Trial Outcomes & Findings for Efficacy and Safety Study of Panobinostat in Participants With Metastatic Hormone Refractory Prostate Cancer (NCT NCT00667862)

NCT ID: NCT00667862

Last Updated: 2021-06-21

Results Overview

The PFS rate was defined as the percentage of participants that were alive without documented disease progression at the end of 24 weeks from first study treatment. Disease Progression as per response evaluation criteria in solid tumors (RECIST) criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 centimeter (cm) at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of greater than or equal to (\>=) 2 unequivocal new lesions confirmed on a second scan at least 6 weeks later.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 35 participants
• Primary outcome timeframe: 24 weeks
• Results posted on: 2021-06-21

Participant Flow

A total of 35 participants were enrolled in the study at 8 centers in 2 countries- Canada (3 sites) and the United states (5 sites) from 18 March 2008 to 05 November 2010.

Participant milestones

Measure	Panobinostat Participants with metastatic hormone refractory prostate cancer received 20 milligrams per meter square (mg/m\^2) of panobinostat intravenously (i.v.) on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Overall Study STARTED	35
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	35

Reasons for withdrawal

Measure	Panobinostat Participants with metastatic hormone refractory prostate cancer received 20 milligrams per meter square (mg/m\^2) of panobinostat intravenously (i.v.) on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Overall Study Adverse Event	9
Overall Study Death	1
Overall Study Disease Progression	22
Overall Study Withdrawal by Subject	3

Baseline Characteristics

Efficacy and Safety Study of Panobinostat in Participants With Metastatic Hormone Refractory Prostate Cancer

Baseline characteristics by cohort

Measure	Panobinostat n=35 Participants Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat i.v. on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Age, Continuous	68.1 years STANDARD_DEVIATION 9.41 • n=5 Participants
Sex/Gender, Customized Male	35 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: FAS population included all participants who received at least 1 dose of study drug.

The PFS rate was defined as the percentage of participants that were alive without documented disease progression at the end of 24 weeks from first study treatment. Disease Progression as per response evaluation criteria in solid tumors (RECIST) criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 centimeter (cm) at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of greater than or equal to (>=) 2 unequivocal new lesions confirmed on a second scan at least 6 weeks later.

Outcome measures

Measure	Panobinostat n=35 Participants Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat i.v. on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Percentage of Participants With Progression-Free Survival (PFS) Rate at 24 Weeks	11.4 percentage of participants

SECONDARY outcome

Timeframe: Every 12 weeks up to approximately 2.7 years

Population: FAS population included all participants who received at least 1 dose of study drug.

The tumor response rate was defined as a percentage of participants with confirmed Complete Response (CR) or Partial Response (PR) per RECIST criteria. CR: Disappearance of all target lesions and all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.

Outcome measures

Measure	Panobinostat n=35 Participants Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat i.v. on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Percentage of Participants With Tumor Response Rate	0 percentage of participants

SECONDARY outcome

Timeframe: Every 12 weeks up to approximately 2.7 years

Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.

Duration of SD was the time from date of start of treatment to the date of event, defined as the first documented disease progression or death due to underlying cancer. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of >=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. CR: Disappearance of all target lesions and all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. If a participant had not had an event, duration of SD was to be censored at the date of last assessment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 24 weeks

Population: FAS population included all participants who received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

The PSA response was defined as a 50% decrease in PSA from baseline maintained for >= 4 weeks, and without clinical or radiographic evidence of disease progression during this time period. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of >= 2 unequivocal new lesions confirmed on a second scan at least 6 weeks later.

Outcome measures

Measure	Panobinostat n=34 Participants Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat i.v. on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Percentage of Participants With Prostate Specific Antigen (PSA) Response Rate at 24 Weeks	0 percentage of participants

SECONDARY outcome

Timeframe: 24 weeks

Population: FAS population included all participants who received at least 1 dose of study drug. Overall number of participants analyzed signifies the number of participants who were evaluable for this outcome measure.

The PSA progression was defined as a 50% rise from nadir and a minimum rise of 2 nanogram per milligram (ng/mL). Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of >=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later.

Outcome measures

Measure	Panobinostat n=34 Participants Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat i.v. on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Percentage of Participants With PSA Progression Rate at 24 Weeks	48.6 percentage of participants

SECONDARY outcome

Timeframe: After every cycle up to approximately 2.7 years

Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.

PFS was defined as the time from the date of start of treatment to the date of first documented disease progression or death due to any cause. If a participant had not had a disease progression and was alive, the participant was to be censored using the RECIST. Disease Progression as per RECIST criteria: Measurable lesions: If target lesion was lymph node then it had to be at least 2 cm at baseline to assess change in size. Bone lesions: (non-target lesions) appearance of >=2 unequivocal new lesions confirmed on a second scan at least 6 weeks later. Kaplan-Meier method was to be used to estimate the median PFS.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Start of study treatment to date of death due to any cause (Up to approximately 2.7 years)

Population: We have exhausted all efforts to locate this data and it has since been destroyed, therefore no data is available to report for this outcome measure.

The overall survival was defined as the time from date of start of treatment to date of death due to any cause. If a participant was not known to have died, survival was to be censored at the date of last contact. Kaplan-Meier method was to be used to estimate overall survival.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years)

Population: Safety set population included all participants who were randomized and received at least 1 dose of study drug.

An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.

Outcome measures

Measure	Panobinostat n=35 Participants Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat i.v. on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	35 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	14 Participants

Adverse Events

Panobinostat

Serious events: 14 serious events

Other events: 34 other events

Deaths: 1 deaths

Serious adverse events

Measure	Panobinostat n=35 participants at risk Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat intravenously (i.v.) on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Blood and lymphatic system disorders Anaemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Cardiac disorders Angina pectoris	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Cardiac disorders Atrial fibrillation	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Constipation	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Nausea	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Vomiting	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Asthenia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Sepsis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Urosepsis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Blood creatinine increased	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Electrocardiogram QT prolonged	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Platelet count decreased	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Dehydration	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypokalaemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hyponatraemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypophagia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypophosphataemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Arthralgia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Bone pain	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Muscular weakness	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Spinal cord compression	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Transient ischaemic attack	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Anuria	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Haematuria	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Renal failure	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Renal failure acute	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Ureteric obstruction	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Vascular disorders Hypotension	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.

Other adverse events

Measure	Panobinostat n=35 participants at risk Participants with metastatic hormone refractory prostate cancer received 20 mg/m\^2 of panobinostat intravenously (i.v.) on Days 1 and 8 of a 21-day cycle. Treatment continued until disease progression as per investigator, intolerable toxicity, start of new cancer therapy, death, or withdrawal of consent.
Blood and lymphatic system disorders Anaemia	17.1% 6/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Blood and lymphatic system disorders Leukocytosis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Blood and lymphatic system disorders Leukopenia	11.4% 4/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Blood and lymphatic system disorders Lymphopenia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Blood and lymphatic system disorders Neutropenia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Blood and lymphatic system disorders Thrombocytopenia	45.7% 16/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Cardiac disorders Atrial fibrillation	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Cardiac disorders Cardio-respiratory arrest	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Cardiac disorders Palpitations	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Cardiac disorders Tachycardia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Endocrine disorders Hyperthyroidism	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Endocrine disorders Hypothyroidism	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Eye disorders Conjunctival haemorrhage	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Eye disorders Dry eye	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Eye disorders Vision blurred	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Abdominal discomfort	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Abdominal distension	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Abdominal pain	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Abdominal pain lower	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Aphthous stomatitis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Constipation	22.9% 8/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Diarrhoea	34.3% 12/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Dry mouth	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Dysphagia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Flatulence	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Gastritis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Nausea	51.4% 18/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Paraesthesia oral	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Gastrointestinal disorders Vomiting	31.4% 11/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Asthenia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Axillary pain	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Catheter site pain	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Chills	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Fatigue	62.9% 22/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Feeling cold	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Gait disturbance	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Infusion site extravasation	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Non-cardiac chest pain	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Oedema peripheral	11.4% 4/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Pain	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
General disorders Pyrexia	14.3% 5/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Hepatobiliary disorders Hyperbilirubinaemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Immune system disorders Food allergy	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Immune system disorders Hypersensitivity	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Candidiasis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Cystitis	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Device related infection	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Escherichia infection	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Gastroenteritis viral	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Infected cyst	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Lung infection	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Nasopharyngitis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Oral herpes	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Sepsis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Sinusitis	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Upper respiratory tract infection	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Infections and infestations Urinary tract infection	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Injury, poisoning and procedural complications Contusion	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Activated partial thromboplastin time prolonged	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Alanine aminotransferase increased	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Aspartate aminotransferase increased	14.3% 5/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Blood creatine increased	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Blood creatinine increased	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Blood magnesium decreased	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Blood phosphorus decreased	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Blood potassium decreased	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Blood triglycerides increased	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Electrocardiogram QT prolonged	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Electrocardiogram ST segment abnormal	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Electrocardiogram T wave inversion	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Haemoglobin decreased	17.1% 6/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations High density lipoprotein decreased	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations International normalised ratio increased	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Platelet count decreased	11.4% 4/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Transaminases increased	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Investigations Weight decreased	31.4% 11/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Decreased appetite	37.1% 13/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Dehydration	14.3% 5/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Diabetes mellitus	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hyperglycaemia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hyperkalaemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypermagnesaemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hyperphosphataemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypertriglyceridaemia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hyperuricaemia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypocalcaemia	14.3% 5/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypokalaemia	11.4% 4/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypomagnesaemia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hyponatraemia	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Metabolism and nutrition disorders Hypophosphataemia	17.1% 6/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 7/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Back pain	31.4% 11/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Bone pain	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Coccydynia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Flank pain	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Muscle spasms	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Muscular weakness	11.4% 4/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Neck pain	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Musculoskeletal and connective tissue disorders Pain in extremity	11.4% 4/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic pain	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Dizziness	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Dysgeusia	28.6% 10/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Headache	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Hypoaesthesia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Neuropathy peripheral	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Paraesthesia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Peripheral sensory neuropathy	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Post herpetic neuralgia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Vascular disorders Flushing	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Presyncope	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Somnolence	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Syncope	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Nervous system disorders Tremor	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Psychiatric disorders Anxiety	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Psychiatric disorders Insomnia	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Dysuria	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Haematuria	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Nocturia	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Urinary hesitation	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Urinary incontinence	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Renal and urinary disorders Urinary retention	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Reproductive system and breast disorders Penile discharge	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Reproductive system and breast disorders Penile haemorrhage	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Cough	5.7% 2/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.6% 3/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Hiccups	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Oropharyngeal blistering	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Respiratory, thoracic and mediastinal disorders Sinus congestion	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Skin and subcutaneous tissue disorders Dermal cyst	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Skin and subcutaneous tissue disorders Erythema	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Skin and subcutaneous tissue disorders Hyperhidrosis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Skin and subcutaneous tissue disorders Night sweats	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Skin and subcutaneous tissue disorders Petechiae	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Skin and subcutaneous tissue disorders Pruritus	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Skin and subcutaneous tissue disorders Rash	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Skin and subcutaneous tissue disorders Rash erythematous	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Vascular disorders Deep vein thrombosis	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Vascular disorders Hypertension	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Vascular disorders Hypotension	14.3% 5/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Vascular disorders Orthostatic hypotension	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.
Vascular disorders Peripheral coldness	2.9% 1/35 • From start of the study up to at least 4 weeks following the last dose of study treatment (Up to approximately 2.7 years) An AE was an adverse medical event which occurs in a participant of the study and which is not necessarily in a causal relationship with the treatment the participant receives. SAEs were AEs leading to death, are life-threatening, require hospitalizations or prolongation of hospitalizations, represent an innate malformation or a congenital abnormality.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

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 the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER