Trial Outcomes & Findings for Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors (NCT NCT00510068)
NCT ID: NCT00510068
Last Updated: 2015-07-01
Results Overview
Progression of disease is defined as the time from study start to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria: Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
410 participants
Primary outcome timeframe
Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010
Results posted on
2015-07-01
Participant Flow
Participant milestones
| Measure |
Everolimus 10 mg/Day
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Double-blind Period
STARTED
|
207
|
203
|
|
Double-blind Period
Safety Population
|
204
|
203
|
|
Double-blind Period
COMPLETED
|
0
|
0
|
|
Double-blind Period
NOT COMPLETED
|
207
|
203
|
|
Open-label Period
STARTED
|
225
|
0
|
|
Open-label Period
COMPLETED
|
0
|
0
|
|
Open-label Period
NOT COMPLETED
|
225
|
0
|
Reasons for withdrawal
| Measure |
Everolimus 10 mg/Day
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Double-blind Period
Disease progression
|
98
|
169
|
|
Double-blind Period
Final primary analysis
|
52
|
18
|
|
Double-blind Period
Adverse Event
|
37
|
7
|
|
Double-blind Period
Withdrawal by Subject
|
8
|
6
|
|
Double-blind Period
Death
|
4
|
3
|
|
Double-blind Period
Abnormal test result (s)
|
1
|
0
|
|
Double-blind Period
Lost to Follow-up
|
1
|
0
|
|
Double-blind Period
Protocol Violation
|
6
|
0
|
|
Open-label Period
Disease Progression
|
124
|
0
|
|
Open-label Period
Adverse Event
|
46
|
0
|
|
Open-label Period
Withdrawal by Subject
|
21
|
0
|
|
Open-label Period
Administrative problems
|
17
|
0
|
|
Open-label Period
Death
|
7
|
0
|
|
Open-label Period
New cancer therapy
|
7
|
0
|
|
Open-label Period
Protocol Violation
|
2
|
0
|
|
Open-label Period
Abnormal laboratory value (s)
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety of Everolimus (RAD001) Compared to Placebo in Patients With Advanced Neuroendocrine Tumors
Baseline characteristics by cohort
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
Total
n=410 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.1 years
STANDARD_DEVIATION 12.2 • n=5 Participants
|
56.2 years
STANDARD_DEVIATION 11.4 • n=7 Participants
|
56.6 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Age, Customized
<65 years
|
146 Participants
n=5 Participants
|
153 Participants
n=7 Participants
|
299 Participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
61 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
97 Participants
n=5 Participants
|
86 Participants
n=7 Participants
|
183 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
110 Participants
n=5 Participants
|
117 Participants
n=7 Participants
|
227 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
156 Participants
n=5 Participants
|
166 Participants
n=7 Participants
|
322 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
40 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
9 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010Population: The Full Analysis Set (FAS) consists of all patients who were randomized.
Progression of disease is defined as the time from study start to the date of first documented progression of disease or death due to any cause. Progression of disease is defined by RECIST criteria: Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Time to Progression Free Survival (PFS) Based as Per Investigator Using Kaplan-Meier Methodology
|
11.04 Months
Interval 8.41 to 13.86
|
4.60 Months
Interval 3.06 to 5.39
|
SECONDARY outcome
Timeframe: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010Population: The Full Analysis Set (FAS) consists of all patients who were randomized.
Objective Response defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of the longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks . Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Percentage of Participants With Objective Response Rate ( CR {Complete Response} OR PR {Partial Response})
|
4.8 Percentage of participants
Interval 2.3 to 8.7
|
2.0 Percentage of participants
Interval 0.5 to 5.0
|
SECONDARY outcome
Timeframe: Baseline, to death- no time limitPopulation: The Full Analysis Set (FAS) included all randomized patients.
Overall survival (OS) was defined as the time from date of randomization to the date of death due to any cause. Analyses were performed using all deaths in the FAS population regardless of whether they were observed during the double-blind treatment period, the open-label treatment period, the post-treatment evaluations, or the survival follow-up period.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Overall Survival
|
44.02 Months
Interval 35.61 to 51.75
|
37.68 Months
Interval 29.14 to 45.77
|
SECONDARY outcome
Timeframe: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010Population: The Full Analysis Set (FAS) consisted of all patients who were randomized.
The level of Ki 67 expression for evaluable tumor samples were analyzed towards progression free survival (PFS) as per local investigator assessment. The Ki-67 protein is a cellular marker for proliferation. It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chromosomes. Baseline Ki 67 levels were categorized as: less than or equal to 2%, \> 2% to less than or equal to 5% and \> 5%.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Progression Free Survival According to Ki-67 Levels Categorized as: Less Than or Equal to 2%, > 2% to Less Than or Equal to 5% and > 5%
Ki67 >5% (n: 20, 22)
|
7.69 Months
Interval 5.59 to
Upper boundary of the 95% (Confidence Interval (CI) was not computable
|
3.15 Months
Interval 2.79 to 5.55
|
|
Progression Free Survival According to Ki-67 Levels Categorized as: Less Than or Equal to 2%, > 2% to Less Than or Equal to 5% and > 5%
Ki67 <=2% (n: 7, 17)
|
12.52 Months
Interval 3.42 to 14.75
|
3.68 Months
Interval 2.86 to 5.52
|
|
Progression Free Survival According to Ki-67 Levels Categorized as: Less Than or Equal to 2%, > 2% to Less Than or Equal to 5% and > 5%
2% <Ki67 <=5% (n: 24, 13)
|
10.94 Months
Interval 5.55 to 16.59
|
8.48 Months
Interval 3.78 to 13.83
|
SECONDARY outcome
Timeframe: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010Population: The Full Analysis Set (FAS) consisted of all patients who were randomized.
Baseline levels of serum CgA SE were characterized towards progression free survival (PFS) as per local investigator assessment, relative to the upper limited of normal (ULN). CgA levels exceeding 2 x ULN were considered to be 'Elevated' otherwise considered as "Non-elevated". An 'early response' (applicable to only those patients with elevated levels at baseline) was defined as a decrease of greater than or equal to 30% from baseline to Cycle 2 Day 1 or normalization by Cycle 2 Day 1. CgA is widely expressed in well-differentiated pancreatic NET. CgA is present in the secretory granules of neuroendocrine cells. Pancreatic NET patients often present with elevated circulating levels of CgA in their blood. Baseline levels of these biomarkers are considered as prognostic factors.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response
CgA Levels at baseline: CgA <= 2x ULN (n:121, 97)
|
11.17 Months
Interval 8.54 to 16.49
|
4.90 Months
Interval 2.99 to 5.55
|
|
Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response
CgA levels at baseline: CgA > 2x ULN (n:84, 103)
|
8.54 Months
Interval 7.69 to 13.8
|
4.34 Months
Interval 2.86 to 5.39
|
|
Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response
Early CgA response: Response (n: 48, 22)
|
8.54 Months
Interval 7.56 to 14.0
|
5.70 Months
Interval 3.19 to 8.54
|
|
Progression Free Survival According to Chromogramin A Tumor Marker (CgA) Baseline Level and According to CgA Early Response
Early CgA response: Non-Response (n:40, 82)
|
11.14 Months
Interval 6.9 to
Upper boundary of the 95% Confidence Interval (CI) was not be computable
|
3.19 Months
Interval 2.83 to 5.36
|
SECONDARY outcome
Timeframe: Time from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 17 August 2007, until cut-off date 28 February 2010Population: The Full Analysis Set (FAS) consisted of all patients who were randomized.
Baseline levels of serum NSE were characterized towards PFS as per local investigator assessment, relative to the upper limited of normal (ULN). NSE levels exceeding ULN were considered to be 'Elevated' otherwise considered as "Non-elevated". An 'early response' (applicable to only those patients with elevated levels at baseline) was defined as a decrease of greater than or equal to 30% from baseline to Cycle 2 Day 1 or normalization by Cycle 2 Day 1. NSE is widely expressed in well-differentiated pancreatic NET. NSE is usually expressed in the cytoplasm. Pancreatic NET patients often present with elevated circulating levels of NSE in their blood. Baseline levels of these biomarkers are considered as prognostic factors.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response
NSE Levels at baseline: <= ULN (n: 155, 138)
|
13.86 Months
Interval 10.81 to 18.1
|
5.36 Months
Interval 3.78 to 5.55
|
|
Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response
NSE levels at baseline: > ULN (n: 48, 56)
|
8.11 Months
Interval 4.24 to 11.17
|
2.83 Months
Interval 2.6 to 3.06
|
|
Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response
Early NSE response: Response (n: 24, 16)
|
8.11 Months
Interval 4.24 to 11.4
|
3.06 Months
Interval 2.23 to 5.36
|
|
Progression Free Survival According to Neuron Specific Enolase Tumor Marker (NSE) Baseline Level and According to NSE Early Response
Early NSE response: Non-Response (n:16, 27)
|
3.79 Months
Interval 2.6 to 13.8
|
2.58 Months
Interval 1.84 to 2.83
|
SECONDARY outcome
Timeframe: on or after the start of double-blind study medication until no later than 28 days after double-blind study medication discontinuationPopulation: The Safety Set consists of all patients who received any study drug and had at least one post-baseline safety assessment.
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=204 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs)
Adverse events (AEs)
|
203 Participants
|
198 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs)
Death
|
111 Participants
|
23 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs)
Serious Adverse Events
|
84 Participants
|
52 Participants
|
SECONDARY outcome
Timeframe: on or after the start of open-label study medication until no later than 28 days after open-label study medication discontinuationPopulation: The open-label set was used to summarize the safety analyses performed on data collected in the open-label period of the study: the open-label set included only patients who received at least one dose of open-label everolimus 10 mg and had at least one safety assessment during the open-label period of the study.
Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=225 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) (Open-label Period)
Adverse events (AEs)
|
221 Participants
|
—
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) (Open-label Period)
Death
|
122 Participants
|
—
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) (Open-label Period)
Serious Adverse Events
|
108 Participants
|
—
|
SECONDARY outcome
Timeframe: Day 1 of every cycle (28 days/cycle) throughout the studyPopulation: The Safety Set consisted of all patients who received any study drug and had at least one postbaseline safety assessment.
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. This PK parameter is area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-t last).
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=7 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=1 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Evaluation of Pharmacokinetics (PK) Parameter: AUC0-t Last
|
594 ng.h/mL
Standard Deviation 313
|
481 ng.h/mL
Standard Deviation NA
Summary statistics were only produced if the sample size for the dose group in the respective cycle is 3 or more.
|
SECONDARY outcome
Timeframe: Day 1 of every cycle (28 days/cycle) throughout the studyPopulation: The Safety Set consisted of all patients who received any study drug and had at least one postbaseline safety assessment.
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameter: maximum (peak) drug concentration (Cmax) and minimum (trough) drug concentration (Cmin).
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=7 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=1 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Evaluation of Pharmacokinetics (PK) Parameters: Cmax, Cmin
Cmax
|
62.4 ng/mL
Standard Deviation 18.5
|
27.4 ng/mL
Standard Deviation NA
Summary statistics will only be produced if the sample size for the dose group in the respective cycle is 3 or more.
|
|
Evaluation of Pharmacokinetics (PK) Parameters: Cmax, Cmin
Cmin
|
9.80 ng/mL
Standard Deviation 4.95
|
12.2 ng/mL
Standard Deviation NA
Summary statistics will only be produced if the sample size for the dose group in the respective cycle is 3 or more.
|
SECONDARY outcome
Timeframe: Day 1 of every cycle (28 days/cycle) throughout the studyPopulation: The Safety Set consisted of all patients who received any study drug and had at least one postbaseline safety assessment.
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. The PK parameter clearance of distribution expressed as a function of bioavailability (CL/F).
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=7 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=1 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Evaluation of Pharmacokinetics (PK) Parameter: CL/F
|
20.2 L/h
Standard Deviation 7.7
|
10.7 L/h
Standard Deviation NA
Summary statistics were only produced if the sample size for the dose group in the respective cycle is 3 or more.
|
SECONDARY outcome
Timeframe: Day 1 of every cycle (28 days/cycle) throughout the studyPopulation: The Safety Set consisted of all patients who received any study drug and had at least one postbaseline safety assessment.
The PK parameters for a full PK profile at steady-state were determined in blood using non compartmental methods. Values for tmax where summarized in median (range).
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=7 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=1 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Evaluation of Pharmacokinetics (PK) Parameter: Tmax -Time to Maximum (Peak) Drug Concentration
|
1.17 h
Interval 0.5 to 24.0
|
3.0 h
Summary statistics were only produced if the sample size for the dose group in the respective cycle is 3 or more.
|
SECONDARY outcome
Timeframe: 3 months, 6 monthsPopulation: The Full Analysis Set (FAS) consists of all patients who were randomized.
Time to definitive worsening is defined as a definitive increase in performance status from a baseline of 0 or 1 to WHO \>= 2, or from a baseline value of 2 to WHO \>= 3. If no earlier deterioration, patients were censored at the end of follow-up or at the start of further antineoplastic therapy. Rates of patients with no deterioration at 3 and 6 months were computed using Kaplan-meier method. Grade 0: Able to carry out all activity without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory \& able to do light work; Grade 2: Ambulatory \& capable of all self-care but unable to carry out any work. Up \& about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled \& cannot carry on any self-care; totally confined to bed or chair.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Analysis of Time to Definitive Deterioration of WHO Performance Status Using Kaplan-Meier
Month 3
|
94.4 % of participants with no deterioration
Interval 90.0 to 96.8
|
91.8 % of participants with no deterioration
Interval 86.8 to 95.0
|
|
Analysis of Time to Definitive Deterioration of WHO Performance Status Using Kaplan-Meier
Month 6
|
90.6 % of participants with no deterioration
Interval 85.2 to 94.0
|
86.3 % of participants with no deterioration
Interval 79.3 to 91.0
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1Population: The Full Analysis Set (FAS) consists of all patients who were randomized.
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF)
Baseline (n:198, 195)
|
52.59 pg/mL
Standard Deviation 101.659
|
51.49 pg/mL
Standard Deviation 78.049
|
|
Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF)
Cycle 2 Day 1 (n: 185, 184)
|
38.43 pg/mL
Standard Deviation 51.809
|
58.33 pg/mL
Standard Deviation 72.938
|
|
Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF)
Cycle 3 Day 1 (n: 185, 174)
|
51.97 pg/mL
Standard Deviation 89.064
|
59.08 pg/mL
Standard Deviation 72.495
|
|
Plasma Angiogenesis Marker: Basic Fibroblast Growth Factor (bFGF)
Cycle 4 Day 1 (n: 171, 159)
|
51.28 pg/mL
Standard Deviation 82.139
|
54.58 pg/mL
Standard Deviation 75.350
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1Population: The Full Analysis Set (FAS) consists of all patients who were randomized.
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Plasma Angiogenesis Marker: Placental Growth Factor (PLGF)
Baseline (n:198, 195)
|
45.82 pg/mL
Standard Deviation 282.084
|
32.92 pg/mL
Standard Deviation 52.586
|
|
Plasma Angiogenesis Marker: Placental Growth Factor (PLGF)
Cycle 2 Day 1 (n: 185, 184)
|
25.78 pg/mL
Standard Deviation 33.420
|
35.38 pg/mL
Standard Deviation 57.135
|
|
Plasma Angiogenesis Marker: Placental Growth Factor (PLGF)
Cycle 3 Day 1 (n: 185, 174)
|
26.55 pg/mL
Standard Deviation 28.839
|
33.84 pg/mL
Standard Deviation 65.361
|
|
Plasma Angiogenesis Marker: Placental Growth Factor (PLGF)
Cycle 4 Day 1 (n: 171, 159)
|
25.69 pg/mL
Standard Deviation 18.312
|
35.47 pg/mL
Standard Deviation 67.314
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1Population: The Full Analysis Set (FAS) consists of all patients who were randomized.
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1)
Baseline (n:198, 195)
|
264.18 pg/mL
Standard Deviation 272.190
|
256.69 pg/mL
Standard Deviation 187.866
|
|
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1)
Cycle 2 Day 1 (n: 185, 184)
|
307.46 pg/mL
Standard Deviation 808.316
|
299.03 pg/mL
Standard Deviation 541.933
|
|
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1)
Cycle 3 Day 1 (n: 185, 174)
|
263.81 pg/mL
Standard Deviation 187.329
|
253.37 pg/mL
Standard Deviation 250.841
|
|
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1)
Cycle 4 Day 1 (n: 171, 159)
|
258.03 pg/mL
Standard Deviation 223.980
|
242.17 pg/mL
Standard Deviation 163.561
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1Population: The Full Analysis Set (FAS) consists of all patients who were randomized.
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)
Baseline (n:197, 193)
|
30061.30 pg/mL
Standard Deviation 8607.379
|
31299.61 pg/mL
Standard Deviation 9091.460
|
|
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)
Cycle 2 Day 1 (n: 185, 183)
|
22691.18 pg/mL
Standard Deviation 6793.409
|
30223.21 pg/mL
Standard Deviation 8447.992
|
|
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)
Cycle 3 Day 1 (n: 185, 173)
|
22021.23 pg/mL
Standard Deviation 6393.414
|
29264.67 pg/mL
Standard Deviation 8408.405
|
|
Plasma Angiogenesis Marker: Soluble Vascular Endothelial Growth Factor Receptor 2 (sVEGFR2)
Cycle 4 Day 1 (n: 172, 158)
|
21218.17 pg/mL
Standard Deviation 6249.977
|
28308.58 pg/mL
Standard Deviation 8477.049
|
SECONDARY outcome
Timeframe: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1Population: The Full Analysis Set (FAS) consists of all patients who were randomized.
This biomarker is related to angiogenesis pathway, was analyzed to determine the effects of everolimus on plasma antiangiogenic molecules.
Outcome measures
| Measure |
Everolimus 10 mg/Day
n=207 Participants
Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 Participants
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
|---|---|---|
|
Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF)
Cycle 2 Day 1 (n: 185, 184)
|
243.03 pg/mL
Standard Deviation 183.010
|
326.78 pg/mL
Standard Deviation 377.752
|
|
Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF)
Baseline (n:198, 195)
|
265.09 pg/mL
Standard Deviation 283.123
|
326.16 pg/mL
Standard Deviation 323.891
|
|
Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF)
Cycle 3 Day 1 (n: 185, 174)
|
280.18 pg/mL
Standard Deviation 268.582
|
292.27 pg/mL
Standard Deviation 286.154
|
|
Plasma Angiogenesis Marker: Vascular Endothelial Growth Factor (VEGF)
Cycle 4 Day 1 (n: 171, 159)
|
283.51 pg/mL
Standard Deviation 326.634
|
319.60 pg/mL
Standard Deviation 325.409
|
Adverse Events
Everolimus 10mg/Day
Serious events: 84 serious events
Other events: 201 other events
Deaths: 0 deaths
Placebo
Serious events: 52 serious events
Other events: 190 other events
Deaths: 0 deaths
Open Label - Everolimus 10mg
Serious events: 108 serious events
Other events: 218 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Everolimus 10mg/Day
n=204 participants at risk
Afinitor DB: Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 participants at risk
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
Open Label - Everolimus 10mg
n=225 participants at risk
Afinitor OL (for data collected in the open-label period of the study): The open-label set included only patients who received at least one dose of open-label everolimus 10 mg and had at least one safety assessment during the open-label period of the study.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
3.4%
7/204
|
1.5%
3/203
|
1.3%
3/225
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Blood and lymphatic system disorders
Microcytic anaemia
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Cardiac arrest
|
0.98%
2/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Cardiac failure
|
0.98%
2/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Cardiac disorders
Cardiac failure congestive
|
0.98%
2/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Coronary artery stenosis
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Myocardial infarction
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Myocarditis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Cardiac disorders
Palpitations
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Cardiac disorders
Right ventricular dysfunction
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Cardiac disorders
Right ventricular failure
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/204
|
0.00%
0/203
|
1.3%
3/225
|
|
Cardiac disorders
Tricuspid valve incompetence
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Congenital, familial and genetic disorders
Branchial cyst
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Ear and labyrinth disorders
Deafness
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Endocrine disorders
Hypercalcaemia of malignancy
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Eye disorders
Cataract
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Eye disorders
Macular fibrosis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Eye disorders
Ophthalmoplegia
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Abdominal hernia obstructive
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Abdominal pain
|
2.9%
6/204
|
2.5%
5/203
|
5.8%
13/225
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.98%
2/204
|
0.99%
2/203
|
1.3%
3/225
|
|
Gastrointestinal disorders
Abdominal rigidity
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Ascites
|
1.5%
3/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Colitis
|
0.98%
2/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Diarrhoea
|
2.5%
5/204
|
0.99%
2/203
|
1.3%
3/225
|
|
Gastrointestinal disorders
Duodenal stenosis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/204
|
0.00%
0/203
|
0.89%
2/225
|
|
Gastrointestinal disorders
Gastritis erosive
|
0.49%
1/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.49%
1/204
|
0.99%
2/203
|
2.2%
5/225
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Haematemesis
|
0.49%
1/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Ileus
|
0.49%
1/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Intestinal dilatation
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Nausea
|
1.5%
3/204
|
2.0%
4/203
|
3.1%
7/225
|
|
Gastrointestinal disorders
Oesophageal haemorrhage
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Oesophageal stenosis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
0.49%
1/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Pancreatitis
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Peptic ulcer haemorrhage
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/204
|
0.99%
2/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Small intestinal haemorrhage
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Stomatitis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Swollen tongue
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Tongue oedema
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.98%
2/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Gastrointestinal disorders
Vomiting
|
0.98%
2/204
|
2.0%
4/203
|
4.4%
10/225
|
|
General disorders
Asthenia
|
2.5%
5/204
|
0.99%
2/203
|
2.7%
6/225
|
|
General disorders
Chest pain
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
General disorders
Chills
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
General disorders
Death
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
General disorders
Device occlusion
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
General disorders
Fatigue
|
0.00%
0/204
|
0.99%
2/203
|
0.44%
1/225
|
|
General disorders
General physical health deterioration
|
0.49%
1/204
|
0.49%
1/203
|
1.3%
3/225
|
|
General disorders
Generalised oedema
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
General disorders
Influenza like illness
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
General disorders
Malaise
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
General disorders
Multi-organ failure
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
General disorders
Oedema
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
General disorders
Oedema peripheral
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
General disorders
Performance status decreased
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
General disorders
Pyrexia
|
3.9%
8/204
|
1.5%
3/203
|
3.6%
8/225
|
|
General disorders
Sudden death
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
General disorders
Thrombosis in device
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/204
|
0.49%
1/203
|
0.89%
2/225
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Hepatobiliary disorders
Cholangitis
|
0.98%
2/204
|
0.00%
0/203
|
2.2%
5/225
|
|
Hepatobiliary disorders
Cholangitis acute
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Hepatobiliary disorders
Cholestasis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Hepatobiliary disorders
Hepatic failure
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Hepatobiliary disorders
Hepatic necrosis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.49%
1/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Hepatobiliary disorders
Jaundice
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Immune system disorders
Anaphylactic shock
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Immune system disorders
Drug hypersensitivity
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Infections and infestations
Arthritis bacterial
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Atypical pneumonia
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Bacteraemia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Bacterial infection
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Biliary tract infection
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Campylobacter infection
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Cellulitis
|
0.00%
0/204
|
0.00%
0/203
|
1.3%
3/225
|
|
Infections and infestations
Cholecystitis infective
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Infections and infestations
Cystitis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Enterococcal bacteraemia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Escherichia sepsis
|
0.98%
2/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Gastroenteritis
|
0.98%
2/204
|
0.99%
2/203
|
0.89%
2/225
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Infection
|
1.5%
3/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Liver abscess
|
0.49%
1/204
|
0.00%
0/203
|
0.89%
2/225
|
|
Infections and infestations
Lobar pneumonia
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Lung infection
|
0.00%
0/204
|
0.00%
0/203
|
0.89%
2/225
|
|
Infections and infestations
Perihepatic abscess
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Infections and infestations
Pilonidal cyst
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Pneumonia
|
1.5%
3/204
|
0.99%
2/203
|
4.4%
10/225
|
|
Infections and infestations
Pneumonia mycoplasmal
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Post procedural infection
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Sepsis
|
0.00%
0/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Infections and infestations
Septic shock
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Sinusitis
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Infections and infestations
Staphylococcal sepsis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Streptococcal sepsis
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Infections and infestations
Subcutaneous abscess
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/204
|
0.00%
0/203
|
0.89%
2/225
|
|
Infections and infestations
Viral infection
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Infections and infestations
Wound infection staphylococcal
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
Wound complication
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Injury, poisoning and procedural complications
Wound secretion
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Investigations
Alanine aminotransferase increased
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Investigations
Ammonia increased
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Investigations
Aspartate aminotransferase increased
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Investigations
Blood creatinine increased
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Investigations
Blood potassium decreased
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Investigations
C-reactive protein increased
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Investigations
Haemoglobin decreased
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Investigations
Weight decreased
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.98%
2/204
|
0.00%
0/203
|
1.3%
3/225
|
|
Metabolism and nutrition disorders
Dehydration
|
2.5%
5/204
|
0.99%
2/203
|
0.89%
2/225
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.49%
1/204
|
0.49%
1/203
|
1.3%
3/225
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/204
|
0.00%
0/203
|
0.89%
2/225
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.98%
2/204
|
1.5%
3/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.98%
2/204
|
0.99%
2/203
|
1.3%
3/225
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.49%
1/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/204
|
0.49%
1/203
|
1.8%
4/225
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Metabolism and nutrition disorders
Hypophagia
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Metabolism and nutrition disorders
Polydipsia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.49%
1/204
|
0.99%
2/203
|
0.89%
2/225
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/204
|
0.99%
2/203
|
0.00%
0/225
|
|
Musculoskeletal and connective tissue disorders
Polyarthritis
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/204
|
0.99%
2/203
|
0.00%
0/225
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrinoma
|
0.00%
0/204
|
0.00%
0/203
|
0.89%
2/225
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine tumour
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic neuroendocrine tumour metastatic
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Nervous system disorders
Ataxia
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Nervous system disorders
Cerebrovascular accident
|
0.49%
1/204
|
0.00%
0/203
|
1.3%
3/225
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/204
|
0.99%
2/203
|
0.44%
1/225
|
|
Nervous system disorders
Dizziness
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Nervous system disorders
Epiduritis
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.49%
1/204
|
0.00%
0/203
|
0.89%
2/225
|
|
Nervous system disorders
Hypoglycaemic coma
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Nervous system disorders
Mental impairment
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Nervous system disorders
Sciatica
|
0.49%
1/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Nervous system disorders
Syncope
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Nervous system disorders
Tremor
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Nervous system disorders
Unresponsive to stimuli
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Psychiatric disorders
Confusional state
|
1.5%
3/204
|
1.5%
3/203
|
0.89%
2/225
|
|
Psychiatric disorders
Listless
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Psychiatric disorders
Mental status changes
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Calculus urinary
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Haematuria
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Polyuria
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Pyelocaliectasis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Renal colic
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Renal failure
|
1.5%
3/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Renal and urinary disorders
Renal failure acute
|
0.98%
2/204
|
1.5%
3/203
|
1.8%
4/225
|
|
Renal and urinary disorders
Renal impairment
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Renal and urinary disorders
Renal tubular necrosis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.49%
1/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.98%
2/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.9%
6/204
|
0.99%
2/203
|
0.89%
2/225
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.49%
1/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
1.5%
3/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
Nasal obstruction
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.98%
2/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
3.4%
7/204
|
0.00%
0/203
|
0.89%
2/225
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.5%
5/204
|
0.49%
1/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary hypertension
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.98%
2/204
|
0.49%
1/203
|
0.89%
2/225
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Skin and subcutaneous tissue disorders
Stasis dermatitis
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Vascular disorders
Aneurysm ruptured
|
0.00%
0/204
|
0.00%
0/203
|
0.44%
1/225
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/204
|
0.49%
1/203
|
0.00%
0/225
|
|
Vascular disorders
Hypotension
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
|
Vascular disorders
Venous thrombosis
|
0.49%
1/204
|
0.00%
0/203
|
0.00%
0/225
|
Other adverse events
| Measure |
Everolimus 10mg/Day
n=204 participants at risk
Afinitor DB: Participants received 10 mg per day of everolimus plus best supportive care. Patients received their first dose of everolimus at Visit 2 (Cycle 1 Day 1).
|
Placebo
n=203 participants at risk
Participants received matching placebo to everolimus daily plus best supportive care. Patients received their first dose of matching placebo at Visit 2 (Cycle 1 Day 1).
|
Open Label - Everolimus 10mg
n=225 participants at risk
Afinitor OL (for data collected in the open-label period of the study): The open-label set included only patients who received at least one dose of open-label everolimus 10 mg and had at least one safety assessment during the open-label period of the study.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
23.5%
48/204
|
8.9%
18/203
|
24.4%
55/225
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.9%
12/204
|
2.0%
4/203
|
4.0%
9/225
|
|
Blood and lymphatic system disorders
Lymphopenia
|
7.4%
15/204
|
3.0%
6/203
|
4.4%
10/225
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.9%
14/204
|
2.0%
4/203
|
10.7%
24/225
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
14.2%
29/204
|
0.99%
2/203
|
8.9%
20/225
|
|
Gastrointestinal disorders
Abdominal distension
|
8.8%
18/204
|
6.9%
14/203
|
8.4%
19/225
|
|
Gastrointestinal disorders
Abdominal pain
|
23.0%
47/204
|
23.6%
48/203
|
24.4%
55/225
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.7%
30/204
|
7.4%
15/203
|
12.9%
29/225
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
12.3%
25/204
|
3.9%
8/203
|
9.8%
22/225
|
|
Gastrointestinal disorders
Ascites
|
6.4%
13/204
|
2.0%
4/203
|
3.1%
7/225
|
|
Gastrointestinal disorders
Constipation
|
14.7%
30/204
|
12.8%
26/203
|
14.2%
32/225
|
|
Gastrointestinal disorders
Diarrhoea
|
47.5%
97/204
|
23.2%
47/203
|
42.7%
96/225
|
|
Gastrointestinal disorders
Dry mouth
|
11.3%
23/204
|
4.4%
9/203
|
3.6%
8/225
|
|
Gastrointestinal disorders
Dyspepsia
|
6.4%
13/204
|
6.4%
13/203
|
3.6%
8/225
|
|
Gastrointestinal disorders
Flatulence
|
4.9%
10/204
|
3.9%
8/203
|
6.2%
14/225
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
2.5%
5/204
|
3.0%
6/203
|
5.8%
13/225
|
|
Gastrointestinal disorders
Haemorrhoids
|
2.9%
6/204
|
2.0%
4/203
|
7.6%
17/225
|
|
Gastrointestinal disorders
Mouth ulceration
|
6.9%
14/204
|
2.0%
4/203
|
6.7%
15/225
|
|
Gastrointestinal disorders
Nausea
|
32.4%
66/204
|
31.5%
64/203
|
35.6%
80/225
|
|
Gastrointestinal disorders
Stomatitis
|
53.9%
110/204
|
13.3%
27/203
|
46.7%
105/225
|
|
Gastrointestinal disorders
Toothache
|
5.4%
11/204
|
2.5%
5/203
|
4.4%
10/225
|
|
Gastrointestinal disorders
Vomiting
|
29.9%
61/204
|
20.2%
41/203
|
31.1%
70/225
|
|
General disorders
Asthenia
|
17.2%
35/204
|
19.7%
40/203
|
18.2%
41/225
|
|
General disorders
Chills
|
5.4%
11/204
|
0.49%
1/203
|
6.2%
14/225
|
|
General disorders
Fatigue
|
44.6%
91/204
|
26.1%
53/203
|
32.4%
73/225
|
|
General disorders
Influenza like illness
|
4.4%
9/204
|
1.5%
3/203
|
7.1%
16/225
|
|
General disorders
Oedema peripheral
|
37.3%
76/204
|
11.3%
23/203
|
29.3%
66/225
|
|
General disorders
Pyrexia
|
27.5%
56/204
|
11.3%
23/203
|
25.3%
57/225
|
|
Infections and infestations
Bronchitis
|
2.0%
4/204
|
1.5%
3/203
|
6.7%
15/225
|
|
Infections and infestations
Influenza
|
2.9%
6/204
|
3.4%
7/203
|
5.3%
12/225
|
|
Infections and infestations
Nasopharyngitis
|
16.2%
33/204
|
6.9%
14/203
|
16.9%
38/225
|
|
Infections and infestations
Pneumonia
|
5.4%
11/204
|
0.00%
0/203
|
5.8%
13/225
|
|
Infections and infestations
Sinusitis
|
6.9%
14/204
|
2.0%
4/203
|
7.6%
17/225
|
|
Infections and infestations
Upper respiratory tract infection
|
7.8%
16/204
|
3.4%
7/203
|
12.4%
28/225
|
|
Infections and infestations
Urinary tract infection
|
11.3%
23/204
|
5.4%
11/203
|
10.2%
23/225
|
|
Investigations
Alanine aminotransferase increased
|
4.9%
10/204
|
4.4%
9/203
|
7.6%
17/225
|
|
Investigations
Aspartate aminotransferase increased
|
5.9%
12/204
|
5.4%
11/203
|
12.4%
28/225
|
|
Investigations
Blood alkaline phosphatase increased
|
5.9%
12/204
|
5.4%
11/203
|
11.1%
25/225
|
|
Investigations
Blood creatinine increased
|
4.9%
10/204
|
2.0%
4/203
|
6.7%
15/225
|
|
Investigations
Haemoglobin decreased
|
7.4%
15/204
|
0.99%
2/203
|
7.1%
16/225
|
|
Investigations
Weight decreased
|
28.4%
58/204
|
11.8%
24/203
|
32.0%
72/225
|
|
Metabolism and nutrition disorders
Decreased appetite
|
28.9%
59/204
|
18.2%
37/203
|
28.4%
64/225
|
|
Metabolism and nutrition disorders
Dehydration
|
4.9%
10/204
|
3.4%
7/203
|
9.8%
22/225
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
9.8%
20/204
|
0.00%
0/203
|
9.3%
21/225
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
12.7%
26/204
|
0.99%
2/203
|
7.1%
16/225
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
19.6%
40/204
|
10.3%
21/203
|
25.8%
58/225
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
7.8%
16/204
|
0.99%
2/203
|
4.4%
10/225
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
5.4%
11/204
|
3.4%
7/203
|
4.4%
10/225
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.3%
17/204
|
2.5%
5/203
|
4.9%
11/225
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
9.8%
20/204
|
1.5%
3/203
|
9.3%
21/225
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
15.2%
31/204
|
6.9%
14/203
|
15.1%
34/225
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.2%
31/204
|
10.8%
22/203
|
17.8%
40/225
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.3%
21/204
|
3.9%
8/203
|
6.7%
15/225
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
5.9%
12/204
|
2.0%
4/203
|
6.7%
15/225
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
5.9%
12/204
|
4.4%
9/203
|
7.6%
17/225
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
7.4%
15/204
|
6.9%
14/203
|
7.6%
17/225
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.2%
29/204
|
4.9%
10/203
|
9.8%
22/225
|
|
Nervous system disorders
Dizziness
|
11.8%
24/204
|
7.9%
16/203
|
8.0%
18/225
|
|
Nervous system disorders
Dysgeusia
|
18.6%
38/204
|
5.4%
11/203
|
20.4%
46/225
|
|
Nervous system disorders
Headache
|
30.4%
62/204
|
14.8%
30/203
|
23.1%
52/225
|
|
Psychiatric disorders
Depression
|
6.9%
14/204
|
1.5%
3/203
|
8.0%
18/225
|
|
Psychiatric disorders
Insomnia
|
13.7%
28/204
|
8.4%
17/203
|
12.0%
27/225
|
|
Renal and urinary disorders
Proteinuria
|
4.9%
10/204
|
0.99%
2/203
|
5.8%
13/225
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.1%
45/204
|
10.3%
21/203
|
24.0%
54/225
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.2%
33/204
|
6.4%
13/203
|
15.1%
34/225
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
21.6%
44/204
|
1.5%
3/203
|
16.9%
38/225
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
11.3%
23/204
|
5.9%
12/203
|
12.9%
29/225
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.9%
12/204
|
0.99%
2/203
|
2.7%
6/225
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
10.3%
21/204
|
0.00%
0/203
|
7.6%
17/225
|
|
Skin and subcutaneous tissue disorders
Acne
|
6.4%
13/204
|
2.5%
5/203
|
6.7%
15/225
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
3.9%
8/204
|
4.4%
9/203
|
5.3%
12/225
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
4.4%
9/204
|
0.99%
2/203
|
5.8%
13/225
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
12.7%
26/204
|
5.9%
12/203
|
12.4%
28/225
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.4%
11/204
|
1.5%
3/203
|
1.8%
4/225
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
13.7%
28/204
|
0.99%
2/203
|
11.6%
26/225
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
6.9%
14/204
|
0.99%
2/203
|
5.3%
12/225
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
19.6%
40/204
|
12.8%
26/203
|
18.7%
42/225
|
|
Skin and subcutaneous tissue disorders
Rash
|
52.5%
107/204
|
15.8%
32/203
|
40.0%
90/225
|
|
Vascular disorders
Flushing
|
2.0%
4/204
|
3.0%
6/203
|
5.3%
12/225
|
|
Vascular disorders
Hypertension
|
11.8%
24/204
|
4.4%
9/203
|
12.9%
29/225
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER