Trial Outcomes & Findings for Phase 3 Study of Immunotherapy to Treat Advanced Prostate Cancer (NCT NCT01057810)
NCT ID: NCT01057810
Last Updated: 2016-08-18
Results Overview
OS was defined as the time from the date of randomization until the date of death. For participants without documentation of death, OS was censored at the last date the participant was known to be alive.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
837 participants
Primary outcome timeframe
Randomization until death from any cause, up to April 2015, approximately 57 months
Results posted on
2016-08-18
Participant Flow
837 participants enrolled; 602 randomized; 598 treated. Of the 235 not randomized, 189 no longer met criteria, 28 withdrew consent, 2 suffered Adverse Events, 2 were non-compliant, 1 was lost to follow-up, and 13 were removed for other/unspecified reasons. Post-randomization, 4 no longer met criteria and were not treated (3 placebo, 1 ipilimumab)
Participant milestones
| Measure |
Placebo
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Overall Study
STARTED
|
199
|
399
|
|
Overall Study
COMPLETED
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
198
|
398
|
Reasons for withdrawal
| Measure |
Placebo
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Overall Study
Disease progression
|
156
|
197
|
|
Overall Study
Study drug toxicity
|
5
|
114
|
|
Overall Study
Adverse event unrelated to study drug
|
13
|
29
|
|
Overall Study
Withdrawal by Subject
|
10
|
25
|
|
Overall Study
Death
|
2
|
12
|
|
Overall Study
Maximum clinical benefit
|
5
|
5
|
|
Overall Study
Poor/non-compliance
|
0
|
1
|
|
Overall Study
No longer met study criteria
|
0
|
1
|
|
Overall Study
Other
|
7
|
14
|
Baseline Characteristics
Phase 3 Study of Immunotherapy to Treat Advanced Prostate Cancer
Baseline characteristics by cohort
| Measure |
Placebo
n=202 Participants
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
n=400 Participants
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Total
n=602 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
68.6 years
n=5 Participants
|
69.3 years
n=7 Participants
|
69.0 years
n=5 Participants
|
|
Age, Customized
< 65 years
|
65 participants
n=5 Participants
|
104 participants
n=7 Participants
|
169 participants
n=5 Participants
|
|
Age, Customized
>= 65 years
|
137 participants
n=5 Participants
|
296 participants
n=7 Participants
|
433 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
202 Participants
n=5 Participants
|
400 Participants
n=7 Participants
|
602 Participants
n=5 Participants
|
|
Region of Enrollment
North America
|
79 participants
n=5 Participants
|
154 participants
n=7 Participants
|
233 participants
n=5 Participants
|
|
Region of Enrollment
South America
|
25 participants
n=5 Participants
|
52 participants
n=7 Participants
|
77 participants
n=5 Participants
|
|
Region of Enrollment
Europe
|
74 participants
n=5 Participants
|
161 participants
n=7 Participants
|
235 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
24 participants
n=5 Participants
|
33 participants
n=7 Participants
|
57 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization until death from any cause, up to April 2015, approximately 57 monthsPopulation: All randomized participants
OS was defined as the time from the date of randomization until the date of death. For participants without documentation of death, OS was censored at the last date the participant was known to be alive.
Outcome measures
| Measure |
Placebo
n=202 Participants
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
n=400 Participants
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Overall Survival (OS) Time
|
29.73 months
Interval 26.12 to 34.17
|
28.65 months
Interval 24.48 to 32.46
|
SECONDARY outcome
Timeframe: Randomization until disease progression, up to April 2015, approximately 57 monthsPopulation: All randomized participants
Progression-free survival, as determined by the investigator, was defined as the time from randomization to the earliest date of confirmed Prostate-Specific Antigen (PSA) progression, confirmed radiological progression, clinical deterioration, or death.
Outcome measures
| Measure |
Placebo
n=202 Participants
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
n=400 Participants
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Progression-Free Survival (PFS) Time
|
3.81 months
Interval 2.76 to 4.11
|
5.59 months
Interval 5.32 to 6.28
|
SECONDARY outcome
Timeframe: Randomization until subsequent non-hormonal cytotoxic therapy, up to April 2015, approximately 57 monthsPopulation: All randomized participants who received subsequent non-hormonal cytotoxic therapy
For participants who discontinued treatment or experienced disease progression while on study therapy and then received subsequent non-hormonal cytotoxic therapy, time to subsequent non-hormonal cytotoxic therapy was defined as the time from randomization to the time of initiation of subsequent non-hormonal cytotoxic therapy. Participants who did not receive subsequent non-hormonal cytotoxic therapy were censored on the last known alive date (for participants who have not died) or the date of last follow-up contact at which the participants was known alive (for participants who died).
Outcome measures
| Measure |
Placebo
n=128 Participants
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
n=199 Participants
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Time to Subsequent Non-hormonal Cytotoxic Therapy
|
10.91 months
Interval 8.44 to 14.59
|
18.04 months
Interval 15.18 to 24.8
|
SECONDARY outcome
Timeframe: Randomization until pain progression, up to April 2015, approximately 57 monthsPopulation: All randomized participants
Time to pain progression was defined as the time from randomization to the time of the earliest date of any of the following 4 events: 1) an increase in average daily worst pain intensity of \>= 2 points from baseline according to the Brief Pain Inventory - Short Form (BPI-SF), maintained over 2 consecutive time periods. 2) initiation of opioid analgesic (excluding codeine or dextropropoxyphene). 3) initiation of palliative radiotherapy for prostate cancer. 4) increase in mean Analgesic Score (AS) of \>= 25% from baseline (for participants with baseline AS \> 10) or increase in mean AS \>= 10 points from baseline (for participants with baseline AS \<= 10). Participants who did not experience any of these events were censored on the earliest date among the latest BPI-SF completion date with non-missing worst pain assessment and last evaluable disease assessment date as defined in the PFS censoring mechanism.
Outcome measures
| Measure |
Placebo
n=202 Participants
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
n=400 Participants
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Time to Pain Progression
|
16.62 months
Interval 11.53 to
Upper bounds were not estimable due to censoring
|
21.68 months
Interval 19.22 to
Upper bounds were not estimable due to censoring
|
SECONDARY outcome
Timeframe: Day 1 of study therapy to last dose plus 70 daysPopulation: All treated participants
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. irAE=AEs consistent with an immune mediated mechanism. imAR=AEs of special interest that were adjudicated as imAR by investigator. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Events were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Outcome measures
| Measure |
Placebo
n=199 Participants
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
n=399 Participants
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
AE (grade 3-4)
|
59 participants
|
223 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
Drug-related AE (any grade)
|
98 participants
|
325 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
Drug-related AE (grade 3-4)
|
11 participants
|
158 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
SAE (any grade)
|
53 participants
|
213 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
SAE (grade 3-4)
|
39 participants
|
153 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
AE leading to DC (any grade)
|
20 participants
|
139 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
AE leading to DC (grade 3-4)
|
14 participants
|
103 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
irAE (any grade)
|
57 participants
|
309 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
irAE (grade 3-4)
|
3 participants
|
125 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
imAR (grade >= 2)
|
14 participants
|
273 participants
|
|
Number of Participants Who Died or Had Adverse Events (AEs), Serious Adverse Events (SAEs), Immune-related AEs (irAEs), or Immune-mediated Adverse Reactions (imARs)
Deaths
|
130 participants
|
259 participants
|
SECONDARY outcome
Timeframe: Randomization up to April 2015, approximately 57 monthsPopulation: All treated participants with on-study laboratory results
NCI CTC, Version 3 used to assess parameters. LLN=lower limit of normal. ULN=upper limit of normal. CTC criteria: White blood cells (WBC): Gr 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L. Absolute neutrophil count (ANC): Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count: Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Hemoglobin: Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Absolute Lymphocyte Count (ALC): Gr 3: 0.2 - \<0.5\*10\^9/L, Gr 4: \<0.2\*10\^9/L. Lipase: Gr 3:\> 2.0 - 5.0 \* ULN; Gr 4: \> 5.0 X ULN. Amylase: Gr 3: \> 2.0 - 5.0 \* ULN; Gr 4: \> 5.0 \* ULN. Alanine Aminotransferase (ALT) Gr 3: \> 5.0 - 20.0 \* ULN; Gr 4: \> 20.0 \* ULN. Aspartate Aminotransferase (AST): Gr 3: \> 5.0 - 20.0 \* ULN; Gr 4: \> 20.0 \* ULN. Bilirubin: Gr 3: \> 3.0 - 10.0 \* ULN; Gr 4: \> 10.0 \* ULN. Alkaline Phosphatase: Gr 3: \> 5.0 - 20.0 \* ULN; Gr 4: \> 20.0 \* ULN. Creatinine: Gr 3: \> 3.0-6.0 \* ULN, Gr 4: \>6.0 \* ULN.
Outcome measures
| Measure |
Placebo
n=198 Participants
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
Ipilimumab
n=386 Participants
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
WBC (n=195;383)
|
0 participants
|
3 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
ANC (n=195;383)
|
0 participants
|
2 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
Platelet count (n=194;381)
|
0 participants
|
2 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
Hemoglobin (n=195;383)
|
2 participants
|
5 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
ALC (n=195;383)
|
4 participants
|
12 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
Lipase (n=196;382)
|
4 participants
|
27 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
Amylase (n=198;385)
|
2 participants
|
9 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
ALT (n=198;386)
|
1 participants
|
16 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
AST (n=196;383)
|
1 participants
|
18 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
Total Bilirubin (n=198;386)
|
0 participants
|
4 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
Alkaline phosphatase (n=196;383)
|
11 participants
|
18 participants
|
|
Number of Treated Participants With Grade 3 or 4 Clinical Laboratory Abnormalities
Creatinine (n=9;23)
|
0 participants
|
0 participants
|
Adverse Events
PLACEBO
Serious events: 53 serious events
Other events: 166 other events
Deaths: 0 deaths
10 MG/KG IPILIMUMAB
Serious events: 213 serious events
Other events: 361 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PLACEBO
n=199 participants at risk
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
10 MG/KG IPILIMUMAB
n=399 participants at risk
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Anuria
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Arterial thrombosis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Chest pain
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Cluster headache
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Coeliac disease
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis exfoliative
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Psychiatric disorders
Drug dependence
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Dysuria
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Embolism
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Endocrine disorder
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Myasthenia gravis crisis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
2.5%
10/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Pain
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Renal cyst haemorrhage
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Secondary adrenocortical insufficiency
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Sepsis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Sinusitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Urinary retention
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Viral infection
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Abscess limb
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Atrial tachycardia
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Bladder obstruction
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Cellulitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Cerebrovascular accident
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal adenocarcinoma
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.8%
7/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Enterocolitis bacterial
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
General physical health deterioration
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Infection
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Mucosal inflammation
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.5%
6/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Pyelonephritis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Secondary hypothyroidism
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Urogenital disorder
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Eye disorders
Eye disorder
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Mononeuropathy
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Thrombosis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Transaminases increased
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Urinary tract infection fungal
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Abscess
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Agranulocytosis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Cauda equina syndrome
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Death
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Deep vein thrombosis
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Psychiatric disorders
Depressed mood
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
11.8%
47/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Gastrointestinal necrosis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Hernial eventration
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Nephritis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Obstructive uropathy
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Pneumonia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
3.3%
13/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Ureteric obstruction
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Urinary tract infection
|
3.0%
6/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Vomiting
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
1.5%
6/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Adrenocortical insufficiency acute
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Colitis
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
7.3%
29/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Cytomegalovirus colitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Psychiatric disorders
Delirium
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Febrile infection
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Fibrosis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
International normalised ratio increased
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Neutropenic sepsis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Peripheral motor neuropathy
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Peripheral swelling
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.0%
4/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Renal failure
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Spinal cord injury
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
White blood cell disorder
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Abdominal pain
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
1.3%
5/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Adrenal insufficiency
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.5%
6/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.3%
5/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Atrial fibrillation
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
2.0%
8/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Hepatobiliary disorders
Autoimmune hepatitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Bronchitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Campylobacter gastroenteritis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Cranial nerve disorder
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Hepatobiliary disorders
Hepatotoxicity
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Hypertension
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Hypophysitis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
3.0%
12/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Infected skin ulcer
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Lipase increased
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Lobar pneumonia
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Malaise
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Motor dysfunction
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Myocardial ischaemia
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Pneumonia klebsiella
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Pyelonephritis acute
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Skin and subcutaneous tissue disorders
Rash morbilliform
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Soft tissue mass
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Urosepsis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.5%
6/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Bacteraemia
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Bandaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Bone marrow disorder
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Coronary artery insufficiency
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Dehydration
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
3.5%
14/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Diarrhoea haemorrhagic
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Eye disorders
Diplopia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Haemorrhage urinary tract
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Hypopituitarism
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Ileus paralytic
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Impaired healing
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
4.0%
8/199 • Day 1 of study therapy to last dose plus 70 days
|
3.0%
12/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Melaena
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Neurological symptom
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Oedema
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Pyrexia
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
3.5%
14/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Spinal cord compression
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Psychiatric disorders
Substance-induced psychotic disorder
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Syncope
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
1.3%
5/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Asthenia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Cystitis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Ear and labyrinth disorders
Deafness
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Device related infection
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Fatigue
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
2.8%
11/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Guillain-Barre syndrome
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Haematuria
|
2.0%
4/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Headache
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Hypotension
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
IVth nerve paresis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Lumbar vertebral fracture
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Lung infiltration
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Meningitis aseptic
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Osteomyelitis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Renal failure acute
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
2.0%
8/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
VIIth nerve paralysis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Weight decreased
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Cerebral thrombosis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Chills
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Clostridium difficile colitis
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Psychiatric disorders
Confusional state
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Constipation
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
1.0%
4/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Generalised oedema
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Haemorrhagic infarction
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Hepatobiliary disorders
Hepatocellular injury
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Herpes virus infection
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Liver function test abnormal
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Megacolon
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Multi-organ failure
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Oedema peripheral
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.75%
3/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.50%
2/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Renal tubular acidosis
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Septic shock
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Spinal cord infection
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
0.00%
0/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Sudden death
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
0.25%
1/399 • Day 1 of study therapy to last dose plus 70 days
|
Other adverse events
| Measure |
PLACEBO
n=199 participants at risk
Placebo infusion (normal saline or 5% dextrose) 2mL/kg was administered intravenously (IV) over 90 minutes. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
10 MG/KG IPILIMUMAB
n=399 participants at risk
Ipilimumab 10 mg/kg was administered intravenously (IV) over 90 minutes with a normal saline flush at the end. Induction dosing occurred on Days 1, 22, 43, and 64 during the Induction phase and every 12 weeks starting at Week 24 during the Maintenance phase until unacceptable toxicity, clinical deterioration, confirmed disease progression, or study closure.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.0%
14/199 • Day 1 of study therapy to last dose plus 70 days
|
5.3%
21/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Diarrhoea
|
24.1%
48/199 • Day 1 of study therapy to last dose plus 70 days
|
47.6%
190/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Pollakiuria
|
5.0%
10/199 • Day 1 of study therapy to last dose plus 70 days
|
4.0%
16/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Infections and infestations
Urinary tract infection
|
7.5%
15/199 • Day 1 of study therapy to last dose plus 70 days
|
7.8%
31/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Vomiting
|
9.0%
18/199 • Day 1 of study therapy to last dose plus 70 days
|
18.8%
75/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Blood and lymphatic system disorders
Anaemia
|
6.0%
12/199 • Day 1 of study therapy to last dose plus 70 days
|
7.8%
31/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.6%
33/199 • Day 1 of study therapy to last dose plus 70 days
|
12.8%
51/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Abdominal pain
|
6.5%
13/199 • Day 1 of study therapy to last dose plus 70 days
|
12.5%
50/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Alanine aminotransferase increased
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
7.8%
31/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
21.1%
42/199 • Day 1 of study therapy to last dose plus 70 days
|
17.3%
69/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Hot flush
|
5.5%
11/199 • Day 1 of study therapy to last dose plus 70 days
|
3.8%
15/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Hypertension
|
3.5%
7/199 • Day 1 of study therapy to last dose plus 70 days
|
6.0%
24/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Aspartate aminotransferase increased
|
1.0%
2/199 • Day 1 of study therapy to last dose plus 70 days
|
6.8%
27/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Dehydration
|
3.0%
6/199 • Day 1 of study therapy to last dose plus 70 days
|
7.8%
31/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Pyrexia
|
9.0%
18/199 • Day 1 of study therapy to last dose plus 70 days
|
15.8%
63/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Asthenia
|
10.1%
20/199 • Day 1 of study therapy to last dose plus 70 days
|
15.3%
61/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Fatigue
|
27.6%
55/199 • Day 1 of study therapy to last dose plus 70 days
|
36.1%
144/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Renal and urinary disorders
Haematuria
|
5.5%
11/199 • Day 1 of study therapy to last dose plus 70 days
|
3.3%
13/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Headache
|
12.1%
24/199 • Day 1 of study therapy to last dose plus 70 days
|
18.3%
73/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Vascular disorders
Hypotension
|
3.0%
6/199 • Day 1 of study therapy to last dose plus 70 days
|
5.3%
21/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/199 • Day 1 of study therapy to last dose plus 70 days
|
6.3%
25/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.5%
11/199 • Day 1 of study therapy to last dose plus 70 days
|
2.0%
8/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
13.6%
27/199 • Day 1 of study therapy to last dose plus 70 days
|
11.3%
45/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Investigations
Weight decreased
|
8.5%
17/199 • Day 1 of study therapy to last dose plus 70 days
|
15.3%
61/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Constipation
|
18.6%
37/199 • Day 1 of study therapy to last dose plus 70 days
|
21.1%
84/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Decreased appetite
|
15.1%
30/199 • Day 1 of study therapy to last dose plus 70 days
|
28.6%
114/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.5%
5/199 • Day 1 of study therapy to last dose plus 70 days
|
6.3%
25/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Oedema peripheral
|
4.5%
9/199 • Day 1 of study therapy to last dose plus 70 days
|
11.0%
44/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
10.6%
21/199 • Day 1 of study therapy to last dose plus 70 days
|
30.8%
123/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.5%
17/199 • Day 1 of study therapy to last dose plus 70 days
|
11.3%
45/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Dizziness
|
8.5%
17/199 • Day 1 of study therapy to last dose plus 70 days
|
9.8%
39/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Psychiatric disorders
Insomnia
|
4.5%
9/199 • Day 1 of study therapy to last dose plus 70 days
|
9.5%
38/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
13.6%
27/199 • Day 1 of study therapy to last dose plus 70 days
|
10.3%
41/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Gastrointestinal disorders
Nausea
|
18.1%
36/199 • Day 1 of study therapy to last dose plus 70 days
|
28.8%
115/399 • Day 1 of study therapy to last dose plus 70 days
|
|
General disorders
Pain
|
8.5%
17/199 • Day 1 of study therapy to last dose plus 70 days
|
6.3%
25/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Eye disorders
Vision blurred
|
0.50%
1/199 • Day 1 of study therapy to last dose plus 70 days
|
5.3%
21/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Nervous system disorders
Dysgeusia
|
3.0%
6/199 • Day 1 of study therapy to last dose plus 70 days
|
5.3%
21/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
4.5%
9/199 • Day 1 of study therapy to last dose plus 70 days
|
8.3%
33/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
5.0%
10/199 • Day 1 of study therapy to last dose plus 70 days
|
2.0%
8/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
4.5%
9/199 • Day 1 of study therapy to last dose plus 70 days
|
6.0%
24/399 • Day 1 of study therapy to last dose plus 70 days
|
|
Skin and subcutaneous tissue disorders
Rash
|
11.1%
22/199 • Day 1 of study therapy to last dose plus 70 days
|
36.3%
145/399 • Day 1 of study therapy to last dose plus 70 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER