Trial Outcomes & Findings for A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation (NCT NCT01572727)
NCT ID: NCT01572727
Last Updated: 2017-03-09
Results Overview
PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
416 participants
Primary outcome timeframe
Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed
Results posted on
2017-03-09
Participant Flow
416 patients randomized patients, 405 received the study treatment \& 403 had at least 1 post-baseline safety assessment. Randomization of patients was stopped following DMC decision \& all but 5 still benefiting from the treatment were discontinued. The DMC decision was based on pre-defined futility criteria at time of the adaptive interim analysis.
A total of approximately 524 patients were to be randomized in a 1:1 ratio to one of the two treatment arms irrespective of the adaptation decision to continue in the full or PI3K pathway activated subpopulation. Randomization was stratified by PI3K activation and Hormone Receptor status.
Participant milestones
| Measure |
BKM120 and Paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo and Paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
|---|---|---|
|
Overall Study
STARTED
|
207
|
209
|
|
Overall Study
Pts With Treatment + Safety Assessment
|
202
|
201
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
207
|
209
|
Reasons for withdrawal
| Measure |
BKM120 and Paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo and Paclitaxel
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
|---|---|---|
|
Overall Study
Adverse Event
|
43
|
15
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
|
Overall Study
Physician Decision
|
23
|
9
|
|
Overall Study
Progressive disease
|
59
|
82
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Study terminated by sponsor
|
61
|
83
|
|
Overall Study
Parent/guardian decision
|
14
|
9
|
|
Overall Study
Death
|
2
|
2
|
|
Overall Study
Untreated
|
4
|
7
|
Baseline Characteristics
A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation
Baseline characteristics by cohort
| Measure |
BKM120 and Paclitaxel
n=207 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo and Paclitaxel
n=209 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
Total
n=416 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
54.1 Years
STANDARD_DEVIATION 11.13 • n=5 Participants
|
55.6 Years
STANDARD_DEVIATION 10.48 • n=7 Participants
|
54.9 Years
STANDARD_DEVIATION 10.89 • n=5 Participants
|
|
Sex: Female, Male
Female
|
207 Participants
n=5 Participants
|
209 Participants
n=7 Participants
|
416 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzedPopulation: FAS per Expert Report: All pts randomized to study treatment. Per ITT principle, pts were analyzed according to treatment \& strata. FAS was primary population for analysis of efficacy endpoints at interim. 338 pts were randomized (between 16-Aug-2012 \& 07-Jun-2014) in 1:1 ratio to buparlisib + paclitaxel arm N=168 or placebo + paclitaxel arm N=170.
PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Outcome measures
| Measure |
BKM120 and Paclitaxel
n=168 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo and Paclitaxel
n=170 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
|---|---|---|
|
Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll)
|
8.0 Months
Interval 7.2 to 9.2
|
9.2 Months
Interval 7.3 to 11.0
|
SECONDARY outcome
Timeframe: every 3 months until death, lost to follow-up, or withdrawal of consent to survival follow-up, up to 10 months after futility was analyzedPopulation: Full analysis set (FAS) comprises all patients who were randomized to study treatment.
Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last contact.
Outcome measures
| Measure |
BKM120 and Paclitaxel
n=207 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo and Paclitaxel
n=209 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
|---|---|---|
|
Overall Survival by Kaplan-Meier Estimate (Phase ll)
|
29.5 Months
Interval 25.0 to 30.0
|
NA Months
N/A = Given the fact that patients were discontinued after the interim analysis the number of participants with events was too low to analyze.
|
SECONDARY outcome
Timeframe: every 8 weeks after randomization Up to 3 months after end of TreatmentPopulation: FAS per Expert Report: All pts randomized to study treatment. Per ITT principle, pts were analyzed according to treatment \& strata. FAS was primary population for analysis of efficacy endpoints at interim. 338 pts were randomized (between 16-Aug-2012 \& 07-Jun-2014) in 1:1 ratio to buparlisib + paclitaxel arm N=168 or placebo + paclitaxel arm N=170.
Percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1. According to this criteria, CR = at least two determinations of CR at least 4 weeks apart before progression; PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Outcome measures
| Measure |
BKM120 and Paclitaxel
n=168 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo and Paclitaxel
n=170 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
|---|---|---|
|
Overall Response Rate (Phase ll)
|
22.6 Percentage of participants
Interval 16.5 to 29.7
|
27.1 Percentage of participants
Interval 20.5 to 34.4
|
SECONDARY outcome
Timeframe: every 8 weeks after randomization Up to 3 months after end of TreatmentPopulation: PFS, ORR and CBR were analyzed and reported at the interim analysis. Given the study met the futility analysis per protocol, the duration of response was removed as a secondary endpoint in the final analysis and consequently not analyzed.
time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: every 8 weeks after randomization Up to 3 months after end of TreatmentPopulation: PFS, ORR and CBR were analyzed and reported at the interim analysis. Given the study met the futility analysis per protocol, time to response was removed as a secondary endpoint in the final analysis and consequently not analyzed.
time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: every 8 weeks after randomization Up to 3 months after end of TreatmentPopulation: FAS per Expert Report: All pts randomized to study treatment. Per ITT principle, pts were analyzed according to treatment \& strata. FAS was primary population for analysis of efficacy endpoints at interim. 338 pts were randomized (between 16-Aug-2012 \& 07-Jun-2014) in 1:1 ratio to buparlisib + paclitaxel arm N=168 or placebo + paclitaxel arm N=170.
CBR was defined as the percentage of patients with an overall response of CR or PR or SD or non-CR/non-PD lasting more than 24 weeks based on local Investigator's assessment according to RECIST v1.1.
Outcome measures
| Measure |
BKM120 and Paclitaxel
n=168 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo and Paclitaxel
n=170 Participants
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
|---|---|---|
|
Clinical Benefit Rate (CBR) (Phase ll)
|
26.2 Percentage of participants
Interval 19.7 to 33.5
|
32.9 Percentage of participants
Interval 25.9 to 40.6
|
SECONDARY outcome
Timeframe: Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1.Population: PFS, ORR and CBR were analyzed and reported at the interim analysis. Given the study met the futility analysis per protocol, the plasma concentration-time profiles was removed as a secondary endpoint in the final analysis and consequently not analyzed.
Summary statistics for PK: plasma concentration-time profiles of BKM120 and appropriate individual PK parameters based on population PK model , if deemed appropriate; each cycle = 28 days
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: every 4 weeksPopulation: PFS, ORR and CBR were analyzed and reported at the interim analysis. Given the study met the futility analysis per protocol, the time to definitive deterioration of ECOG performance status was removed as a secondary endpoint in the final analysis and consequently not analyzed.
Time to definitive deterioration of the ECOG performance status from baseline
Outcome measures
Outcome data not reported
Adverse Events
Buparlisib (BKM120) 100 mg Plus Paclitaxel 80 mg Per m2
Serious events: 61 serious events
Other events: 196 other events
Deaths: 0 deaths
Placebo 100 mg Plus Paclitaxel 80 mg Per m2
Serious events: 42 serious events
Other events: 188 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Buparlisib (BKM120) 100 mg Plus Paclitaxel 80 mg Per m2
n=202 participants at risk
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo 100 mg Plus Paclitaxel 80 mg Per m2
n=201 participants at risk
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
|---|---|---|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Cardiac disorders
CARDIO-RESPIRATORY ARREST
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Eye disorders
CATARACT
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Eye disorders
OPTIC NEUROPATHY
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
DIARRHOEA
|
2.5%
5/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
1.5%
3/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
NAUSEA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
PANCREATITIS
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
VOMITING
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
ASTHENIA
|
1.5%
3/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
FACE OEDEMA
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
1.5%
3/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
LOCALISED OEDEMA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
MALAISE
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
PYREXIA
|
3.5%
7/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
1.5%
3/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Hepatobiliary disorders
CHOLECYSTITIS
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Immune system disorders
ANAPHYLACTIC REACTION
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Immune system disorders
HYPERSENSITIVITY
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
ABSCESS LIMB
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
CELLULITIS
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
2.5%
5/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
DEVICE RELATED INFECTION
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
1.00%
2/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
GASTROINTESTINAL INFECTION
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
HERPES ZOSTER
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
INFLUENZA
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
INFUSION SITE INFECTION
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
MENINGITIS
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
PNEUMOCYSTIS JIROVECII INFECTION
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
PNEUMONIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
PYELONEPHRITIS
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
SEPSIS
|
1.5%
3/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
STAPHYLOCOCCAL BACTERAEMIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
URINARY TRACT INFECTION
|
2.0%
4/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Injury, poisoning and procedural complications
FALL
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Injury, poisoning and procedural complications
FEMUR FRACTURE
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Injury, poisoning and procedural complications
HEAD INJURY
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Injury, poisoning and procedural complications
POST-TRAUMATIC PAIN
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Injury, poisoning and procedural complications
SPINAL FRACTURE
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Injury, poisoning and procedural complications
TOXICITY TO VARIOUS AGENTS
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Injury, poisoning and procedural complications
ULNA FRACTURE
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
EJECTION FRACTION DECREASED
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
LYMPHOCYTE COUNT INCREASED
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
1.5%
3/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
HYPOGLYCAEMIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
1.00%
2/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
PATHOLOGICAL FRACTURE
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CANCER PAIN
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASES TO CENTRAL NERVOUS SYSTEM
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
ALTERED STATE OF CONSCIOUSNESS
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
BRACHIAL PLEXOPATHY
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
BRAIN COMPRESSION
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
BRAIN OEDEMA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
CEREBRAL HAEMORRHAGE
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
ENCEPHALOPATHY
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
HEMIPARESIS
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
METABOLIC ENCEPHALOPATHY
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
PARAESTHESIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
SEIZURE
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
SPINAL CORD COMPRESSION
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
SYNCOPE
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
1.00%
2/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
ACUTE PSYCHOSIS
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
ANXIETY
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
DELIRIUM
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
DEPRESSION
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
MENTAL DISORDER
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
MENTAL STATUS CHANGES
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
PSYCHOTIC DISORDER
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Renal and urinary disorders
ACUTE KIDNEY INJURY
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Renal and urinary disorders
RENAL FAILURE
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Reproductive system and breast disorders
BREAST HAEMORRHAGE
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Reproductive system and breast disorders
BREAST ULCERATION
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
ASTHMA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
1.00%
2/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
INTERSTITIAL LUNG DISEASE
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
3.0%
6/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMOTHORAX
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
RASH MACULAR
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
RASH PRURITIC
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
SKIN MASS
|
0.00%
0/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
SWELLING FACE
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
TOXIC SKIN ERUPTION
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
URTICARIA
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Social circumstances
DIET NONCOMPLIANCE
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Vascular disorders
DEEP VEIN THROMBOSIS
|
1.5%
3/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Vascular disorders
HYPERTENSION
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Vascular disorders
VENA CAVA THROMBOSIS
|
0.50%
1/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.00%
0/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Vascular disorders
VENOUS THROMBOSIS
|
0.99%
2/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
0.50%
1/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
Other adverse events
| Measure |
Buparlisib (BKM120) 100 mg Plus Paclitaxel 80 mg Per m2
n=202 participants at risk
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel
|
Placebo 100 mg Plus Paclitaxel 80 mg Per m2
n=201 participants at risk
Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel
|
|---|---|---|
|
Blood and lymphatic system disorders
ANAEMIA
|
22.8%
46/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
25.4%
51/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
31.7%
64/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
26.9%
54/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Eye disorders
LACRIMATION INCREASED
|
5.9%
12/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
8.5%
17/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Eye disorders
VISION BLURRED
|
9.4%
19/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
3.5%
7/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
13.4%
27/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
10.9%
22/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
5.4%
11/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
7.0%
14/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
CONSTIPATION
|
23.3%
47/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
18.9%
38/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
DIARRHOEA
|
54.0%
109/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
33.8%
68/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
DRY MOUTH
|
5.9%
12/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
5.0%
10/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
DYSPEPSIA
|
11.4%
23/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
7.5%
15/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
NAUSEA
|
41.1%
83/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
25.4%
51/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
STOMATITIS
|
27.7%
56/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
11.9%
24/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Gastrointestinal disorders
VOMITING
|
19.3%
39/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
14.9%
30/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
ASTHENIA
|
23.8%
48/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
22.4%
45/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
FATIGUE
|
33.2%
67/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
31.8%
64/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
2.0%
4/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
5.5%
11/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
OEDEMA PERIPHERAL
|
10.4%
21/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
24.9%
50/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
PAIN
|
4.5%
9/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
5.5%
11/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
General disorders
PYREXIA
|
14.4%
29/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
9.5%
19/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
RHINITIS
|
5.4%
11/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
4.5%
9/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
5.4%
11/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
11.4%
23/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Infections and infestations
URINARY TRACT INFECTION
|
8.9%
18/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
9.0%
18/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
17.3%
35/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
6.0%
12/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
14.9%
30/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
5.5%
11/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
BLOOD GLUCOSE INCREASED
|
6.4%
13/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
5.0%
10/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
GAMMA-GLUTAMYLTRANSFERASE INCREASED
|
3.5%
7/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
6.0%
12/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
NEUTROPHIL COUNT DECREASED
|
7.4%
15/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
7.5%
15/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
WEIGHT DECREASED
|
14.9%
30/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
7.0%
14/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Investigations
WHITE BLOOD CELL COUNT DECREASED
|
5.0%
10/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
7.0%
14/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
31.7%
64/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
12.9%
26/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
40.6%
82/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
10.9%
22/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
9.4%
19/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
3.0%
6/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
11.4%
23/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
15.9%
32/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
10.4%
21/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
10.9%
22/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
5.0%
10/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
7.0%
14/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
4.0%
8/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
6.0%
12/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
10.9%
22/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
13.4%
27/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
13.4%
27/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
19.9%
40/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
DIZZINESS
|
16.3%
33/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
10.4%
21/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
DYSGEUSIA
|
19.3%
39/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
16.9%
34/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
HEADACHE
|
17.3%
35/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
18.4%
37/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
NEUROPATHY PERIPHERAL
|
24.8%
50/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
23.9%
48/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
PARAESTHESIA
|
12.4%
25/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
16.9%
34/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Nervous system disorders
PERIPHERAL SENSORY NEUROPATHY
|
15.3%
31/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
15.4%
31/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
ANXIETY
|
20.3%
41/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
15.4%
31/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
DEPRESSION
|
24.8%
50/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
8.5%
17/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
INSOMNIA
|
15.3%
31/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
16.4%
33/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Psychiatric disorders
MOOD ALTERED
|
5.4%
11/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
2.5%
5/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
19.8%
40/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
13.9%
28/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
12.9%
26/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
10.4%
21/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
14.4%
29/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
16.4%
33/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
5.9%
12/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
8.0%
16/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
51.0%
103/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
51.7%
104/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
13.9%
28/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
6.5%
13/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
5.4%
11/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
8.5%
17/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
NAIL DISCOLOURATION
|
3.5%
7/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
7.0%
14/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
NAIL DISORDER
|
3.5%
7/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
9.5%
19/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
ONYCHOMADESIS
|
3.5%
7/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
5.5%
11/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
15.8%
32/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
14.9%
30/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
RASH
|
42.6%
86/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
21.4%
43/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Skin and subcutaneous tissue disorders
RASH MACULO-PAPULAR
|
5.9%
12/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
4.0%
8/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Vascular disorders
FLUSHING
|
3.5%
7/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
5.5%
11/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Vascular disorders
HYPERTENSION
|
8.4%
17/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
5.0%
10/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
|
Vascular disorders
LYMPHOEDEMA
|
3.5%
7/202
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
8.0%
16/201
Among 416 randomized patients, 405 patients received the study treatment. Of them, 403 patients had at least one post-baseline safety assessment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER