Trial Outcomes & Findings for Efficacy and Safety of LBH589B in Adult Patients With Refractory Chronic Myeloid Leukemia in Accelerated or Blast Phase (NCT NCT00449761)

Last Updated: 2021-07-15

Results Overview

The primary efficacy variable was hematologic response, a composite endpoint defined as the overall of complete hematologic response (CHR), and of no evidence of leukemia (NEL) and of the return to chronic phase (RTC).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

From Start of the Study up to Study Termination (approximately up to 18 Months).

Results posted on

2021-07-15

Participant Flow

The study was conducted at 20 centers in 7 countries.

A total 27 Participants were enrolled in the study of which 27 participants discontinued the study treatment and 18 participants discontinued the study.

Participant milestones

Participant milestones
Measure	Panobinostat Participants received panobinostat 20 milligrams (mg) orally once daily (OD), three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 milliliter (ml) of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Overall Study STARTED	27
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Panobinostat Participants received panobinostat 20 milligrams (mg) orally once daily (OD), three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 milliliter (ml) of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Overall Study Disease progression	12
Overall Study Death	5
Overall Study New cancer therapy	1

Baseline Characteristics

Efficacy and Safety of LBH589B in Adult Patients With Refractory Chronic Myeloid Leukemia in Accelerated or Blast Phase

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Age, Continuous	56.6 years STANDARD_DEVIATION 12.38 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	22 Participants n=5 Participants
Race/Ethnicity, Customized Black	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Population: The analysis was performed in Full analysis set (FAS) population was defined according to the intention-to-treat principle. Population included all participants enrolled into the study. Enrolled participant were those who had received at least one dose of study drug. The outcome measure was not achieved as the study was terminated because of a lack of evidence of activity in the targeted participant population.

Outcome measures

Outcome measures
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Participants With Hematologic Response	0 Participants

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. Enrolled patients were those who had received at least one dose of study drug. The outcome measure was not achieved as the study was terminated because of a lack of evidence of activity in the targeted Participant population. Because of a lack of evidence of hematologic response (primary objective), secondary efficacy endpoints were not analyzed.

Duration of hematologic response is defined as the time from the first documentation of the hematologic response to the date of the first documentation of the disease progression

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Durations of complete cytogenetic response is defined as the time from the first documentation of the major/complete response to the first documentation of the disease progression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Durations of major/complete cytogenetic response is defined as the time from the first documentation of the major/complete response to the first documentation of the disease progression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Cytogenetic response was assessed by bone marrow assessment based on the percentage of Ph+ metaphases by karyotype analysis on a bone marrow aspirate, was ideally assessed from a minimum of 20 metaphases in each bone marrow sample.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

The duration of response was defined as the time between the first documented response to the date of discontinuation due to progressive disease (PD) or death.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population included all participants enrolled into the study. Enrolled patients were those who had received at least one dose of study drug. The outcome measure was not achieved as the study was terminated because of a lack of evidence of activity in the targeted Participant population. Due to insufficient data, this outcome could not be measured.

Molecular response was defined as major (≤ 0.1% on the International Scale) and complete \[absence of fusion gene of the BCR and ABL genes (BCR-ABL) on an quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay with a sensitivity of at least 4.5 logs below baseline\].

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Population: The analysis was performed in FAS population was defined according to the intention-to-treat principle. This population included all participants enrolled into the study. Enrolled participants were those who had received at least one dose of study drug. The outcome measure was not achieved as the study was terminated because of a lack of evidence of activity in the targeted Participant population.

A fusion gene of the BCR and ABL genes (BCR-ABL) messenger ribose nucleic acid (mRNA) expression (molecular response) was performed by quantitative polymerase chain reaction (qPCR) and mutational analysis was performed by direct sequencing technology, and both analyses were performed by Genzyme.

Outcome measures

Outcome measures
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
BCR-ABL Mutations of Participants at Study Entry and, in Responding Participants and at the Time of Disease Progression	0 Participants

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Progressions free survival is defined as time between Day 1 cycle 1 and time to first documented disease progression or death. Disease progression will be determined as per response criteria.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Overall survival time is defined as the time from the treatment start to the date of death due to any reason.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Population: The analysis was performed in Pharmacokinetic analysis set (PAS) population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Tmax is defined as the time at which the Cmax occurs. It will be obtained from the Tmax parameter calculated by WinNonlin®. If there is no measurable Cmax in the subject's Pharmacokinetic (PK) profile, then Tmax will be missing for that subject. Tmax will be reported in units of h.

Outcome measures

Outcome measures
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Time to Peak Concentration (Tmax) of Panobinostat Day 1	1.5 Hours Interval 0.2 to 3.4
Time to Peak Concentration (Tmax) of Panobinostat Day 8	1.5 Hours Interval 1.0 to 3.4

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Population: The analysis was performed in PAS population, defined as all participants who provide at least one post-dose PK plasma sample. Here, number of participants analyzed refer to the number of participants evaluable for this outcome at specified time point.

Cmax is defined as the maximum observed drug concentration observed in plasma over all PK sample concentrations. It will be obtained from the Cmax parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Cmax will be missing for that subject. Cmax will be reported in units of ng/mL.

Outcome measures

Outcome measures
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Maximum Plasma Concentration (Cmax) of Panobinostat Day 1	13.5 ng/mL Standard Deviation 7.0
Maximum Plasma Concentration (Cmax) of Panobinostat Day 8	20.9 ng/mL Standard Deviation 15.0

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Area under the curve (AUC) is defined as the area under concentration-time curve as a measure of drug exposure. The area under the plasma concentration-time curve from time zero to 24 hours.

Outcome measures

Outcome measures
Measure	Panobinostat n=12 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Area Under the Plasma Concentration (AUC0-24) of Panobinostat Day 1	139 ng.hr/mL Standard Deviation 61
Area Under the Plasma Concentration (AUC0-24) of Panobinostat Day 8	148 ng.hr/mL Standard Deviation 69

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Clast is defined as the Last observed (quantifiable) plasma concentration (Clast), in units of ng/mL. Blood samples were collected to assess Clast.

Outcome measures

Outcome measures
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Last Observed Plasma Concentration (Clast) of Panobinostat Day 1	1.9 ng/mL Standard Deviation 2.4
Last Observed Plasma Concentration (Clast) of Panobinostat Day 8	4.7 ng/mL Standard Deviation 8.2

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 1-2, and 3-4 hours post dose on Day 1 and Day 8

Time of Clast (Tlast) will be obtained from the Tlast parameter calculated by WinNonlin®. If there is no measurable concentration in the subject's PK profile, then Tlast will be missing for that participants. Tlast will be reported in units of h.

Outcome measures

Outcome measures
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Time of Clast (Tlast) of Panobinostat Day 1	23.9 Hours Interval 3.1 to 49.2
Time of Clast (Tlast) of Panobinostat Day 8	24.1 Hours Interval 2.2 to 27.0

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

QTc monitoring was performed on specified days (Cycle1: Day1, 5 and 26), as well as a single pre-dose ECG once weekly during Cycle1: Week2 and Week3, Cycle2, and all subsequent cycles. Patient eligibility was ensured by a screening QTcF interval calculated by eResearchTechnology(eRT) prior to the baseline assessments. Treatment decisions were based on QTc determined by the automated reading at the investigational site (commonly used the Bazett's correction,QTcB) or measured and calculated by trained personnel at the site. Dosing relied on the investigator's assessment of the 6 baseline ECGs (the average of the 6pre-dose QTc intervals) performed prior to Cycle1/Day1 dosing, of the 3pre-dose ECGs during Cycle1:Day5 and 26, and of the single pre-dose ECGs performed once weekly for the remaining weeks of Cycle1 and subsequent cycles. The Baseline and Change From Baseline to Extreme Value QTcF interval for analysis was calculated by eRT based on the 6 baseline ECGs obtained on Cycle1/Day1.

Outcome measures

Outcome measures
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
QT Interval (QTc) in Participants Receiving Oral Panobinostat at Baseline and Change From Baseline to Extreme Value Baseline	396.6 ms Standard Deviation 20.10
QT Interval (QTc) in Participants Receiving Oral Panobinostat at Baseline and Change From Baseline to Extreme Value Change from Baseline	24.5 ms Standard Deviation 9.58

SECONDARY outcome

Timeframe: From Start of the Study up to Study Termination (approximately up to 18 Months).

Population: The analysis was performed on Safety population consisted of all participants who had received at least one dose of study medication and had one valid post-baseline assessment.

Adverse Events (AE) are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards

Outcome measures

Outcome measures
Measure	Panobinostat n=27 Participants Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day) treatment cycle. Panobinostat was administered at the same time each morning, and with an 8oz/240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Safety and Tolerability of Panobinostat Participants with Adverse Events	27 Participants
Safety and Tolerability of Panobinostat Deaths	16 Participants
Safety and Tolerability of Panobinostat Serious Adverse Events	13 Participants

Adverse Events

Panobinostat

Serious events: 13 serious events

Other events: 27 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	Panobinostat n=27 participants at risk Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day). Panobinostat was administered at the same time each morning, and with an 240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Blood and lymphatic system disorders Febrile neutropenia	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Blood and lymphatic system disorders Haemorrhagic diathesis	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Blood and lymphatic system disorders Neutropenia	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Blood and lymphatic system disorders Thrombocytopenia	14.8% 4/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Asthenia	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Catheter site haemorrhage	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders General physical health deterioration	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Pyrexia	14.8% 4/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Infections and infestations Pneumonia	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Infections and infestations Pseudomonal bacteraemia	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Infections and infestations Sepsis	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Injury, poisoning and procedural complications Post procedural haemorrhage	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Injury, poisoning and procedural complications Subdural haematoma	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Investigations Platelet count decreased	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Investigations White blood cell count increased	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Central nervous system leukaemia	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Nervous system disorders Aphasia	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Nervous system disorders Cerebral haemorrhage	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Nervous system disorders Cerebral infarction	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Nervous system disorders Coma	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Nervous system disorders Haemorrhagic cerebral infarction	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Nervous system disorders Syncope	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Psychiatric disorders Mental status changes	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Renal and urinary disorders Renal failure	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Vascular disorders Thrombophlebitis	3.7% 1/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.

Other adverse events

Other adverse events
Measure	Panobinostat n=27 participants at risk Participants received panobinostat 20 mg orally OD, three times a week as part of a 4 week (28 day). Panobinostat was administered at the same time each morning, and with an 240 ml of water after a fasting period of at least two hours (water was allowed). Participants could continue this treatment until an unacceptable toxicity that precludes further treatment was experienced, or until disease progression.
Blood and lymphatic system disorders Anaemia	37.0% 10/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Blood and lymphatic system disorders Leukocytosis	14.8% 4/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Blood and lymphatic system disorders Neutropenia	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Blood and lymphatic system disorders Thrombocytopenia	37.0% 10/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Cardiac disorders Tachycardia	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Abdominal pain	14.8% 4/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Abdominal pain upper	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Constipation	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Diarrhoea	37.0% 10/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Nausea	22.2% 6/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Stomatitis	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Gastrointestinal disorders Vomiting	14.8% 4/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Asthenia	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Chills	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Fatigue	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Oedema peripheral	14.8% 4/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Pain	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
General disorders Pyrexia	25.9% 7/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Infections and infestations Bacteraemia	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Infections and infestations Pneumonia	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Infections and infestations Upper respiratory tract infection	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Infections and infestations Urinary tract infection	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Investigations White blood cell count increased	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyperkalaemia	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyperuricaemia	18.5% 5/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hypocalcaemia	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hypokalaemia	18.5% 5/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyponatraemia	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Back pain	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Bone pain	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	11.1% 3/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Nervous system disorders Dizziness	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Nervous system disorders Headache	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Renal and urinary disorders Renal failure	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Renal and urinary disorders Urinary incontinence	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.8% 4/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Epistaxis	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	7.4% 2/27 • From Start of the Study up to Study Termination (approximately up to 18 Months). The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place