364 (0.27%)  2/732 (0.27%) 
Cellulitis  1  2/368 (0.54%)  1/364 (0.27%)  3/732 (0.41%) 
Cytomegalovirus colitis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Device related infection  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Enteritis infectious  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Gastroenteritis  1  2/368 (0.54%)  1/364 (0.27%)  3/732 (0.41%) 
Hepatitis B  1  1/368 (0.27%)  2/364 (0.55%)  3/732 (0.41%) 
Herpes zoster  1  1/368 (0.27%)  1/364 (0.27%)  2/732 (0.27%) 
Implant site infection  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Influenza  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Localised infection  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Lung infection  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Moraxella infection  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Pneumocystis jirovecii pneumonia  1  3/368 (0.82%)  1/364 (0.27%)  4/732 (0.55%) 
Pneumonia  1  7/368 (1.90%)  3/364 (0.82%)  10/732 (1.37%) 
Pneumonia bacterial  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Pneumonia cryptococcal  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Pneumonia klebsiella  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Pulmonary tuberculosis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Pyelonephritis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Pyelonephritis acute  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Pyonephrosis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Respiratory tract infection  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Septic shock  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
Skin infection  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Systemic infection  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Tinea pedis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Tuberculosis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Upper respiratory tract infection  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Urinary tract infection  1  1/368 (0.27%)  3/364 (0.82%)  4/732 (0.55%) 
Injury, poisoning and procedural complications       
Contusion  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Fall  1  1/368 (0.27%)  3/364 (0.82%)  4/732 (0.55%) 
Femoral neck fracture  1  0/368 (0.00%)  2/364 (0.55%)  2/732 (0.27%) 
Femur fracture  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Humerus fracture  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Overdose  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Periorbital haematoma  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Post procedural haematoma  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Wrist fracture  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Investigations       
Alanine aminotransferase increased  1  1/368 (0.27%)  1/364 (0.27%)  2/732 (0.27%) 
Aspartate aminotransferase increased  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Biopsy lung  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Blood alkaline phosphatase increased  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Blood bilirubin increased  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Blood cholesterol increased  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
CD4 lymphocytes decreased  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
Gamma-glutamyltransferase increased  1  3/368 (0.82%)  0/364 (0.00%)  3/732 (0.41%) 
Lymphocyte count decreased  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Weight decreased  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Metabolism and nutrition disorders       
Dehydration  1  2/368 (0.54%)  1/364 (0.27%)  3/732 (0.41%) 
Diabetes mellitus  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hyperglycaemia  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Hyperlipidaemia  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hypocalcaemia  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hypokalaemia  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hyponatraemia  1  3/368 (0.82%)  0/364 (0.00%)  3/732 (0.41%) 
Metabolic acidosis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Myopathy  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Pain in extremity  1  1/368 (0.27%)  1/364 (0.27%)  2/732 (0.27%) 
Polyarthritis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acute myeloid leukaemia  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Bladder cancer  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Diffuse large B-cell lymphoma  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Papillary thyroid cancer  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Nervous system disorders       
Brachial plexopathy  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Central nervous system lesion  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Cerebral artery occlusion  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Cerebral haemorrhage  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Cerebral infarction  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Cerebrovascular accident  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Cerebrovascular insufficiency  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Cervicobrachial syndrome  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Diabetic neuropathy  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Dizziness  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Encephalomalacia  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Facial paresis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Haemorrhage intracranial  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Headache  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
IVth nerve paresis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Memory impairment  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Neuropathy peripheral  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Optic neuritis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Paraparesis  1  0/368 (0.00%)  2/364 (0.55%)  2/732 (0.27%) 
Peripheral motor neuropathy  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Seizure  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Somnolence  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Syncope  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Vascular dementia  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Vocal cord paresis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Product Issues       
Device difficult to use  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Psychiatric disorders       
Depression  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Mental status changes  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Renal and urinary disorders       
Acute kidney injury  1  2/368 (0.54%)  1/364 (0.27%)  3/732 (0.41%) 
Cystitis haemorrhagic  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Renal cyst  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Urinary incontinence  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Reproductive system and breast disorders       
Testicular swelling  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Uterine haemorrhage  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Dyspnoea  1  3/368 (0.82%)  2/364 (0.55%)  5/732 (0.68%) 
Granulomatous pneumonitis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hyperventilation  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Interstitial lung disease  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
Obliterative bronchiolitis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Pleural effusion  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
Pneumonitis  1  4/368 (1.09%)  1/364 (0.27%)  5/732 (0.68%) 
Pulmonary embolism  1  3/368 (0.82%)  0/364 (0.00%)  3/732 (0.41%) 
Respiratory failure  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
Rhinitis allergic  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Skin and subcutaneous tissue disorders       
Dermatitis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Erythema  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Erythema multiforme  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Palmar-plantar erythrodysaesthesia syndrome  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Pityriasis rosea  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Rash papular  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Toxic epidermal necrolysis  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Vascular disorders       
Arteriosclerosis  1  0/368 (0.00%)  2/364 (0.55%)  2/732 (0.27%) 
Deep vein thrombosis  1  2/368 (0.54%)  0/364 (0.00%)  2/732 (0.27%) 
Erythromelalgia  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Hypertension  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hypertensive crisis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Hypotension  1  0/368 (0.00%)  1/364 (0.27%)  1/732 (0.14%) 
Lymphoedema  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Thrombophlebitis  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Varicose ulceration  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Vein disorder  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Venous thrombosis limb  1  1/368 (0.27%)  0/364 (0.00%)  1/732 (0.14%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
RAD001 (Everolimus) Placebo All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   348/368 (94.57%)   276/364 (75.82%)   624/732 (85.25%) 
Blood and lymphatic system disorders       
Anaemia  1  61/368 (16.58%)  18/364 (4.95%)  79/732 (10.79%) 
Leukopenia  1  29/368 (7.88%)  23/364 (6.32%)  52/732 (7.10%) 
Lymphopenia  1  22/368 (5.98%)  13/364 (3.57%)  35/732 (4.78%) 
Neutropenia  1  89/368 (24.18%)  57/364 (15.66%)  146/732 (19.95%) 
Thrombocytopenia  1  55/368 (14.95%)  9/364 (2.47%)  64/732 (8.74%) 
Gastrointestinal disorders       
Abdominal pain  1  25/368 (6.79%)  21/364 (5.77%)  46/732 (6.28%) 
Aphthous ulcer  1  21/368 (5.71%)  4/364 (1.10%)  25/732 (3.42%) 
Constipation  1  19/368 (5.16%)  25/364 (6.87%)  44/732 (6.01%) 
Diarrhoea  1  99/368 (26.90%)  49/364 (13.46%)  148/732 (20.22%) 
Dry mouth  1  23/368 (6.25%)  5/364 (1.37%)  28/732 (3.83%) 
Mouth ulceration  1  57/368 (15.49%)  13/364 (3.57%)  70/732 (9.56%) 
Nausea  1  51/368 (13.86%)  37/364 (10.16%)  88/732 (12.02%) 
Stomatitis  1  166/368 (45.11%)  28/364 (7.69%)  194/732 (26.50%) 
Vomiting  1  34/368 (9.24%)  30/364 (8.24%)  64/732 (8.74%) 
General disorders       
Asthenia  1  37/368 (10.05%)  28/364 (7.69%)  65/732 (8.88%) 
Fatigue  1  66/368 (17.93%)  55/364 (15.11%)  121/732 (16.53%) 
Oedema peripheral  1  69/368 (18.75%)  25/364 (6.87%)  94/732 (12.84%) 
Pyrexia  1  62/368 (16.85%)  32/364 (8.79%)  94/732 (12.84%) 
Infections and infestations       
Nasopharyngitis  1  42/368 (11.41%)  32/364 (8.79%)  74/732 (10.11%) 
Pneumonia  1  23/368 (6.25%)  3/364 (0.82%)  26/732 (3.55%) 
Sinusitis  1  21/368 (5.71%)  11/364 (3.02%)  32/732 (4.37%) 
Upper respiratory tract infection  1  42/368 (11.41%)  27/364 (7.42%)  69/732 (9.43%) 
Urinary tract infection  1  20/368 (5.43%)  18/364 (4.95%)  38/732 (5.19%) 
Investigations       
Blood cholesterol increased  1  21/368 (5.71%)  5/364 (1.37%)  26/732 (3.55%) 
Blood lactate dehydrogenase increased  1  33/368 (8.97%)  5/364 (1.37%)  38/732 (5.19%) 
CD4 lymphocytes decreased  1  37/368 (10.05%)  18/364 (4.95%)  55/732 (7.51%) 
Weight decreased  1  28/368 (7.61%)  6/364 (1.65%)  34/732 (4.64%) 
Metabolism and nutrition disorders       
Decreased appetite  1  43/368 (11.68%)  19/364 (5.22%)  62/732 (8.47%) 
Hypercholesterolaemia  1  42/368 (11.41%)  13/364 (3.57%)  55/732 (7.51%) 
Hyperglycaemia  1  40/368 (10.87%)  26/364 (7.14%)  66/732 (9.02%) 
Hypertriglyceridaemia  1  32/368 (8.70%)  16/364 (4.40%)  48/732 (6.56%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  30/368 (8.15%)  31/364 (8.52%)  61/732 (8.33%) 
Back pain  1  22/368 (5.98%)  33/364 (9.07%)  55/732 (7.51%) 
Pain in extremity  1  25/368 (6.79%)  28/364 (7.69%)  53/732 (7.24%) 
Nervous system disorders       
Dizziness  1  21/368 (5.71%)  27/364 (7.42%)  48/732 (6.56%) 
Dysgeusia  1  25/368 (6.79%)  7/364 (1.92%)  32/732 (4.37%) 
Headache  1  42/368 (11.41%)  31/364 (8.52%)  73/732 (9.97%) 
Psychiatric disorders       
Insomnia  1  25/368 (6.79%)  16/364 (4.40%)  41/732 (5.60%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  65/368 (17.66%)  40/364 (10.99%)  105/732 (14.34%) 
Dyspnoea  1  32/368 (8.70%)  11/364 (3.02%)  43/732 (5.87%) 
Epistaxis  1  34/368 (9.24%)  2/364 (0.55%)  36/732 (4.92%) 
Pneumonitis  1  24/368 (6.52%)  1/364 (0.27%)  25/732 (3.42%) 
Skin and subcutaneous tissue disorders       
Pruritus  1  36/368 (9.78%)  22/364 (6.04%)  58/732 (7.92%) 
Rash  1  70/368 (19.02%)  31/364 (8.52%)  101/732 (13.80%) 
Vascular disorders       
Hypertension  1  19/368 (5.16%)  13/364 (3.57%)  32/732 (4.37%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of 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 ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00790036     History of Changes
Other Study ID Numbers: CRAD001N2301
2008-000498-40 ( EudraCT Number )
First Submitted: November 11, 2008
First Posted: November 13, 2008
Results First Submitted: June 14, 2017
Results First Posted: July 12, 2017
Last Update Posted: July 12, 2017