Trial Outcomes & Findings for Ixabepilone + Carboplatin Metastatic Breast Cancer (NCT NCT01075100)

Last Updated: 2016-12-07

Results Overview

Evaluate the objective response rate calculated as CR+ PR in the population evaluable for response, as well as the 2 subgroups (hormone receptor positive \[ER+/PR+/HER2-, ER+/PR-/HER2-, ER-/PR+/HER2-\]) and ER-/PR-HER2-, separately). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

103 participants

Primary outcome timeframe

24 months

Results posted on

2016-12-07

Participant Flow

Participant milestones

Participant milestones
Measure	Triple Negative ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received receive Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Overall Study STARTED	49	54
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	49	53

Reasons for withdrawal

Reasons for withdrawal
Measure	Triple Negative ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received receive Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Overall Study Adverse Event	15	18
Overall Study Patient Request	4	4
Overall Study Investigator Request	2	1
Overall Study Disease Progression	25	29
Overall Study Other	3	1

Baseline Characteristics

Ixabepilone + Carboplatin Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Triple Negative n=49 Participants ER-/PR-/HER2- patients who received receive Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=54 Participants ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received receive Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	Total n=103 Participants Total of all reporting groups
Age, Continuous	55.0 years STANDARD_DEVIATION 9.0 • n=5 Participants	56.7 years STANDARD_DEVIATION 10.6 • n=7 Participants	55.9 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	54 Participants n=7 Participants	103 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	33 participants n=5 Participants	39 participants n=7 Participants	72 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Hawaiian	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black	14 participants n=5 Participants	10 participants n=7 Participants	24 participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment United States	49 participants n=5 Participants	54 participants n=7 Participants	103 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: Evaluable population

Outcome measures

Outcome measures
Measure	Triple Negative n=46 Participants ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=53 Participants ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Objective Response Rate (ORR)	30.4 percentage of participants Interval 17.7 to 45.8	34 percentage of participants Interval 21.5 to 48.3

SECONDARY outcome

Timeframe: 24 months

Population: Evaluable population

Clinical benefit rate (CBR) defined as objective response rate (ORR, CR + PR) + SD \>= 6 months

Outcome measures

Outcome measures
Measure	Triple Negative n=46 Participants ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=53 Participants ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Clinical Benefit Rate (CBR)	41.3 percentage of participants Interval 27.0 to 56.8	56.6 percentage of participants Interval 42.3 to 70.2

SECONDARY outcome

Timeframe: 24 months

Population: ITT population

PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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

Outcome measures
Measure	Triple Negative n=49 Participants ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=54 Participants ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Progression-free Survival (PFS)	7.6 months Interval 4.3 to 8.4	7.6 months Interval 4.2 to 9.8

SECONDARY outcome

Timeframe: 24 months

Population: ITT population

OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date.

Outcome measures

Outcome measures
Measure	Triple Negative n=49 Participants ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=54 Participants ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Overall Survival (OS)	12.5 months Interval 10.2 to 14.2	17.9 months Interval 14.4 to 22.4

SECONDARY outcome

Timeframe: 24 months

Population: Patients who achieve a major objective response (CR or PR).

For patients who achieve a major objective response (CR or PR) the time to response will be assessed as the date of registration to the date of response.

Outcome measures

Outcome measures
Measure	Triple Negative n=14 Participants ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=18 Participants ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Time to Response	1.27 months Interval 0.92 to 3.98	1.60 months Interval 1.12 to 8.95

SECONDARY outcome

Timeframe: 30 months

Population: Patients who achieved CR or PR.

The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented.

Outcome measures

Outcome measures
Measure	Triple Negative n=14 Participants ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=18 Participants ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Duration of Response	6.68 months Interval 2.43 to 20.4	5.92 months Interval 1.84 to 25.6

Adverse Events

Triple Negative

Serious events: 10 serious events

Other events: 44 other events

Deaths: 0 deaths

HR Positive

Serious events: 5 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Cynthia Osborne

US Oncology Research, McKesson Specialty Health

Phone: 214-370-1057

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Triple Negative n=48 participants at risk ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=53 participants at risk ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Gastrointestinal disorders ABDOMINAL PAIN	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders APPETITE DECREASED	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Infections and infestations BACTERIAL RESISTANCE	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DEHYDRATION	8.3% 4/48 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DIARRHEA	8.3% 4/48 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders DIZZINESS	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Respiratory, thoracic and mediastinal disorders EMBOLISM PULMONARY	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders FEVER	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Cardiac disorders FIBRILLATION ATRIAL	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOKALEMIA	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPONATREMIA	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Cardiac disorders HYPOTENSION	2.1% 1/48 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders NAUSEA	6.2% 3/48 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders NEUTROPENIA	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Respiratory, thoracic and mediastinal disorders PNEUMONIA	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Renal and urinary disorders RENAL INSUFFICIENCY	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Respiratory, thoracic and mediastinal disorders RESPIRATION RATE DECREASED	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders RIGORS	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Infections and infestations SEPSIS	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Respiratory, thoracic and mediastinal disorders SHORTNESS OF BREATH	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders THROMBOCYTOPENIA	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders VOLUME BLOOD DECREASED	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders VOMITING	4.2% 2/48 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders WEAKNESS GENERALIZED	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.

Measure	Triple Negative n=48 participants at risk ER-/PR-/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.	HR Positive n=53 participants at risk ER+/PR+/HER2-, or ER+/PR-/HER2-, or ER-/PR+/HER2- patients who received Ixabepilone 20 mg/m2 on Days 1 and 8 and Carboplatin AUC=2.5 on Days 1 and 8 of each 21-day cycle.
Gastrointestinal disorders NAUSEA	47.9% 23/48 • Number of events 40 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	58.5% 31/53 • Number of events 47 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders NEUROPATHY	45.8% 22/48 • Number of events 35 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	50.9% 27/53 • Number of events 51 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders NEUTROPENIA	64.6% 31/48 • Number of events 99 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	73.6% 39/53 • Number of events 184 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders PAIN	4.2% 2/48 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	9.4% 5/53 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Musculoskeletal and connective tissue disorders PAIN BACK	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.7% 3/53 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders RASH	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	9.4% 5/53 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders THROMBOCYTOPENIA	33.3% 16/48 • Number of events 44 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	47.2% 25/53 • Number of events 65 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders VOMITING	16.7% 8/48 • Number of events 12 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	35.8% 19/53 • Number of events 26 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders WEAKNESS	8.3% 4/48 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	3.8% 2/53 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders WEIGHT LOSS	6.2% 3/48 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.7% 3/53 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders ABDOMINAL PAIN	12.5% 6/48 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	9.4% 5/53 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Immune system disorders ALLERGIC REACTION	6.2% 3/48 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	9.4% 5/53 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders ALOPECIA	31.2% 15/48 • Number of events 16 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	37.7% 20/53 • Number of events 22 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders ANEMIA	56.2% 27/48 • Number of events 58 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	52.8% 28/53 • Number of events 103 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders ANOREXIA	12.5% 6/48 • Number of events 8 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	24.5% 13/53 • Number of events 18 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Musculoskeletal and connective tissue disorders ARTHRALGIA	0.00% 0/48 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	7.5% 4/53 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders CHILLS	6.2% 3/48 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	0.00% 0/53 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders CONSTIPATION	12.5% 6/48 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	24.5% 13/53 • Number of events 17 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DEHYDRATION	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	13.2% 7/53 • Number of events 12 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DIARRHEA	27.1% 13/48 • Number of events 18 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	28.3% 15/53 • Number of events 22 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Nervous system disorders DIZZINESS	4.2% 2/48 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	7.5% 4/53 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DYSGUESIA	12.5% 6/48 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	15.1% 8/53 • Number of events 12 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders DYSPEPSIA	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.7% 3/53 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders EDEMA	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.7% 3/53 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders FATIGUE	37.5% 18/48 • Number of events 29 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	58.5% 31/53 • Number of events 58 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
General disorders FEVER	6.2% 3/48 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.7% 3/53 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Gastrointestinal disorders GASTROESOPHAGEAL REFLUX	4.2% 2/48 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.7% 3/53 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOKALEMIA	6.2% 3/48 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.7% 3/53 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	6.2% 3/48 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Blood and lymphatic system disorders LEUCOPENIA	12.5% 6/48 • Number of events 13 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	26.4% 14/53 • Number of events 58 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Infections and infestations MUCOSITIS	2.1% 1/48 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	5.7% 3/53 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Musculoskeletal and connective tissue disorders MUSCLE WEAKNESS	6.2% 3/48 • Number of events 8 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	1.9% 1/53 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Musculoskeletal and connective tissue disorders MYALGIA	4.2% 2/48 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	9.4% 5/53 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders NAIL DISORDER	6.2% 3/48 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.	11.3% 6/53 • Number of events 7 • During the whole treatment period, up to 30 days following last dose. For treated patients only, assessed at each treatment visit.