Trial Outcomes & Findings for Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor) (NCT NCT00093964)
NCT ID: NCT00093964
Last Updated: 2019-04-16
Results Overview
Progression-free survival was defined as subjects who survived greater than or equal to (\>=) 180 days without disease progression. Disease progression was assessed as per independent central blinded radiology assessment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
81 participants
Primary outcome timeframe
Month 6
Results posted on
2019-04-16
Participant Flow
First/Last subject in: 13 October 2004/28 October 2005. Data analysis cut-off: 21 October 2010
Participant milestones
| Measure |
Cilengitide 500 Milligram (mg)
Subjects received 1-hour intravenous infusion of 500 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
Subjects received 1-hour intravenous infusion of 2000 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Overall Study
STARTED
|
41
|
40
|
|
Overall Study
COMPLETED
|
41
|
40
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor)
Baseline characteristics by cohort
| Measure |
Cilengitide 500 Milligrams (mg)
n=41 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Total
n=81 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
53.0 years
STANDARD_DEVIATION 12.11 • n=5 Participants
|
54.6 years
STANDARD_DEVIATION 11.4 • n=7 Participants
|
53.8 years
STANDARD_DEVIATION 11.59 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Month 6Population: The intention-to-treat (ITT) population included all randomized subjects who had received at least 1 intravenous administration of cilengitide. Here,"Number of participants analyzed" signifies those subjects who were evaluable for this outcome measure.
Progression-free survival was defined as subjects who survived greater than or equal to (\>=) 180 days without disease progression. Disease progression was assessed as per independent central blinded radiology assessment.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Percentage of Subjects With Progression-free Survival
|
7.5 percentage of subjects
Interval 1.6 to 20.4
|
15.0 percentage of subjects
Interval 5.7 to 29.8
|
SECONDARY outcome
Timeframe: From the start of treatment up to 6 yearsPopulation: ITT population included all randomized subjects who had received at least 1 intravenous administration of cilengitide. Here,"Number of participants analysed" signifies those subjects who were evaluable for this outcome measure.
Overall response rate was defined as percentage of subjects who had best response during the study which was either complete response (CR: disappearance of all tumors, no new lesions and stable or improved neurological examination) or partial response (PR: \>= reduction in the sum of the products of the largest perpendicular diameters compared to the baseline sum, no worsening of evaluable lesion and stable or improved neurological examination). CR or PR was confirmed within 31 days with a repeat neuroimaging.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Percentage of Subjects With Overall Response Rate
|
5.0 percentage of subjects
Interval 0.6 to 16.9
|
12.5 percentage of subjects
Interval 4.2 to 26.8
|
SECONDARY outcome
Timeframe: From the start of treatment until disease progression (assessed up to a maximum of 6 years)Population: ITT population included all randomized subjects who had received at least 1 intravenous administration of cilengitide.
Time to disease progression was defined as the number of days between the first dose and the date of first assessment of progressive disease during the study or until death. Surviving subjects without progressive disease were censored at the time of the last visit and the subject was known to be non-progressing. Disease progression was assessed as per independent central blinded radiology assessment.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=41 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Time to Disease Progression
|
1.81 months
Interval 0.39 to 56.71
|
1.91 months
Interval 0.66 to 57.76
|
SECONDARY outcome
Timeframe: From the start of treatment until death (assessed up to a maximum of 6 years)Population: ITT population included all randomized subjects who had received at least 1 intravenous administration of cilengitide.
Survival time was defined as the number of months between the date of randomization and the date of death or the last date the subject was known to be alive.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=41 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Overall Survival Time
|
6.54 months
Interval 1.45 to 65.92
|
9.91 months
Interval 0.92 to 67.23
|
SECONDARY outcome
Timeframe: From the start of treatment up to 1 yearPopulation: ITT population included all randomized subjects who had received at least 1 intravenous administration of cilengitide.
1-year survival rate was defined as percentage of subjects who survived for \>=365 days with or without disease progression. Disease progression was assessed as per independent central blinded radiology assessment.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=41 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Percentage of Subjects With 1-year of Survival Rate
|
22.0 percentage of subjects
Interval 10.9 to 35.5
|
37.5 percentage of subjects
Interval 22.9 to 52.1
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2Population: The pharmacokinetic (PK) population: subjects who had received cilengitide and who had blood samples drawn in Week 1 that provided drug concentration for non-compartmental PK evaluation. Here,"Overall Number of participants analyzed" = subjects evaluable for this outcome and "Number analyzed" = subjects evaluable for the specified category.
Cmax is the maximum observed plasma concentration of cilengitide after administration.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax)
Cycle 1
|
40.4 microgram per milliliter (mcg/mL)
Standard Deviation 24.4
|
105.7 microgram per milliliter (mcg/mL)
Standard Deviation 14.1
|
|
Maximum Observed Plasma Concentration (Cmax)
Cycle 2
|
35.4 microgram per milliliter (mcg/mL)
Standard Deviation 20.6
|
169.7 microgram per milliliter (mcg/mL)
Standard Deviation 20.7
|
SECONDARY outcome
Timeframe: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2Population: The PK population: subjects who had received cilengitide and who had blood samples drawn in Week 1 that provided drug concentration for non-compartmental PK evaluation. Here,"Overall Number of participants analyzed" = subjects evaluable for this outcome and "Number analyzed" = subjects evaluable for the specified category.
Tmax is the time to reach the maximum plasma concentration (Cmax) of cilengitide.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax)
Cycle 1
|
1.13 Hour (h)
Interval 1.08 to 1.17
|
1.33 Hour (h)
Interval 1.08 to 1.5
|
|
Time to Reach Maximum Plasma Concentration (Tmax)
Cycle 2
|
1.17 Hour (h)
Interval 1.08 to 1.25
|
1.00 Hour (h)
Interval 1.0 to 1.08
|
SECONDARY outcome
Timeframe: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2Population: The PK population: subjects who had received cilengitide and who had blood samples drawn in Week 1 that provided drug concentration for non-compartmental PK evaluation. Here,"Overall Number of participants analyzed" = subjects evaluable for this outcome and "Number analyzed" = subjects evaluable for the specified category.
AUC 0-infinity is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration of cilengitide.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity After Administration (AUC 0-infinity)
Cycle 1
|
92.7 Microgram per milliliter*hour (mcg/mL*h)
Standard Deviation 60.4
|
346.5 Microgram per milliliter*hour (mcg/mL*h)
Standard Deviation 50.3
|
|
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity After Administration (AUC 0-infinity)
Cycle 2
|
84.6 Microgram per milliliter*hour (mcg/mL*h)
Standard Deviation 33.2
|
429.3 Microgram per milliliter*hour (mcg/mL*h)
Standard Deviation 27.4
|
SECONDARY outcome
Timeframe: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2Population: The PK population: subjects who had received cilengitide and who had blood samples drawn in Week 1 that provided drug concentration for non-compartmental PK evaluation. Here,"Overall Number of participants analyzed" = subjects evaluable for this outcome and "Number analyzed" = subjects evaluable for the specified category.
Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Apparent Terminal Rate Constant (Lambda z)
Cycle 1
|
0.320 Per hour (/h)
Standard Deviation 0.080
|
0.204 Per hour (/h)
Standard Deviation 0.010
|
|
Apparent Terminal Rate Constant (Lambda z)
Cycle 2
|
0.325 Per hour (/h)
Standard Deviation 0.107
|
0.211 Per hour (/h)
Standard Deviation 0.008
|
SECONDARY outcome
Timeframe: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2Population: The PK population: subjects who had received cilengitide and who had blood samples drawn in Week 1 that provided drug concentration for non-compartmental PK evaluation. Here,"Overall Number of participants analyzed" = subjects evaluable for this outcome and "Number analyzed" = subjects evaluable for the specified category.
The t1/2 is the time taken to eliminate half the amount of cilengitide.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Terminal Half-life (t1/2)
Cycle 1
|
2.24 Hour (h)
Interval 1.84 to 2.63
|
3.38 Hour (h)
Interval 3.24 to 3.59
|
|
Terminal Half-life (t1/2)
Cycle 2
|
2.04 Hour (h)
Interval 1.63 to 3.28
|
3.21 Hour (h)
Interval 3.21 to 3.42
|
SECONDARY outcome
Timeframe: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2Population: The pharmacokinetic (PK) population: subjects who had received cilengitide and who had blood samples drawn in Week 1 that provided drug concentration for non-compartmental PK evaluation. Here,"Overall Number of participants analyzed" = subjects evaluable for this outcome and "Number analyzed" = subjects evaluable for the specified category.
MRT is defined as the mean duration of time a drug molecule is present in the systemic circulation.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Mean Residence Time of Drug in the Body (MRT)
Cycle 1
|
2.76 Hour (h)
Standard Deviation 0.66
|
3.98 Hour (h)
Standard Deviation 0.25
|
|
Mean Residence Time of Drug in the Body (MRT)
Cycle 2
|
2.92 Hour (h)
Standard Deviation 0.74
|
3.42 Hour (h)
Standard Deviation 0.18
|
SECONDARY outcome
Timeframe: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2Population: The pharmacokinetic (PK) population: subjects who had received cilengitide and who had blood samples drawn in Week 1 that provided drug concentration for non-compartmental PK evaluation. Here,"Overall Number of participants analyzed" = subjects evaluable for this outcome and "Number analyzed" = subjects evaluable for the specified category.
CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as dose divided by AUC0-infinity.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Total Body Clearance (CL) of Drug From Plasma/Cerebro Spinal Fluid (CSF)
Cycle 1
|
6.85 Liter per hour (L/h)
Standard Deviation 4.47
|
5.85 Liter per hour (L/h)
Standard Deviation 0.86
|
|
Total Body Clearance (CL) of Drug From Plasma/Cerebro Spinal Fluid (CSF)
Cycle 2
|
6.75 Liter per hour (L/h)
Standard Deviation 3.25
|
4.67 Liter per hour (L/h)
Standard Deviation 0.31
|
SECONDARY outcome
Timeframe: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2Population: The PK population included the subjects who had received cilengitide and who had had blood samples drawn in Week 1 and/or 5 that provided drug concentration for non-compartmental PK evaluation. Here, "Number of participants analysed" signifies those subjects who were evaluable for this outcome measure.
Vz was calculated as Dose/(AUC0-infinity multiplied by elimination rate constant \[lambda z\]) following single dose.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase (Vz)
Cycle 1
|
20.3 Liter (L)
Standard Deviation 8.9
|
28.9 Liter (L)
Standard Deviation 5.5
|
|
Apparent Volume of Distribution During the Terminal Phase (Vz)
Cycle 2
|
21.0 Liter (L)
Standard Deviation 6.8
|
22.1 Liter (L)
Standard Deviation 1.2
|
SECONDARY outcome
Timeframe: Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2Population: The PK population included the subjects who had received cilengitide and who had blood samples drawn in Week 1 and/or 5 that provided drug concentration for non-compartmental PK evaluation. Here, "Number of participants analysed" signifies those subjects who were evaluable for this outcome measure.
Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=5 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=6 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Apparent Volume of Distribution at Steady State (Vss)
Cycle 1
|
17.4 Liter (L)
Standard Deviation 7.8
|
23.3 Liter (L)
Standard Deviation 4.1
|
|
Apparent Volume of Distribution at Steady State (Vss)
Cycle 2
|
19.3 Liter (L)
Standard Deviation 8.3
|
15.9 Liter (L)
Standard Deviation 0.9
|
SECONDARY outcome
Timeframe: From the start of treatment up to 6 yearsPopulation: The safety population included all randomized subjects who had received at least 1 intravenous administration of cilengitide.
An AE was any untoward medical occurrence in a subject which did not necessarily have a causal relationship with the study drug. A TEAE was any AE that started on or any time after the day of first dose of cilengitide during the treatment phase or within the safety follow-up after last dose of cilengitide. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly.
Outcome measures
| Measure |
Cilengitide 500 Milligrams (mg)
n=41 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 500 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 Participants
Subjects received a 1-hour intravenous (i.v.) infusion of 2000 mg cilengitide twice weekly on Days 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs
|
41 subjects
|
39 subjects
|
|
Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs
|
16 subjects
|
18 subjects
|
Adverse Events
Cilengitide 500 Milligram (mg)
Serious events: 16 serious events
Other events: 41 other events
Deaths: 0 deaths
Cilengitide 2000 mg
Serious events: 18 serious events
Other events: 39 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cilengitide 500 Milligram (mg)
n=41 participants at risk
Subjects received 1-hour intravenous infusion of 500 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 participants at risk
Subjects received 1-hour intravenous infusion of 2000 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/41
|
2.5%
1/40
|
|
Cardiac disorders
Atrial fibrillation
|
2.4%
1/41
|
2.5%
1/40
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.00%
0/41
|
2.5%
1/40
|
|
Eye disorders
Diplopia
|
0.00%
0/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Nausea
|
2.4%
1/41
|
0.00%
0/40
|
|
Gastrointestinal disorders
Splenic artery aneurysm
|
2.4%
1/41
|
0.00%
0/40
|
|
Gastrointestinal disorders
Vomiting
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Asthenia
|
4.9%
2/41
|
2.5%
1/40
|
|
General disorders
Chest pain
|
0.00%
0/41
|
2.5%
1/40
|
|
General disorders
Fatigue
|
2.4%
1/41
|
2.5%
1/40
|
|
General disorders
Gait disturbance
|
0.00%
0/41
|
2.5%
1/40
|
|
General disorders
Generalised oedema
|
0.00%
0/41
|
2.5%
1/40
|
|
General disorders
Oedema peripheral
|
0.00%
0/41
|
2.5%
1/40
|
|
Infections and infestations
Aspergillosis
|
0.00%
0/41
|
2.5%
1/40
|
|
Infections and infestations
Brain abscess
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Cellulitis
|
2.4%
1/41
|
2.5%
1/40
|
|
Infections and infestations
Clostridium colitis
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Herpes zoster
|
2.4%
1/41
|
2.5%
1/40
|
|
Infections and infestations
Sepsis
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Blood glucose increased
|
0.00%
0/41
|
2.5%
1/40
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Amnesia
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Aphasia
|
4.9%
2/41
|
7.5%
3/40
|
|
Nervous system disorders
Ataxia
|
2.4%
1/41
|
2.5%
1/40
|
|
Nervous system disorders
Brain oedema
|
4.9%
2/41
|
0.00%
0/40
|
|
Nervous system disorders
Cerebral haemorrhage
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Convulsion
|
12.2%
5/41
|
20.0%
8/40
|
|
Nervous system disorders
Grand mal convulsion
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Headache
|
12.2%
5/41
|
5.0%
2/40
|
|
Nervous system disorders
Hemiparesis
|
2.4%
1/41
|
2.5%
1/40
|
|
Nervous system disorders
Hemiplegia
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Motor dysfunction
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Neurologic neglect syndrome
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Neuropathy
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Postictal paralysis
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Somnolence
|
2.4%
1/41
|
0.00%
0/40
|
|
Psychiatric disorders
Affective disorder
|
2.4%
1/41
|
0.00%
0/40
|
|
Psychiatric disorders
Confusional state
|
2.4%
1/41
|
0.00%
0/40
|
|
Psychiatric disorders
Mental status changes
|
4.9%
2/41
|
2.5%
1/40
|
|
Renal and urinary disorders
Renal failure
|
2.4%
1/41
|
0.00%
0/40
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
2.4%
1/41
|
2.5%
1/40
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/41
|
7.5%
3/40
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
2.4%
1/41
|
0.00%
0/40
|
|
Vascular disorders
Deep vein thrombosis
|
4.9%
2/41
|
5.0%
2/40
|
Other adverse events
| Measure |
Cilengitide 500 Milligram (mg)
n=41 participants at risk
Subjects received 1-hour intravenous infusion of 500 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
Cilengitide 2000 mg
n=40 participants at risk
Subjects received 1-hour intravenous infusion of 2000 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.
|
|---|---|---|
|
Blood and lymphatic system disorders
Haemoglobinaemia
|
2.4%
1/41
|
0.00%
0/40
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/41
|
2.5%
1/40
|
|
Blood and lymphatic system disorders
Lymphopenia
|
4.9%
2/41
|
5.0%
2/40
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.4%
1/41
|
2.5%
1/40
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
4.9%
2/41
|
2.5%
1/40
|
|
Ear and labyrinth disorders
Deafness
|
2.4%
1/41
|
0.00%
0/40
|
|
Ear and labyrinth disorders
Ear pain
|
4.9%
2/41
|
5.0%
2/40
|
|
Ear and labyrinth disorders
Middle ear effusion
|
2.4%
1/41
|
0.00%
0/40
|
|
Ear and labyrinth disorders
Otorrhoea
|
2.4%
1/41
|
0.00%
0/40
|
|
Ear and labyrinth disorders
Tinnitus
|
2.4%
1/41
|
2.5%
1/40
|
|
Ear and labyrinth disorders
Tympanic membrane perforation
|
0.00%
0/41
|
2.5%
1/40
|
|
Ear and labyrinth disorders
Vertigo
|
2.4%
1/41
|
0.00%
0/40
|
|
Endocrine disorders
Cushingoid
|
12.2%
5/41
|
7.5%
3/40
|
|
Endocrine disorders
Hirsutism
|
2.4%
1/41
|
0.00%
0/40
|
|
Eye disorders
Cataract
|
0.00%
0/41
|
2.5%
1/40
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/41
|
2.5%
1/40
|
|
Eye disorders
Conjunctivitis
|
2.4%
1/41
|
2.5%
1/40
|
|
Eye disorders
Diplopia
|
2.4%
1/41
|
5.0%
2/40
|
|
Eye disorders
Dry eye
|
2.4%
1/41
|
0.00%
0/40
|
|
Eye disorders
Eye irritation
|
2.4%
1/41
|
0.00%
0/40
|
|
Eye disorders
Eye pain
|
0.00%
0/41
|
2.5%
1/40
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/41
|
2.5%
1/40
|
|
Eye disorders
Gaze palsy
|
0.00%
0/41
|
2.5%
1/40
|
|
Eye disorders
Glaucoma
|
0.00%
0/41
|
2.5%
1/40
|
|
Eye disorders
Lacrimation increased
|
2.4%
1/41
|
0.00%
0/40
|
|
Eye disorders
Ophthalmoplegia
|
2.4%
1/41
|
0.00%
0/40
|
|
Eye disorders
Papilloedema
|
2.4%
1/41
|
2.5%
1/40
|
|
Eye disorders
Photophobia
|
2.4%
1/41
|
0.00%
0/40
|
|
Eye disorders
Scleral haemorrhage
|
2.4%
1/41
|
0.00%
0/40
|
|
Eye disorders
Vision blurred
|
12.2%
5/41
|
7.5%
3/40
|
|
Eye disorders
Visual acuity reduced
|
12.2%
5/41
|
2.5%
1/40
|
|
Eye disorders
Vitreous floaters
|
2.4%
1/41
|
0.00%
0/40
|
|
Gastrointestinal disorders
Abdominal distension
|
7.3%
3/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Abdominal pain
|
4.9%
2/41
|
7.5%
3/40
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.4%
1/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Chapped lips
|
0.00%
0/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Constipation
|
7.3%
3/41
|
10.0%
4/40
|
|
Gastrointestinal disorders
Diarrhoea
|
17.1%
7/41
|
12.5%
5/40
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Dyspepsia
|
7.3%
3/41
|
7.5%
3/40
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Faecal incontinence
|
2.4%
1/41
|
0.00%
0/40
|
|
Gastrointestinal disorders
Flatulence
|
7.3%
3/41
|
0.00%
0/40
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
2.4%
1/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Gingival hypertrophy
|
2.4%
1/41
|
0.00%
0/40
|
|
Gastrointestinal disorders
Gingivitis
|
0.00%
0/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Haematochezia
|
2.4%
1/41
|
0.00%
0/40
|
|
Gastrointestinal disorders
Haemorrhoids
|
2.4%
1/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Lip disorder
|
0.00%
0/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Lip dry
|
0.00%
0/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Loose stools
|
2.4%
1/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Nausea
|
24.4%
10/41
|
15.0%
6/40
|
|
Gastrointestinal disorders
Stomach discomfort
|
0.00%
0/41
|
2.5%
1/40
|
|
Gastrointestinal disorders
Toothache
|
2.4%
1/41
|
0.00%
0/40
|
|
Gastrointestinal disorders
Vomiting
|
7.3%
3/41
|
5.0%
2/40
|
|
General disorders
Abasia
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Adverse drug reaction
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Asthenia
|
2.4%
1/41
|
15.0%
6/40
|
|
General disorders
Catheter related complication
|
0.00%
0/41
|
2.5%
1/40
|
|
General disorders
Catheter site haemorrhage
|
4.9%
2/41
|
0.00%
0/40
|
|
General disorders
Catheter site oedema
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Catheter site pain
|
2.4%
1/41
|
5.0%
2/40
|
|
General disorders
Chest discomfort
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Chest pain
|
0.00%
0/41
|
2.5%
1/40
|
|
General disorders
Chills
|
2.4%
1/41
|
2.5%
1/40
|
|
General disorders
Cyst
|
0.00%
0/41
|
5.0%
2/40
|
|
General disorders
Difficulty in walking
|
2.4%
1/41
|
2.5%
1/40
|
|
General disorders
Facial pain
|
0.00%
0/41
|
2.5%
1/40
|
|
General disorders
Fatigue
|
26.8%
11/41
|
45.0%
18/40
|
|
General disorders
Gait disturbance
|
9.8%
4/41
|
15.0%
6/40
|
|
General disorders
Influenza like illness
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Infusion site pain
|
0.00%
0/41
|
2.5%
1/40
|
|
General disorders
Infusion site reaction
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Malaise
|
0.00%
0/41
|
2.5%
1/40
|
|
General disorders
Mucosal inflammation
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Oedema
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Oedema peripheral
|
29.3%
12/41
|
25.0%
10/40
|
|
General disorders
Pitting oedema
|
2.4%
1/41
|
0.00%
0/40
|
|
General disorders
Pyrexia
|
4.9%
2/41
|
7.5%
3/40
|
|
General disorders
Temperature intolerance
|
2.4%
1/41
|
2.5%
1/40
|
|
General disorders
Venipuncture site bruise
|
2.4%
1/41
|
0.00%
0/40
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/41
|
2.5%
1/40
|
|
Immune system disorders
Hypersensitivity
|
2.4%
1/41
|
2.5%
1/40
|
|
Immune system disorders
Seasonal allergy
|
4.9%
2/41
|
0.00%
0/40
|
|
Infections and infestations
Bacteriuria
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Body tinea
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Candidiasis
|
0.00%
0/41
|
5.0%
2/40
|
|
Infections and infestations
Cellulitis
|
2.4%
1/41
|
5.0%
2/40
|
|
Infections and infestations
Conjunctivitis infective
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Cystitis
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Dental caries
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Eczema infected
|
0.00%
0/41
|
2.5%
1/40
|
|
Infections and infestations
Escherichia urinary tract infection
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Eye infection
|
2.4%
1/41
|
2.5%
1/40
|
|
Infections and infestations
Folliculitis
|
0.00%
0/41
|
2.5%
1/40
|
|
Infections and infestations
Gastroenteritis
|
4.9%
2/41
|
0.00%
0/40
|
|
Infections and infestations
Herpes simplex
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Herpes zoster
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Hordeolum
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Influenza
|
0.00%
0/41
|
2.5%
1/40
|
|
Infections and infestations
Localised infection
|
0.00%
0/41
|
2.5%
1/40
|
|
Infections and infestations
Nasopharyngitis
|
4.9%
2/41
|
2.5%
1/40
|
|
Infections and infestations
Oral infection
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Otitis externa
|
0.00%
0/41
|
2.5%
1/40
|
|
Infections and infestations
Otitis media
|
0.00%
0/41
|
2.5%
1/40
|
|
Infections and infestations
Respiratory tract infection
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Rhinitis
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Sialoadenitis
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Sinusitis
|
7.3%
3/41
|
5.0%
2/40
|
|
Infections and infestations
Tooth abscess
|
2.4%
1/41
|
0.00%
0/40
|
|
Infections and infestations
Upper respiratory tract infection
|
12.2%
5/41
|
5.0%
2/40
|
|
Infections and infestations
Urinary tract infection
|
9.8%
4/41
|
7.5%
3/40
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/41
|
2.5%
1/40
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
2.4%
1/41
|
0.00%
0/40
|
|
Injury, poisoning and procedural complications
Back injury
|
0.00%
0/41
|
2.5%
1/40
|
|
Injury, poisoning and procedural complications
Blood blister
|
0.00%
0/41
|
2.5%
1/40
|
|
Injury, poisoning and procedural complications
Contusion
|
7.3%
3/41
|
7.5%
3/40
|
|
Injury, poisoning and procedural complications
Excoriation
|
4.9%
2/41
|
0.00%
0/40
|
|
Injury, poisoning and procedural complications
Fall
|
14.6%
6/41
|
7.5%
3/40
|
|
Injury, poisoning and procedural complications
Hand fracture
|
2.4%
1/41
|
0.00%
0/40
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.00%
0/41
|
2.5%
1/40
|
|
Injury, poisoning and procedural complications
Post procedural pain
|
2.4%
1/41
|
0.00%
0/40
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/41
|
2.5%
1/40
|
|
Injury, poisoning and procedural complications
Skin laceration
|
2.4%
1/41
|
7.5%
3/40
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/41
|
2.5%
1/40
|
|
Injury, poisoning and procedural complications
Tooth injury
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/41
|
2.5%
1/40
|
|
Investigations
Activated partial thromboplastin time shortened
|
0.00%
0/41
|
2.5%
1/40
|
|
Investigations
Alanine aminotransferase increased
|
4.9%
2/41
|
5.0%
2/40
|
|
Investigations
Anticonvulsant drug level increased
|
4.9%
2/41
|
2.5%
1/40
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/41
|
5.0%
2/40
|
|
Investigations
Bacteria urine
|
7.3%
3/41
|
0.00%
0/40
|
|
Investigations
Blood alkaline phosphatase increased
|
2.4%
1/41
|
2.5%
1/40
|
|
Investigations
Blood cholesterol increased
|
4.9%
2/41
|
2.5%
1/40
|
|
Investigations
Blood glucose increased
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Blood iron decreased
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Blood potassium decreased
|
0.00%
0/41
|
2.5%
1/40
|
|
Investigations
Blood urea increased
|
4.9%
2/41
|
0.00%
0/40
|
|
Investigations
Cardiac murmur
|
0.00%
0/41
|
2.5%
1/40
|
|
Investigations
Electrocardiogram ST segment elevation
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Electrocardiogram abnormal
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Haemoglobin decreased
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/41
|
2.5%
1/40
|
|
Investigations
Neutrophil count increased
|
4.9%
2/41
|
0.00%
0/40
|
|
Investigations
Nuclear magnetic resonance imaging abnormal
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Platelet count decreased
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Prothrombin time
|
0.00%
0/41
|
2.5%
1/40
|
|
Investigations
Red blood cell count decreased
|
2.4%
1/41
|
0.00%
0/40
|
|
Investigations
Tandem gait test abnormal
|
2.4%
1/41
|
2.5%
1/40
|
|
Investigations
Weight decreased
|
0.00%
0/41
|
2.5%
1/40
|
|
Investigations
Weight increased
|
2.4%
1/41
|
5.0%
2/40
|
|
Investigations
White blood cell count decreased
|
0.00%
0/41
|
2.5%
1/40
|
|
Investigations
White blood cells urine positive
|
4.9%
2/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Anorexia
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Dehydration
|
4.9%
2/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/41
|
2.5%
1/40
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/41
|
5.0%
2/40
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.4%
1/41
|
12.5%
5/40
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.8%
4/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.4%
1/41
|
2.5%
1/40
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Increased appetite
|
0.00%
0/41
|
2.5%
1/40
|
|
Metabolism and nutrition disorders
Markedly reduced dietary intake
|
2.4%
1/41
|
0.00%
0/40
|
|
Metabolism and nutrition disorders
Tetany
|
0.00%
0/41
|
2.5%
1/40
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
22.0%
9/41
|
5.0%
2/40
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
2.4%
1/41
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.8%
4/41
|
20.0%
8/40
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
2.4%
1/41
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
2.4%
1/41
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
2.4%
1/41
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
2.4%
1/41
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Muscle cramp
|
4.9%
2/41
|
7.5%
3/40
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/41
|
2.5%
1/40
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
12.2%
5/41
|
10.0%
4/40
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
2.4%
1/41
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
2.4%
1/41
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.9%
2/41
|
0.00%
0/40
|
|
Musculoskeletal and connective tissue disorders
Myopathy steroid
|
2.4%
1/41
|
2.5%
1/40
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/41
|
2.5%
1/40
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
7.3%
3/41
|
5.0%
2/40
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Amnesia
|
19.5%
8/41
|
12.5%
5/40
|
|
Nervous system disorders
Aphasia
|
12.2%
5/41
|
22.5%
9/40
|
|
Nervous system disorders
Ataxia
|
2.4%
1/41
|
7.5%
3/40
|
|
Nervous system disorders
Aura
|
4.9%
2/41
|
0.00%
0/40
|
|
Nervous system disorders
Balance disorder
|
17.1%
7/41
|
5.0%
2/40
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Cognitive disorder
|
4.9%
2/41
|
2.5%
1/40
|
|
Nervous system disorders
Convulsion
|
17.1%
7/41
|
10.0%
4/40
|
|
Nervous system disorders
Coordination abnormal
|
4.9%
2/41
|
2.5%
1/40
|
|
Nervous system disorders
Cranial nerve disorder
|
2.4%
1/41
|
5.0%
2/40
|
|
Nervous system disorders
Cranial neuropathy
|
7.3%
3/41
|
2.5%
1/40
|
|
Nervous system disorders
Disturbance in attention
|
7.3%
3/41
|
0.00%
0/40
|
|
Nervous system disorders
Dizziness
|
17.1%
7/41
|
17.5%
7/40
|
|
Nervous system disorders
Dysarthria
|
7.3%
3/41
|
2.5%
1/40
|
|
Nervous system disorders
Dysgeusia
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Dysgraphia
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Dyskinesia
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Dysphasia
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Facial palsy
|
2.4%
1/41
|
7.5%
3/40
|
|
Nervous system disorders
Facial paresis
|
12.2%
5/41
|
0.00%
0/40
|
|
Nervous system disorders
Grand mal convulsion
|
2.4%
1/41
|
2.5%
1/40
|
|
Nervous system disorders
Headache
|
34.1%
14/41
|
35.0%
14/40
|
|
Nervous system disorders
Hemianopia homonymous
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Hemiparesis
|
7.3%
3/41
|
10.0%
4/40
|
|
Nervous system disorders
Hemiplegia
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Hyperaesthesia
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Hyperreflexia
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Hypoaesthesia
|
4.9%
2/41
|
5.0%
2/40
|
|
Nervous system disorders
Lethargy
|
4.9%
2/41
|
2.5%
1/40
|
|
Nervous system disorders
Memory impairment
|
9.8%
4/41
|
12.5%
5/40
|
|
Nervous system disorders
Motor dysfunction
|
9.8%
4/41
|
5.0%
2/40
|
|
Nervous system disorders
Neurologic neglect syndrome
|
4.9%
2/41
|
2.5%
1/40
|
|
Nervous system disorders
Neuropathic pain
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Neuropathy
|
4.9%
2/41
|
0.00%
0/40
|
|
Nervous system disorders
Nystagmus
|
2.4%
1/41
|
5.0%
2/40
|
|
Nervous system disorders
Paraesthesia
|
4.9%
2/41
|
5.0%
2/40
|
|
Nervous system disorders
Partial seizures
|
2.4%
1/41
|
2.5%
1/40
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/41
|
7.5%
3/40
|
|
Nervous system disorders
Peroneal nerve palsy
|
0.00%
0/41
|
2.5%
1/40
|
|
Nervous system disorders
Pyramidal tract syndrome
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Reflex sympathetic dystrophy
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Sensory disturbance
|
2.4%
1/41
|
2.5%
1/40
|
|
Nervous system disorders
Simple partial seizures
|
2.4%
1/41
|
5.0%
2/40
|
|
Nervous system disorders
Sinus headache
|
2.4%
1/41
|
0.00%
0/40
|
|
Nervous system disorders
Somnolence
|
2.4%
1/41
|
5.0%
2/40
|
|
Nervous system disorders
Speech disorder
|
9.8%
4/41
|
7.5%
3/40
|
|
Nervous system disorders
Tremor
|
9.8%
4/41
|
10.0%
4/40
|
|
Nervous system disorders
Upper motor neurone lesion
|
4.9%
2/41
|
0.00%
0/40
|
|
Nervous system disorders
Visual field defect
|
2.4%
1/41
|
0.00%
0/40
|
|
Psychiatric disorders
Affect lability
|
2.4%
1/41
|
2.5%
1/40
|
|
Psychiatric disorders
Aggression
|
0.00%
0/41
|
2.5%
1/40
|
|
Psychiatric disorders
Agitation
|
4.9%
2/41
|
2.5%
1/40
|
|
Psychiatric disorders
Anxiety
|
4.9%
2/41
|
7.5%
3/40
|
|
Psychiatric disorders
Cognitive deterioration
|
0.00%
0/41
|
2.5%
1/40
|
|
Psychiatric disorders
Confusional state
|
19.5%
8/41
|
17.5%
7/40
|
|
Psychiatric disorders
Depression
|
7.3%
3/41
|
15.0%
6/40
|
|
Psychiatric disorders
Disorientation
|
0.00%
0/41
|
2.5%
1/40
|
|
Psychiatric disorders
Insomnia
|
9.8%
4/41
|
15.0%
6/40
|
|
Psychiatric disorders
Irritability
|
4.9%
2/41
|
0.00%
0/40
|
|
Psychiatric disorders
Mental status changes
|
2.4%
1/41
|
0.00%
0/40
|
|
Psychiatric disorders
Mood altered
|
4.9%
2/41
|
2.5%
1/40
|
|
Psychiatric disorders
Nervousness
|
2.4%
1/41
|
0.00%
0/40
|
|
Psychiatric disorders
Personality change
|
2.4%
1/41
|
5.0%
2/40
|
|
Psychiatric disorders
Psychomotor retardation
|
2.4%
1/41
|
0.00%
0/40
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/41
|
2.5%
1/40
|
|
Renal and urinary disorders
Haematuria
|
2.4%
1/41
|
2.5%
1/40
|
|
Renal and urinary disorders
Leukocyturia
|
2.4%
1/41
|
0.00%
0/40
|
|
Renal and urinary disorders
Micturition urgency
|
4.9%
2/41
|
2.5%
1/40
|
|
Renal and urinary disorders
Nephrolithiasis
|
2.4%
1/41
|
2.5%
1/40
|
|
Renal and urinary disorders
Pollakiuria
|
4.9%
2/41
|
0.00%
0/40
|
|
Renal and urinary disorders
Proteinuria
|
9.8%
4/41
|
0.00%
0/40
|
|
Renal and urinary disorders
Renal salt-wasting syndrome
|
0.00%
0/41
|
2.5%
1/40
|
|
Renal and urinary disorders
Urinary incontinence
|
9.8%
4/41
|
10.0%
4/40
|
|
Reproductive system and breast disorders
Breast pain
|
2.4%
1/41
|
0.00%
0/40
|
|
Reproductive system and breast disorders
Menstrual disorder
|
2.4%
1/41
|
0.00%
0/40
|
|
Reproductive system and breast disorders
Nipple pain
|
0.00%
0/41
|
2.5%
1/40
|
|
Reproductive system and breast disorders
Polymenorrhoea
|
2.4%
1/41
|
0.00%
0/40
|
|
Reproductive system and breast disorders
Prostatitis
|
2.4%
1/41
|
0.00%
0/40
|
|
Reproductive system and breast disorders
Sexual dysfunction
|
2.4%
1/41
|
5.0%
2/40
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.9%
2/41
|
10.0%
4/40
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.4%
1/41
|
12.5%
5/40
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
0.00%
0/41
|
2.5%
1/40
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/41
|
2.5%
1/40
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.9%
2/41
|
0.00%
0/40
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.00%
0/41
|
2.5%
1/40
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
4.9%
2/41
|
0.00%
0/40
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
2.4%
1/41
|
0.00%
0/40
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
2.4%
1/41
|
0.00%
0/40
|
|
Respiratory, thoracic and mediastinal disorders
Snoring
|
2.4%
1/41
|
0.00%
0/40
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.4%
1/41
|
0.00%
0/40
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
0.00%
0/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
2.4%
1/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.9%
2/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
4.9%
2/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Erythema
|
2.4%
1/41
|
0.00%
0/40
|
|
Skin and subcutaneous tissue disorders
Face oedema
|
0.00%
0/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
0.00%
0/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.9%
2/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.6%
6/41
|
17.5%
7/40
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
2.4%
1/41
|
0.00%
0/40
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
2.4%
1/41
|
0.00%
0/40
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
2.4%
1/41
|
0.00%
0/40
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/41
|
2.5%
1/40
|
|
Skin and subcutaneous tissue disorders
Skin fragility
|
0.00%
0/41
|
2.5%
1/40
|
|
Vascular disorders
Deep vein thrombosis
|
4.9%
2/41
|
0.00%
0/40
|
|
Vascular disorders
Hypertension
|
2.4%
1/41
|
0.00%
0/40
|
|
Vascular disorders
Hypotension
|
0.00%
0/41
|
5.0%
2/40
|
|
Vascular disorders
Petechiae
|
4.9%
2/41
|
2.5%
1/40
|
|
Vascular disorders
Phlebitis
|
0.00%
0/41
|
2.5%
1/40
|
|
Vascular disorders
Phlebitis superficial
|
0.00%
0/41
|
2.5%
1/40
|
Additional Information
Merck KGaA Communication Center
Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER