Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00093964
Recruitment Status : Completed
First Posted : October 11, 2004
Results First Posted : April 16, 2019
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
EMD Serono

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma Multiforme
Interventions Drug: Cilengitide 500 mg
Drug: Cilengitide 2000 mg
Enrollment 81
Recruitment Details First/Last subject in: 13 October 2004/28 October 2005. Data analysis cut-off: 21 October 2010
Pre-assignment Details  
Arm/Group Title Cilengitide 500 Milligram (mg) Cilengitide 2000 mg
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 41 40
Completed 41 40
Not Completed 0 0
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 41 40 81
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 40 participants 81 participants
53.0  (12.11) 54.6  (11.4) 53.8  (11.59)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 40 participants 81 participants
Female
18
  43.9%
12
  30.0%
30
  37.0%
Male
23
  56.1%
28
  70.0%
51
  63.0%
1.Primary Outcome
Title Percentage of Subjects With Progression-free Survival
Hide Description 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.
Time Frame Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 40 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
7.5
(1.6 to 20.4)
15.0
(5.7 to 29.8)
2.Secondary Outcome
Title Percentage of Subjects With Overall Response Rate
Hide Description 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.
Time Frame From the start of treatment up to 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 40 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
5.0
(0.6 to 16.9)
12.5
(4.2 to 26.8)
3.Secondary Outcome
Title Time to Disease Progression
Hide Description 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.
Time Frame From the start of treatment until disease progression (assessed up to a maximum of 6 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized subjects who had received at least 1 intravenous administration of cilengitide.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 41 40
Median (Full Range)
Unit of Measure: months
1.81
(0.39 to 56.71)
1.91
(0.66 to 57.76)
4.Secondary Outcome
Title Overall Survival Time
Hide Description 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.
Time Frame From the start of treatment until death (assessed up to a maximum of 6 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized subjects who had received at least 1 intravenous administration of cilengitide.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 41 40
Median (Full Range)
Unit of Measure: months
6.54
(1.45 to 65.92)
9.91
(0.92 to 67.23)
5.Secondary Outcome
Title Percentage of Subjects With 1-year of Survival Rate
Hide Description 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.
Time Frame From the start of treatment up to 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized subjects who had received at least 1 intravenous administration of cilengitide.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 41 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
22.0
(10.9 to 35.5)
37.5
(22.9 to 52.1)
6.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description Cmax is the maximum observed plasma concentration of cilengitide after administration.
Time Frame Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (mcg/mL)
Cycle 1 Number Analyzed 2 participants 3 participants
40.4  (24.4) 105.7  (14.1)
Cycle 2 Number Analyzed 3 participants 3 participants
35.4  (20.6) 169.7  (20.7)
7.Secondary Outcome
Title Time to Reach Maximum Plasma Concentration (Tmax)
Hide Description Tmax is the time to reach the maximum plasma concentration (Cmax) of cilengitide.
Time Frame Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Median (Full Range)
Unit of Measure: Hour (h)
Cycle 1 Number Analyzed 2 participants 3 participants
1.13
(1.08 to 1.17)
1.33
(1.08 to 1.50)
Cycle 2 Number Analyzed 3 participants 3 participants
1.17
(1.08 to 1.25)
1.00
(1.00 to 1.08)
8.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Infinity After Administration (AUC 0-infinity)
Hide Description 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.
Time Frame Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Mean (Standard Deviation)
Unit of Measure: Microgram per milliliter*hour (mcg/mL*h)
Cycle 1 Number Analyzed 2 participants 3 participants
92.7  (60.4) 346.5  (50.3)
Cycle 2 Number Analyzed 3 participants 3 participants
84.6  (33.2) 429.3  (27.4)
9.Secondary Outcome
Title Apparent Terminal Rate Constant (Lambda z)
Hide Description 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.
Time Frame Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Mean (Standard Deviation)
Unit of Measure: Per hour (/h)
Cycle 1 Number Analyzed 2 participants 3 participants
0.320  (0.080) 0.204  (0.010)
Cycle 2 Number Analyzed 3 participants 3 participants
0.325  (0.107) 0.211  (0.008)
10.Secondary Outcome
Title Terminal Half-life (t1/2)
Hide Description The t1/2 is the time taken to eliminate half the amount of cilengitide.
Time Frame Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Median (Full Range)
Unit of Measure: Hour (h)
Cycle 1 Number Analyzed 2 participants 3 participants
2.24
(1.84 to 2.63)
3.38
(3.24 to 3.59)
Cycle 2 Number Analyzed 3 participants 3 participants
2.04
(1.63 to 3.28)
3.21
(3.21 to 3.42)
11.Secondary Outcome
Title Mean Residence Time of Drug in the Body (MRT)
Hide Description MRT is defined as the mean duration of time a drug molecule is present in the systemic circulation.
Time Frame Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Mean (Standard Deviation)
Unit of Measure: Hour (h)
Cycle 1 Number Analyzed 2 participants 3 participants
2.76  (0.66) 3.98  (0.25)
Cycle 2 Number Analyzed 3 participants 3 participants
2.92  (0.74) 3.42  (0.18)
12.Secondary Outcome
Title Total Body Clearance (CL) of Drug From Plasma/Cerebro Spinal Fluid (CSF)
Hide Description 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.
Time Frame Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Mean (Standard Deviation)
Unit of Measure: Liter per hour (L/h)
Cycle 1 Number Analyzed 2 participants 3 participants
6.85  (4.47) 5.85  (0.86)
Cycle 2 Number Analyzed 3 participants 3 participants
6.75  (3.25) 4.67  (0.31)
13.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase (Vz)
Hide Description Vz was calculated as Dose/(AUC0-infinity multiplied by elimination rate constant [lambda z]) following single dose.
Time Frame Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Mean (Standard Deviation)
Unit of Measure: Liter (L)
Cycle 1 Number Analyzed 2 participants 3 participants
20.3  (8.9) 28.9  (5.5)
Cycle 2 Number Analyzed 3 participants 3 participants
21.0  (6.8) 22.1  (1.2)
14.Secondary Outcome
Title Apparent Volume of Distribution at Steady State (Vss)
Hide Description 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.
Time Frame Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cilengitide 500 Milligrams (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 5 6
Mean (Standard Deviation)
Unit of Measure: Liter (L)
Cycle 1 Number Analyzed 2 participants 3 participants
17.4  (7.8) 23.3  (4.1)
Cycle 2 Number Analyzed 3 participants 3 participants
19.3  (8.3) 15.9  (0.9)
15.Secondary Outcome
Title Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame From the start of treatment up to 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all randomized subjects who had received at least 1 intravenous administration of cilengitide.
Arm/Group Title Cilengitide 500 Milligram (mg) Cilengitide 2000 mg
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 41 40
Measure Type: Number
Unit of Measure: subjects
TEAEs 41 39
SAEs 16 18
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cilengitide 500 Milligram (mg) Cilengitide 2000 mg
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Cilengitide 500 Milligram (mg) Cilengitide 2000 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Cilengitide 500 Milligram (mg) Cilengitide 2000 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   16/41 (39.02%)   18/40 (45.00%) 
Blood and lymphatic system disorders     
Lymphopenia * 1  0/41 (0.00%)  1/40 (2.50%) 
Cardiac disorders     
Atrial fibrillation * 1  1/41 (2.44%)  1/40 (2.50%) 
Supraventricular tachycardia * 1  0/41 (0.00%)  1/40 (2.50%) 
Eye disorders     
Diplopia * 1  0/41 (0.00%)  1/40 (2.50%) 
Gastrointestinal disorders     
Nausea * 1  1/41 (2.44%)  0/40 (0.00%) 
Splenic artery aneurysm * 1  1/41 (2.44%)  0/40 (0.00%) 
Vomiting * 1  1/41 (2.44%)  0/40 (0.00%) 
General disorders     
Asthenia * 1  2/41 (4.88%)  1/40 (2.50%) 
Chest pain * 1  0/41 (0.00%)  1/40 (2.50%) 
Fatigue * 1  1/41 (2.44%)  1/40 (2.50%) 
Gait disturbance * 1  0/41 (0.00%)  1/40 (2.50%) 
Generalised oedema * 1  0/41 (0.00%)  1/40 (2.50%) 
Oedema peripheral * 1  0/41 (0.00%)  1/40 (2.50%) 
Infections and infestations     
Aspergillosis * 1  0/41 (0.00%)  1/40 (2.50%) 
Brain abscess * 1  1/41 (2.44%)  0/40 (0.00%) 
Cellulitis * 1  1/41 (2.44%)  1/40 (2.50%) 
Clostridium colitis * 1  1/41 (2.44%)  0/40 (0.00%) 
Herpes zoster * 1  1/41 (2.44%)  1/40 (2.50%) 
Sepsis * 1  1/41 (2.44%)  0/40 (0.00%) 
Investigations     
Blood glucose increased * 1  0/41 (0.00%)  1/40 (2.50%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness * 1  1/41 (2.44%)  0/40 (0.00%) 
Nervous system disorders     
Amnesia * 1  1/41 (2.44%)  0/40 (0.00%) 
Aphasia * 1  2/41 (4.88%)  3/40 (7.50%) 
Ataxia * 1  1/41 (2.44%)  1/40 (2.50%) 
Brain oedema * 1  2/41 (4.88%)  0/40 (0.00%) 
Cerebral haemorrhage * 1  1/41 (2.44%)  0/40 (0.00%) 
Convulsion * 1  5/41 (12.20%)  8/40 (20.00%) 
Grand mal convulsion * 1  1/41 (2.44%)  0/40 (0.00%) 
Headache * 1  5/41 (12.20%)  2/40 (5.00%) 
Hemiparesis * 1  1/41 (2.44%)  1/40 (2.50%) 
Hemiplegia * 1  1/41 (2.44%)  0/40 (0.00%) 
Motor dysfunction * 1  1/41 (2.44%)  0/40 (0.00%) 
Neurologic neglect syndrome * 1  0/41 (0.00%)  1/40 (2.50%) 
Neuropathy * 1  1/41 (2.44%)  0/40 (0.00%) 
Peripheral sensory neuropathy * 1  1/41 (2.44%)  0/40 (0.00%) 
Postictal paralysis * 1  1/41 (2.44%)  0/40 (0.00%) 
Somnolence * 1  1/41 (2.44%)  0/40 (0.00%) 
Psychiatric disorders     
Affective disorder * 1  1/41 (2.44%)  0/40 (0.00%) 
Confusional state * 1  1/41 (2.44%)  0/40 (0.00%) 
Mental status changes * 1  2/41 (4.88%)  1/40 (2.50%) 
Renal and urinary disorders     
Renal failure * 1  1/41 (2.44%)  0/40 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia aspiration * 1  1/41 (2.44%)  1/40 (2.50%) 
Pulmonary embolism * 1  0/41 (0.00%)  3/40 (7.50%) 
Pulmonary oedema * 1  1/41 (2.44%)  0/40 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  2/41 (4.88%)  2/40 (5.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 7.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cilengitide 500 Milligram (mg) Cilengitide 2000 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   41/41 (100.00%)   39/40 (97.50%) 
Blood and lymphatic system disorders     
Haemoglobinaemia * 1  1/41 (2.44%)  0/40 (0.00%) 
Leukopenia * 1  0/41 (0.00%)  1/40 (2.50%) 
Lymphopenia * 1  2/41 (4.88%)  2/40 (5.00%) 
Neutropenia * 1  1/41 (2.44%)  1/40 (2.50%) 
Thrombocytopenia * 1  2/41 (4.88%)  1/40 (2.50%) 
Ear and labyrinth disorders     
Deafness * 1  1/41 (2.44%)  0/40 (0.00%) 
Ear pain * 1  2/41 (4.88%)  2/40 (5.00%) 
Middle ear effusion * 1  1/41 (2.44%)  0/40 (0.00%) 
Otorrhoea * 1  1/41 (2.44%)  0/40 (0.00%) 
Tinnitus * 1  1/41 (2.44%)  1/40 (2.50%) 
Tympanic membrane perforation * 1  0/41 (0.00%)  1/40 (2.50%) 
Vertigo * 1  1/41 (2.44%)  0/40 (0.00%) 
Endocrine disorders     
Cushingoid * 1  5/41 (12.20%)  3/40 (7.50%) 
Hirsutism * 1  1/41 (2.44%)  0/40 (0.00%) 
Eye disorders     
Cataract * 1  0/41 (0.00%)  1/40 (2.50%) 
Conjunctival haemorrhage * 1  0/41 (0.00%)  1/40 (2.50%) 
Conjunctivitis * 1  1/41 (2.44%)  1/40 (2.50%) 
Diplopia * 1  1/41 (2.44%)  2/40 (5.00%) 
Dry eye * 1  1/41 (2.44%)  0/40 (0.00%) 
Eye irritation * 1  1/41 (2.44%)  0/40 (0.00%) 
Eye pain * 1  0/41 (0.00%)  1/40 (2.50%) 
Eyelid oedema * 1  0/41 (0.00%)  1/40 (2.50%) 
Gaze palsy * 1  0/41 (0.00%)  1/40 (2.50%) 
Glaucoma * 1  0/41 (0.00%)  1/40 (2.50%) 
Lacrimation increased * 1  1/41 (2.44%)  0/40 (0.00%) 
Ophthalmoplegia * 1  1/41 (2.44%)  0/40 (0.00%) 
Papilloedema * 1  1/41 (2.44%)  1/40 (2.50%) 
Photophobia * 1  1/41 (2.44%)  0/40 (0.00%) 
Scleral haemorrhage * 1  1/41 (2.44%)  0/40 (0.00%) 
Vision blurred * 1  5/41 (12.20%)  3/40 (7.50%) 
Visual acuity reduced * 1  5/41 (12.20%)  1/40 (2.50%) 
Vitreous floaters * 1  1/41 (2.44%)  0/40 (0.00%) 
Gastrointestinal disorders     
Abdominal distension * 1  3/41 (7.32%)  1/40 (2.50%) 
Abdominal pain * 1  2/41 (4.88%)  3/40 (7.50%) 
Abdominal pain upper * 1  1/41 (2.44%)  1/40 (2.50%) 
Chapped lips * 1  0/41 (0.00%)  1/40 (2.50%) 
Constipation * 1  3/41 (7.32%)  4/40 (10.00%) 
Diarrhoea * 1  7/41 (17.07%)  5/40 (12.50%) 
Dry mouth * 1  0/41 (0.00%)  1/40 (2.50%) 
Dyspepsia * 1  3/41 (7.32%)  3/40 (7.50%) 
Dysphagia * 1  0/41 (0.00%)  1/40 (2.50%) 
Faecal incontinence * 1  1/41 (2.44%)  0/40 (0.00%) 
Flatulence * 1  3/41 (7.32%)  0/40 (0.00%) 
Gastrooesophageal reflux disease * 1  1/41 (2.44%)  1/40 (2.50%) 
Gingival hypertrophy * 1  1/41 (2.44%)  0/40 (0.00%) 
Gingivitis * 1  0/41 (0.00%)  1/40 (2.50%) 
Haematochezia * 1  1/41 (2.44%)  0/40 (0.00%) 
Haemorrhoids * 1  1/41 (2.44%)  1/40 (2.50%) 
Lip disorder * 1  0/41 (0.00%)  1/40 (2.50%) 
Lip dry * 1  0/41 (0.00%)  1/40 (2.50%) 
Loose stools * 1  1/41 (2.44%)  1/40 (2.50%) 
Nausea * 1  10/41 (24.39%)  6/40 (15.00%) 
Stomach discomfort * 1  0/41 (0.00%)  1/40 (2.50%) 
Toothache * 1  1/41 (2.44%)  0/40 (0.00%) 
Vomiting * 1  3/41 (7.32%)  2/40 (5.00%) 
General disorders     
Abasia * 1  1/41 (2.44%)  0/40 (0.00%) 
Adverse drug reaction * 1  1/41 (2.44%)  0/40 (0.00%) 
Asthenia * 1  1/41 (2.44%)  6/40 (15.00%) 
Catheter related complication * 1  0/41 (0.00%)  1/40 (2.50%) 
Catheter site haemorrhage * 1  2/41 (4.88%)  0/40 (0.00%) 
Catheter site oedema * 1  1/41 (2.44%)  0/40 (0.00%) 
Catheter site pain * 1  1/41 (2.44%)  2/40 (5.00%) 
Chest discomfort * 1  1/41 (2.44%)  0/40 (0.00%) 
Chest pain * 1  0/41 (0.00%)  1/40 (2.50%) 
Chills * 1  1/41 (2.44%)  1/40 (2.50%) 
Cyst * 1  0/41 (0.00%)  2/40 (5.00%) 
Difficulty in walking * 1  1/41 (2.44%)  1/40 (2.50%) 
Facial pain * 1  0/41 (0.00%)  1/40 (2.50%) 
Fatigue * 1  11/41 (26.83%)  18/40 (45.00%) 
Gait disturbance * 1  4/41 (9.76%)  6/40 (15.00%) 
Influenza like illness * 1  1/41 (2.44%)  0/40 (0.00%) 
Infusion site pain * 1  0/41 (0.00%)  1/40 (2.50%) 
Infusion site reaction * 1  1/41 (2.44%)  0/40 (0.00%) 
Malaise * 1  0/41 (0.00%)  1/40 (2.50%) 
Mucosal inflammation * 1  1/41 (2.44%)  0/40 (0.00%) 
Oedema * 1  1/41 (2.44%)  0/40 (0.00%) 
Oedema peripheral * 1  12/41 (29.27%)  10/40 (25.00%) 
Pitting oedema * 1  1/41 (2.44%)  0/40 (0.00%) 
Pyrexia * 1  2/41 (4.88%)  3/40 (7.50%) 
Temperature intolerance * 1  1/41 (2.44%)  1/40 (2.50%) 
Venipuncture site bruise * 1  1/41 (2.44%)  0/40 (0.00%) 
Hepatobiliary disorders     
Hyperbilirubinaemia * 1  0/41 (0.00%)  1/40 (2.50%) 
Immune system disorders     
Hypersensitivity * 1  1/41 (2.44%)  1/40 (2.50%) 
Seasonal allergy * 1  2/41 (4.88%)  0/40 (0.00%) 
Infections and infestations     
Bacteriuria * 1  1/41 (2.44%)  0/40 (0.00%) 
Body tinea * 1  1/41 (2.44%)  0/40 (0.00%) 
Candidiasis * 1  0/41 (0.00%)  2/40 (5.00%) 
Cellulitis * 1  1/41 (2.44%)  2/40 (5.00%) 
Conjunctivitis infective * 1  1/41 (2.44%)  0/40 (0.00%) 
Cystitis * 1  1/41 (2.44%)  0/40 (0.00%) 
Dental caries * 1  1/41 (2.44%)  0/40 (0.00%) 
Eczema infected * 1  0/41 (0.00%)  1/40 (2.50%) 
Escherichia urinary tract infection * 1  1/41 (2.44%)  0/40 (0.00%) 
Eye infection * 1  1/41 (2.44%)  1/40 (2.50%) 
Folliculitis * 1  0/41 (0.00%)  1/40 (2.50%) 
Gastroenteritis * 1  2/41 (4.88%)  0/40 (0.00%) 
Herpes simplex * 1  1/41 (2.44%)  0/40 (0.00%) 
Herpes zoster * 1  1/41 (2.44%)  0/40 (0.00%) 
Hordeolum * 1  1/41 (2.44%)  0/40 (0.00%) 
Influenza * 1  0/41 (0.00%)  1/40 (2.50%) 
Localised infection * 1  0/41 (0.00%)  1/40 (2.50%) 
Nasopharyngitis * 1  2/41 (4.88%)  1/40 (2.50%) 
Oral infection * 1  1/41 (2.44%)  0/40 (0.00%) 
Otitis externa * 1  0/41 (0.00%)  1/40 (2.50%) 
Otitis media * 1  0/41 (0.00%)  1/40 (2.50%) 
Respiratory tract infection * 1  1/41 (2.44%)  0/40 (0.00%) 
Rhinitis * 1  1/41 (2.44%)  0/40 (0.00%) 
Sialoadenitis * 1  1/41 (2.44%)  0/40 (0.00%) 
Sinusitis * 1  3/41 (7.32%)  2/40 (5.00%) 
Tooth abscess * 1  1/41 (2.44%)  0/40 (0.00%) 
Upper respiratory tract infection * 1  5/41 (12.20%)  2/40 (5.00%) 
Urinary tract infection * 1  4/41 (9.76%)  3/40 (7.50%) 
Viral upper respiratory tract infection * 1  0/41 (0.00%)  1/40 (2.50%) 
Injury, poisoning and procedural complications     
Arthropod bite * 1  1/41 (2.44%)  0/40 (0.00%) 
Back injury * 1  0/41 (0.00%)  1/40 (2.50%) 
Blood blister * 1  0/41 (0.00%)  1/40 (2.50%) 
Contusion * 1  3/41 (7.32%)  3/40 (7.50%) 
Excoriation * 1  2/41 (4.88%)  0/40 (0.00%) 
Fall * 1  6/41 (14.63%)  3/40 (7.50%) 
Hand fracture * 1  1/41 (2.44%)  0/40 (0.00%) 
Joint sprain * 1  0/41 (0.00%)  1/40 (2.50%) 
Post procedural pain * 1  1/41 (2.44%)  0/40 (0.00%) 
Rib fracture * 1  0/41 (0.00%)  1/40 (2.50%) 
Skin laceration * 1  1/41 (2.44%)  3/40 (7.50%) 
Tibia fracture * 1  0/41 (0.00%)  1/40 (2.50%) 
Tooth injury * 1  1/41 (2.44%)  0/40 (0.00%) 
Investigations     
Activated partial thromboplastin time prolonged * 1  0/41 (0.00%)  1/40 (2.50%) 
Activated partial thromboplastin time shortened * 1  0/41 (0.00%)  1/40 (2.50%) 
Alanine aminotransferase increased * 1  2/41 (4.88%)  2/40 (5.00%) 
Anticonvulsant drug level increased * 1  2/41 (4.88%)  1/40 (2.50%) 
Aspartate aminotransferase increased * 1  0/41 (0.00%)  2/40 (5.00%) 
Bacteria urine * 1  3/41 (7.32%)  0/40 (0.00%) 
Blood alkaline phosphatase increased * 1  1/41 (2.44%)  1/40 (2.50%) 
Blood cholesterol increased * 1  2/41 (4.88%)  1/40 (2.50%) 
Blood glucose increased * 1  1/41 (2.44%)  0/40 (0.00%) 
Blood iron decreased * 1  1/41 (2.44%)  0/40 (0.00%) 
Blood potassium decreased * 1  0/41 (0.00%)  1/40 (2.50%) 
Blood urea increased * 1  2/41 (4.88%)  0/40 (0.00%) 
Cardiac murmur * 1  0/41 (0.00%)  1/40 (2.50%) 
Electrocardiogram ST segment elevation * 1  1/41 (2.44%)  0/40 (0.00%) 
Electrocardiogram abnormal * 1  1/41 (2.44%)  0/40 (0.00%) 
Haemoglobin decreased * 1  1/41 (2.44%)  0/40 (0.00%) 
Neutrophil count decreased * 1  0/41 (0.00%)  1/40 (2.50%) 
Neutrophil count increased * 1  2/41 (4.88%)  0/40 (0.00%) 
Nuclear magnetic resonance imaging abnormal * 1  1/41 (2.44%)  0/40 (0.00%) 
Platelet count decreased * 1  1/41 (2.44%)  0/40 (0.00%) 
Prothrombin time * 1  0/41 (0.00%)  1/40 (2.50%) 
Red blood cell count decreased * 1  1/41 (2.44%)  0/40 (0.00%) 
Tandem gait test abnormal * 1  1/41 (2.44%)  1/40 (2.50%) 
Weight decreased * 1  0/41 (0.00%)  1/40 (2.50%) 
Weight increased * 1  1/41 (2.44%)  2/40 (5.00%) 
White blood cell count decreased * 1  0/41 (0.00%)  1/40 (2.50%) 
White blood cells urine positive * 1  2/41 (4.88%)  0/40 (0.00%) 
Metabolism and nutrition disorders     
Anorexia * 1  1/41 (2.44%)  0/40 (0.00%) 
Dehydration * 1  2/41 (4.88%)  0/40 (0.00%) 
Diabetes mellitus * 1  0/41 (0.00%)  1/40 (2.50%) 
Hypercholesterolaemia * 1  0/41 (0.00%)  2/40 (5.00%) 
Hyperglycaemia * 1  1/41 (2.44%)  5/40 (12.50%) 
Hyperkalaemia * 1  1/41 (2.44%)  0/40 (0.00%) 
Hypernatraemia * 1  1/41 (2.44%)  0/40 (0.00%) 
Hyperphosphataemia * 1  1/41 (2.44%)  0/40 (0.00%) 
Hypoalbuminaemia * 1  1/41 (2.44%)  0/40 (0.00%) 
Hypocalcaemia * 1  1/41 (2.44%)  0/40 (0.00%) 
Hypokalaemia * 1  4/41 (9.76%)  0/40 (0.00%) 
Hypomagnesaemia * 1  1/41 (2.44%)  0/40 (0.00%) 
Hyponatraemia * 1  1/41 (2.44%)  1/40 (2.50%) 
Hypophosphataemia * 1  1/41 (2.44%)  0/40 (0.00%) 
Increased appetite * 1  0/41 (0.00%)  1/40 (2.50%) 
Markedly reduced dietary intake * 1  1/41 (2.44%)  0/40 (0.00%) 
Tetany * 1  0/41 (0.00%)  1/40 (2.50%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  9/41 (21.95%)  2/40 (5.00%) 
Arthritis * 1  1/41 (2.44%)  0/40 (0.00%) 
Back pain * 1  4/41 (9.76%)  8/40 (20.00%) 
Bone pain * 1  1/41 (2.44%)  0/40 (0.00%) 
Joint effusion * 1  1/41 (2.44%)  0/40 (0.00%) 
Joint stiffness * 1  1/41 (2.44%)  0/40 (0.00%) 
Joint swelling * 1  1/41 (2.44%)  0/40 (0.00%) 
Muscle cramp * 1  2/41 (4.88%)  3/40 (7.50%) 
Muscle spasms * 1  0/41 (0.00%)  1/40 (2.50%) 
Muscular weakness * 1  5/41 (12.20%)  4/40 (10.00%) 
Musculoskeletal chest pain * 1  1/41 (2.44%)  0/40 (0.00%) 
Musculoskeletal discomfort * 1  1/41 (2.44%)  0/40 (0.00%) 
Myalgia * 1  2/41 (4.88%)  0/40 (0.00%) 
Myopathy steroid * 1  1/41 (2.44%)  1/40 (2.50%) 
Neck pain * 1  0/41 (0.00%)  1/40 (2.50%) 
Pain in extremity * 1  3/41 (7.32%)  2/40 (5.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin papilloma * 1  1/41 (2.44%)  0/40 (0.00%) 
Nervous system disorders     
Amnesia * 1  8/41 (19.51%)  5/40 (12.50%) 
Aphasia * 1  5/41 (12.20%)  9/40 (22.50%) 
Ataxia * 1  1/41 (2.44%)  3/40 (7.50%) 
Aura * 1  2/41 (4.88%)  0/40 (0.00%) 
Balance disorder * 1  7/41 (17.07%)  2/40 (5.00%) 
Brain oedema * 1  0/41 (0.00%)  1/40 (2.50%) 
Cognitive disorder * 1  2/41 (4.88%)  1/40 (2.50%) 
Convulsion * 1  7/41 (17.07%)  4/40 (10.00%) 
Coordination abnormal * 1  2/41 (4.88%)  1/40 (2.50%) 
Cranial nerve disorder * 1  1/41 (2.44%)  2/40 (5.00%) 
Cranial neuropathy * 1  3/41 (7.32%)  1/40 (2.50%) 
Disturbance in attention * 1  3/41 (7.32%)  0/40 (0.00%) 
Dizziness * 1  7/41 (17.07%)  7/40 (17.50%) 
Dysarthria * 1  3/41 (7.32%)  1/40 (2.50%) 
Dysgeusia * 1  1/41 (2.44%)  0/40 (0.00%) 
Dysgraphia * 1  0/41 (0.00%)  1/40 (2.50%) 
Dyskinesia * 1  0/41 (0.00%)  1/40 (2.50%) 
Dysphasia * 1  0/41 (0.00%)  1/40 (2.50%) 
Facial palsy * 1  1/41 (2.44%)  3/40 (7.50%) 
Facial paresis * 1  5/41 (12.20%)  0/40 (0.00%) 
Grand mal convulsion * 1  1/41 (2.44%)  1/40 (2.50%) 
Headache * 1  14/41 (34.15%)  14/40 (35.00%) 
Hemianopia homonymous * 1  1/41 (2.44%)  0/40 (0.00%) 
Hemiparesis * 1  3/41 (7.32%)  4/40 (10.00%) 
Hemiplegia * 1  1/41 (2.44%)  0/40 (0.00%) 
Hyperaesthesia * 1  0/41 (0.00%)  1/40 (2.50%) 
Hyperreflexia * 1  0/41 (0.00%)  1/40 (2.50%) 
Hypoaesthesia * 1  2/41 (4.88%)  2/40 (5.00%) 
Lethargy * 1  2/41 (4.88%)  1/40 (2.50%) 
Memory impairment * 1  4/41 (9.76%)  5/40 (12.50%) 
Motor dysfunction * 1  4/41 (9.76%)  2/40 (5.00%) 
Neurologic neglect syndrome * 1  2/41 (4.88%)  1/40 (2.50%) 
Neuropathic pain * 1  0/41 (0.00%)  1/40 (2.50%) 
Neuropathy * 1  2/41 (4.88%)  0/40 (0.00%) 
Nystagmus * 1  1/41 (2.44%)  2/40 (5.00%) 
Paraesthesia * 1  2/41 (4.88%)  2/40 (5.00%) 
Partial seizures * 1  1/41 (2.44%)  1/40 (2.50%) 
Peripheral sensory neuropathy * 1  0/41 (0.00%)  3/40 (7.50%) 
Peroneal nerve palsy * 1  0/41 (0.00%)  1/40 (2.50%) 
Pyramidal tract syndrome * 1  1/41 (2.44%)  0/40 (0.00%) 
Reflex sympathetic dystrophy * 1  1/41 (2.44%)  0/40 (0.00%) 
Sensory disturbance * 1  1/41 (2.44%)  1/40 (2.50%) 
Simple partial seizures * 1  1/41 (2.44%)  2/40 (5.00%) 
Sinus headache * 1  1/41 (2.44%)  0/40 (0.00%) 
Somnolence * 1  1/41 (2.44%)  2/40 (5.00%) 
Speech disorder * 1  4/41 (9.76%)  3/40 (7.50%) 
Tremor * 1  4/41 (9.76%)  4/40 (10.00%) 
Upper motor neurone lesion * 1  2/41 (4.88%)  0/40 (0.00%) 
Visual field defect * 1  1/41 (2.44%)  0/40 (0.00%) 
Psychiatric disorders     
Affect lability * 1  1/41 (2.44%)  1/40 (2.50%) 
Aggression * 1  0/41 (0.00%)  1/40 (2.50%) 
Agitation * 1  2/41 (4.88%)  1/40 (2.50%) 
Anxiety * 1  2/41 (4.88%)  3/40 (7.50%) 
Cognitive deterioration * 1  0/41 (0.00%)  1/40 (2.50%) 
Confusional state * 1  8/41 (19.51%)  7/40 (17.50%) 
Depression * 1  3/41 (7.32%)  6/40 (15.00%) 
Disorientation * 1  0/41 (0.00%)  1/40 (2.50%) 
Insomnia * 1  4/41 (9.76%)  6/40 (15.00%) 
Irritability * 1  2/41 (4.88%)  0/40 (0.00%) 
Mental status changes * 1  1/41 (2.44%)  0/40 (0.00%) 
Mood altered * 1  2/41 (4.88%)  1/40 (2.50%) 
Nervousness * 1  1/41 (2.44%)  0/40 (0.00%) 
Personality change * 1  1/41 (2.44%)  2/40 (5.00%) 
Psychomotor retardation * 1  1/41 (2.44%)  0/40 (0.00%) 
Psychotic disorder * 1  0/41 (0.00%)  1/40 (2.50%) 
Renal and urinary disorders     
Haematuria * 1  1/41 (2.44%)  1/40 (2.50%) 
Leukocyturia * 1  1/41 (2.44%)  0/40 (0.00%) 
Micturition urgency * 1  2/41 (4.88%)  1/40 (2.50%) 
Nephrolithiasis * 1  1/41 (2.44%)  1/40 (2.50%) 
Pollakiuria * 1  2/41 (4.88%)  0/40 (0.00%) 
Proteinuria * 1  4/41 (9.76%)  0/40 (0.00%) 
Renal salt-wasting syndrome * 1  0/41 (0.00%)  1/40 (2.50%) 
Urinary incontinence * 1  4/41 (9.76%)  4/40 (10.00%) 
Reproductive system and breast disorders     
Breast pain * 1  1/41 (2.44%)  0/40 (0.00%) 
Menstrual disorder * 1  1/41 (2.44%)  0/40 (0.00%) 
Nipple pain * 1  0/41 (0.00%)  1/40 (2.50%) 
Polymenorrhoea * 1  1/41 (2.44%)  0/40 (0.00%) 
Prostatitis * 1  1/41 (2.44%)  0/40 (0.00%) 
Sexual dysfunction * 1  1/41 (2.44%)  2/40 (5.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  2/41 (4.88%)  4/40 (10.00%) 
Dyspnoea * 1  1/41 (2.44%)  5/40 (12.50%) 
Hoarseness * 1  0/41 (0.00%)  1/40 (2.50%) 
Hypoxia * 1  0/41 (0.00%)  1/40 (2.50%) 
Nasal congestion * 1  2/41 (4.88%)  0/40 (0.00%) 
Nasal dryness * 1  0/41 (0.00%)  1/40 (2.50%) 
Pharyngolaryngeal pain * 1  2/41 (4.88%)  0/40 (0.00%) 
Respiratory tract congestion * 1  1/41 (2.44%)  0/40 (0.00%) 
Sinus congestion * 1  1/41 (2.44%)  0/40 (0.00%) 
Snoring * 1  1/41 (2.44%)  0/40 (0.00%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  1/41 (2.44%)  0/40 (0.00%) 
Dermal cyst * 1  0/41 (0.00%)  1/40 (2.50%) 
Dermatitis contact * 1  1/41 (2.44%)  1/40 (2.50%) 
Dry skin * 1  2/41 (4.88%)  1/40 (2.50%) 
Ecchymosis * 1  2/41 (4.88%)  1/40 (2.50%) 
Erythema * 1  1/41 (2.44%)  0/40 (0.00%) 
Face oedema * 1  0/41 (0.00%)  1/40 (2.50%) 
Hyperhidrosis * 1  0/41 (0.00%)  1/40 (2.50%) 
Photosensitivity reaction * 1  0/41 (0.00%)  1/40 (2.50%) 
Pruritus * 1  2/41 (4.88%)  1/40 (2.50%) 
Rash * 1  6/41 (14.63%)  7/40 (17.50%) 
Rash erythematous * 1  1/41 (2.44%)  0/40 (0.00%) 
Rash generalised * 1  1/41 (2.44%)  0/40 (0.00%) 
Rash pruritic * 1  1/41 (2.44%)  0/40 (0.00%) 
Skin discolouration * 1  0/41 (0.00%)  1/40 (2.50%) 
Skin fragility * 1  0/41 (0.00%)  1/40 (2.50%) 
Vascular disorders     
Deep vein thrombosis * 1  2/41 (4.88%)  0/40 (0.00%) 
Hypertension * 1  1/41 (2.44%)  0/40 (0.00%) 
Hypotension * 1  0/41 (0.00%)  2/40 (5.00%) 
Petechiae * 1  2/41 (4.88%)  1/40 (2.50%) 
Phlebitis * 1  0/41 (0.00%)  1/40 (2.50%) 
Phlebitis superficial * 1  0/41 (0.00%)  1/40 (2.50%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 7.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Layout table for additonal information
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00093964    
Obsolete Identifiers: NCT00103064, NCT00119288
Other Study ID Numbers: EMD 121974-009
First Submitted: October 7, 2004
First Posted: October 11, 2004
Results First Submitted: October 2, 2017
Results First Posted: April 16, 2019
Last Update Posted: April 16, 2019