Trial Outcomes & Findings for Eltrombopag in Combination With Rabbit Anti-thymocyte Globulin/Cyclosporine A in Naive Aplastic Anemia (AA) Subjects (NCT NCT02404025)

Last Updated: 2019-07-26

Results Overview

ORR will be calculated after 6 months of eltrombopag administration by measuring platelet, reticulocyte, neutrophil and transfusion independence. ORR includes Complete Response (CR) and Partial Response (PR) Rate.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Week 26

Results posted on

2019-07-26

Participant Flow

10 subject started eltrombopag, and 1 subject was withdrawn from the study before starting eltrombopag, as he did not meet the eligibility criteria prior to receiving eltrombopag.

Participant milestones

Participant milestones
Measure	Eltrombopag+Rabbit ATG/CsA Arm Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Overall Study STARTED	10
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Eltrombopag+Rabbit ATG/CsA Arm Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	3

Baseline Characteristics

per protocol set

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Age, Continuous	55.5 years n=5 Participants • per protocol set
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian Japanese	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 26

Population: Full analysis set; population obtained by excluding subjects: Eltrombopag was never administered to the subject during the study, subject had no baseline data: platelet count, hemoglobin, neutrophil count, and transfusion,subject had no data after the start of rabbit ATG therapy: platelet count, hemoglobin, neutrophil count, and transfusion.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
ORR at 6 Months: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26 CR+PR	7 Participants
ORR at 6 Months: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26 CR	0 Participants
ORR at 6 Months: Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at Week 26 PR	7 Participants

SECONDARY outcome

Timeframe: Week 14

ORR will be calculated after 3 months of eltrombopag administration by measuring platelet, reticulocyte, neutrophil and transfusion independence.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
ORR at 3 Months	2 Participants

SECONDARY outcome

Timeframe: Week 14

CR and PR will be calculated after 3 months of eltrombopag administration by measuring platelet, reticulocyte, neutrophil and transfusion independence.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Complete Response (CR), and Partial Response (PR) Rate at 3 Months CR	0 Participants
Complete Response (CR), and Partial Response (PR) Rate at 3 Months PR	2 Participants

SECONDARY outcome

Timeframe: Week 26

CR criteria used in NIH 12-H-150 study is as follows: Hemoglobin \>10 gram (g)/ deciliter (dL), and Absolute neutrophil count (ANC) \>1,000/microliter, and Platelets \>100,000/microliter.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
CR Rate Based on the Criteria Used in NIH 12-H-0150 Study at 6 Months	1 Participants

SECONDARY outcome

Timeframe: Week 26 and week 104

The change in hematology values ( haemoglobin) were evaluated.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Changes in Hematology Parameters (Haemoglobin) in the Absence of Platelet Transfusion Haemoglobin changes from baseline, week 26 (g/L)	24.6 g/L Standard Deviation 19.20
Changes in Hematology Parameters (Haemoglobin) in the Absence of Platelet Transfusion Haemoglobin changes from baseline, week 104 (g/L)	39.0 g/L Standard Deviation 3.61

SECONDARY outcome

Timeframe: Week 26 and week 104

The change in hematology values from baseline for platelets, neutrophils and reticulocytes were evaluated.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Changes in Hematology Parameters in the Absence of Platelet Transfusion reticulocytes changes from baseline week104 (Gi/L)	48.0900 Gi/L Standard Deviation 29.96719
Changes in Hematology Parameters in the Absence of Platelet Transfusion neutrophils changes from baseline, week 26 (Gi/L)	1.2196 Gi/L Standard Deviation 0.59501
Changes in Hematology Parameters in the Absence of Platelet Transfusion neutrophils changes from baseline, week 104 (Gi/L)	1.2978 Gi/L Standard Deviation 0.65819
Changes in Hematology Parameters in the Absence of Platelet Transfusion platelets changes from baseline, week 26 (Gi/L)	66.94 Gi/L Standard Deviation 57.187
Changes in Hematology Parameters in the Absence of Platelet Transfusion platelets changes from baseline, week 104 (Gi/L)	107.33 Gi/L Standard Deviation 4.041
Changes in Hematology Parameters in the Absence of Platelet Transfusion reticulocytes changes from baseline week 26 (Gi/L)	30.0175 Gi/L Standard Deviation 21.81519

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: full analysis set, participants who were transfusion dependant

RBC transfusion dependency defined as at least one RBC transfusion within 8 weeks prior to D1. Platelet or RBC transfusions will be based on physician's subjective judgement. Platelet transfusion will be done if the platelet count is less than 10×10\^9/liter (L) with significant bleeding tendency or the platelet count is less than 20×10\^9/L with pyrexia. RBC transfusion will be done to keep the hemoglobin concentration at over 7 g/dL or in the presence of clinical symptoms such as dyspnea.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Frequency of Platelet and Red Blood Cells (RBC) Transfusions Baseline RBC transfusions	4.0 mean of transfusions number Standard Deviation 3.10
Frequency of Platelet and Red Blood Cells (RBC) Transfusions Week 26 RBC transfusions	1.0 mean of transfusions number Standard Deviation 2.24
Frequency of Platelet and Red Blood Cells (RBC) Transfusions Baseline Platelet transfusion	3.4 mean of transfusions number Standard Deviation 2.77
Frequency of Platelet and Red Blood Cells (RBC) Transfusions Week 26 Platelet transfusion	1.0 mean of transfusions number Standard Deviation 1.91

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: Full analysis set, patients who were transfusion dependent

Platelet or RBC transfusions will be based on physician's subjective judgement. Platelet transfusion will be done if the platelet count is less than 10×10\^9/L with significant bleeding tendency or the platelet count is less than 20×10\^9/L with pyrexia. RBC transfusion will be done to keep the hemoglobin concentration at over 7 g/dL or in the presence of clinical symptoms such as dyspnea.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Volume of Platelet and RBC Transfusions Week 26 Platelet transfusion	200.0 mL Standard Deviation 382.97
Volume of Platelet and RBC Transfusions Baseline RBC transfusion	1600.0 mL Standard Deviation 1239.35
Volume of Platelet and RBC Transfusions Week 26 RBC transfusion	400.0 mL Standard Deviation 894.43
Volume of Platelet and RBC Transfusions Baseline Platelet transfusion	687.5 mL Standard Deviation 559.18

SECONDARY outcome

Timeframe: Week 26

The proportions of the subjects for whom the amount of blood transfusion (platelets and RBC) decreased or the proportions of the subjects for whom blood transfusion (platelets and RBC) became unnecessary. Platelet transfusion will be done if the platelet count is less than 10×10\^9/L with significant bleeding tendency or the platelet count is less than 20×10\^9/L with pyrexia. RBC transfusion will be done to keep the hemoglobin concentration at over 7 g/dL or in the presence of clinical symptoms such as dyspnea.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
The Proportion of Subjects Whose Transfusion Unit (or Volume) Are Decreased or Who Became Transfusion (Platelet, RBC) Independent Baseline RBC transfusion dependence	6 Participants
The Proportion of Subjects Whose Transfusion Unit (or Volume) Are Decreased or Who Became Transfusion (Platelet, RBC) Independent RBC Transfusion decrease or free	4 Participants
The Proportion of Subjects Whose Transfusion Unit (or Volume) Are Decreased or Who Became Transfusion (Platelet, RBC) Independent Baseline Platelet transfusion dependence	8 Participants
The Proportion of Subjects Whose Transfusion Unit (or Volume) Are Decreased or Who Became Transfusion (Platelet, RBC) Independent Platelet Transfusion decrease or free	5 Participants

SECONDARY outcome

Timeframe: Week 26

Duration of hospitalization is the time period from the administration of ATG up to discharge.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Duration of Hospitalization	49.0 days Interval 13.0 to 123.0

SECONDARY outcome

Timeframe: Week 26

The time to onset of CR and PR will be determined by measuring platelet, reticulocyte, neutrophil and transfusion independence.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Time to Onset of CR and PR	3.75 months Interval 2.5 to 4.8

SECONDARY outcome

Timeframe: Week 104

Population: Number of participants who responded to treatment (7 out of the 10 participants)

Duration for CR or PR will be determined by measuring platelet, reticulocyte, neutrophil and transfusion independence.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=7 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Duration of CR or PR	17.28 months Interval 6.0 to 20.3

SECONDARY outcome

Timeframe: Week 104

Population: safety population:The safety population consisted of all subjects who received at least one dose of eltrombopag.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Degree of Exposure to Eltrombopag : Average Daily Dose	43.8 mg/day Standard Deviation 23.19

SECONDARY outcome

Timeframe: Week 104

Population: safety population:The safety population consisted of all subjects who received at least one dose of eltrombopag.

The cumulative dose of drug administered to the subject will be calculated.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Degree of Exposure to Eltrombopag : Cumulative Dose	17687.5 mg Standard Deviation 7179.77

SECONDARY outcome

Timeframe: Week 104

Population: safety population:The safety population consisted of all subjects who received at least one dose of eltrombopag.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Degree of Exposure to Eltrombopag : Days on Study	493.7 days Standard Deviation 233.69

SECONDARY outcome

Timeframe: though study completion , approximately 2 years

Population: safety population:The safety population consisted of all subjects who received at least one dose of eltrombopag.

Adverse events will be collected from the start of study treatment until the approval.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Number of Participants With Adverse Events number of participants with an AE	10 Participants
Number of Participants With Adverse Events with an AE related to any study treatment	8 Participants
Number of Participants With Adverse Events with an AE related to Eltrombopag	5 Participants
Number of Participants With Adverse Events with an AE related to CsA	8 Participants
Number of Participants With Adverse Events number of participants with a SAE	2 Participants

SECONDARY outcome

Timeframe: baseline and Week 26

Population: safety set:The safety population consisted of all subjects who received at least one dose of eltrombopag.

Vital sign measurements : blood pressure

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Vital Signs (Blood Pressure) as a Measure of Safety and Tolerability baseline systolic blood pressure (mmHg)	115.7 mmHg Standard Deviation 15.06
Vital Signs (Blood Pressure) as a Measure of Safety and Tolerability week 26 systolic blood pressure (mmHg)	126.4 mmHg Standard Deviation 17.12
Vital Signs (Blood Pressure) as a Measure of Safety and Tolerability baseline diastolic blood pressure (mmHg)	64.3 mmHg Standard Deviation 11.78
Vital Signs (Blood Pressure) as a Measure of Safety and Tolerability week 26 diastolic blood pressure (mmHg)	76.9 mmHg Standard Deviation 13.11

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: safety population: The safety population consisted of all subjects who received at least one dose of eltrombopag.

Triplicate 12-lead ECGs will be obtained at designated time points during the study using an ECG machine that calculates the heart rate and measures PR, QRS, QT, and QT interval corrected by Fridericia formula (QTcF) intervals.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability screening (baseline) · abnormal not clinically significant	2 Participants
12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability screening (baseline) · normal	8 Participants
12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability screening (baseline) · abnormal clinically significant	0 Participants
12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability week 26 · normal	6 Participants
12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability week 26 · abnormal not clinically significant	3 Participants
12-lead Electrocardiogram (ECG) as Measure of Safety and Tolerability week 26 · abnormal clinically significant	0 Participants

SECONDARY outcome

Timeframe: day 15

Population: pharmacokinetic population:The PK population was defined as all subjects whose PK samples were collected and measured.

Blood samples will be collected after repeat (14 days) doses of eltrombopag 75, 50, 25 mg to determine the plasma eltrombopag concentration prior to the next dose.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
The Trough Concentrations of Eltrombopag Following Repeat Doses of at 75 mg, 50 mg and 25 mg Eltrombopag 75 mg day 15, 0h (predose)	21800 ng/mL Standard Deviation 7370
The Trough Concentrations of Eltrombopag Following Repeat Doses of at 75 mg, 50 mg and 25 mg Eltrombopag 25 mg day 15, 0h (predose)	6070 ng/mL Standard Deviation NA only 1 measure (from 1 participant) at that dose level
The Trough Concentrations of Eltrombopag Following Repeat Doses of at 75 mg, 50 mg and 25 mg Eltrombopag 50 mg day 15, 0h (predose)	20800 ng/mL Standard Deviation 7920

SECONDARY outcome

Timeframe: day 15

Population: pharmacokinetic population: The PK population was defined as all subjects whose PK samples were collected and measured.

Blood sample will be collected at 4 hours after repeat (14 days) dose of eltrombopag 75 mg

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
The Concentration After 4 Hours of Dose of Eltrombopag 75 mg day 15, 0 hour (predose)	21800 ng/mL Standard Deviation 7370
The Concentration After 4 Hours of Dose of Eltrombopag 75 mg day 15, 4 hours (post dose)	28400 ng/mL Standard Deviation 8960

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: safety set:The safety population consisted of all subjects who received at least one dose of eltrombopag.

The laboratory test values (haemoglobin and albumin) were calculated at each time point of evaluation.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Composite of Laboratory Parameters Assessment as a Safety Measure (Haemoglobin and Albumin). hemoglobin baseline (g/L)	77.2 g/L Standard Deviation 4.52
Composite of Laboratory Parameters Assessment as a Safety Measure (Haemoglobin and Albumin). hemoglobin week 26 (g/L)	102.4 g/L Standard Deviation 17.64
Composite of Laboratory Parameters Assessment as a Safety Measure (Haemoglobin and Albumin). Albumin baseline (g/L)	38.7 g/L Standard Deviation 4.83
Composite of Laboratory Parameters Assessment as a Safety Measure (Haemoglobin and Albumin). Albumin Week 26 (g/L)	44.9 g/L Standard Deviation 2.52

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: safety set:The safety population consisted of all subjects who received at least one dose of eltrombopag.

The laboratory test values (lymphocytes and neutrophils) were calculated at each time point of evaluation.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils). Total Neutrophils Baseline (Gi/L)	0.4033 Gi/L Standard Deviation 0.38230
Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils). Total Neutrophils Week 26 (Gi/L)	1.6120 Gi/L Standard Deviation 0.468
Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils). White blood cell count baseline (Gi/L)	1.896 Gi/L Standard Deviation 0.9200
Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils). White blood cell count week 26(Gi/L)	2.682 Gi/L Standard Deviation 0.8347
Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils). lymphocytes baseline (Gi/L)	1.3943 Gi/L Standard Deviation 0.60771
Composite of Laboratory Parameters Assessment as a Safety Measure (Lymphocytes and Neutrophils). lymphocytes week 26 (Gi/L)	0.7108 Gi/L Standard Deviation 0.34079

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: safety set:The safety population consisted of all subjects who received at least one dose of eltrombopag.

The laboratory test values (Alcaline Phosphatase and Aspartate Amino Transferase) were calculated at each time point of evaluation.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) . Alcaline phosphatase baseline (IU/L)	186.7 IU/L Standard Deviation 57.03
Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) . Alcaline phosphatase Week 26 (IU/L)	319.6 IU/L Standard Deviation 114.58
Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) . Alanine Amino Transferase baseline (IU/L)	14.3 IU/L Standard Deviation 3.71
Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) . Alanine Amino Transferase Week 26(IU/L)	16.8 IU/L Standard Deviation 7.48
Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) . Aspartate Amino Transferase baseline (IU/L)	14.9 IU/L Standard Deviation 2.47
Composite of Laboratory Parameters Assessment as a Safety Measure (Alcaline Phosphatase and Aspartate Amino Transferase) . Aspartate Amino Transferase Week 26(IU/L)	18.8 IU/L Standard Deviation 4.66

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: safety set:The safety population consisted of all subjects who received at least one dose of eltrombopag.

The laboratory test values (hematological /biochemical examinations) were calculated at each time point of evaluation.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Composite of Laboratory Parameters Assessment as a Safety Measure. Direct Bilirubin baseline (umol/L)	2.565 umol/L Standard Deviation 0.9012
Composite of Laboratory Parameters Assessment as a Safety Measure. Direct Bilirubin week 26 (umol/L)	2.850 umol/L Standard Deviation 1.2092
Composite of Laboratory Parameters Assessment as a Safety Measure. Indirect Bilirubin baseline (umol/L)	5.301 umol/L Standard Deviation 2.2002
Composite of Laboratory Parameters Assessment as a Safety Measure. Indirect Bilirubin week 26 (umol/L)	6.080 umol/L Standard Deviation 1.7336
Composite of Laboratory Parameters Assessment as a Safety Measure. Total Bilirubin baseline (umol/L)	7.866 umol/L Standard Deviation 2.9287
Composite of Laboratory Parameters Assessment as a Safety Measure. Total Bilirubin week 26 (umol/L)	8.930 umol/L Standard Deviation 2.5331
Composite of Laboratory Parameters Assessment as a Safety Measure. Creatinine baseline (umol/L)	59.6700 umol/L Standard Deviation 11.86193
Composite of Laboratory Parameters Assessment as a Safety Measure. Creatinine week 26 (umol/L)	79.9529 umol/L Standard Deviation 23.55122
Composite of Laboratory Parameters Assessment as a Safety Measure. Potassium baseline (umol/L)	3.88 umol/L Standard Deviation 0.371
Composite of Laboratory Parameters Assessment as a Safety Measure. Potassium week 26 (umol/L)	4.27 umol/L Standard Deviation 0.335
Composite of Laboratory Parameters Assessment as a Safety Measure. Sodium baseline (umol/L)	140.7 umol/L Standard Deviation 1.42
Composite of Laboratory Parameters Assessment as a Safety Measure. Sodium week 26 (umol/L)	140.4 umol/L Standard Deviation 1.74

SECONDARY outcome

Timeframe: baseline and Week 26

Population: safety set:The safety population consisted of all subjects who received at least one dose of eltrombopag.

Vital sign measurements : temperature

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Vital Signs (Temperature) as a Measure of Safety and Tolerability baseline temperature (°C)	36.55 °C Standard Deviation 0.448
Vital Signs (Temperature) as a Measure of Safety and Tolerability week 26 temperature (°C)	36.71 °C Standard Deviation 0.379

SECONDARY outcome

Timeframe: baseline and Week 26

Population: safety set:The safety population consisted of all subjects who received at least one dose of eltrombopag.

Vital sign measurements : pulse rate.

Outcome measures

Outcome measures
Measure	Eltrombopag+Rabbit ATG/CsA Arm n=10 Participants Subjects received rabbit ATG diluted by 500 mL of saline or 5% glucose injection at a dose of 2.5 to 3.75 mg per kilogram (kg) per day for 5 days as a slow intravenous infusion over 6 hours. CsA was administered at a dose of 3 mg per kg twice a day from day 0. The dose level was adjusted based on the monitoring of blood level or renal function. Eltrombopag was initiated on day 14 and it could be delayed up to 2 weeks if the subject had infection, serum sickness, or other adverse events. Eltrombopag was administered orally once a day at fasting at an initial dose of 75 mg, and the dose adjusted every 2 weeks according to the platelet count. Eltrombopag and CsA were continued until Week 26. After Week 26, eligible subjects received eltrombopag; and CsA was tapered or maintained as per the investigator's discretion.
Vital Signs (Pulse Rate) as a Measure of Safety and Tolerability baseline heart rate (beats /min)	76.2 beats/min Standard Deviation 10.38
Vital Signs (Pulse Rate) as a Measure of Safety and Tolerability week 26 heart rate (beats/min)	80.4 beats/min Standard Deviation 10.82

Adverse Events

Eltrombopag+ATG/CsA

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Eltrombopag+ATG/CsA n=10 participants at risk Eltrombopag+ATG/CsA
Blood and lymphatic system disorders Febrile neutropenia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Renal and urinary disorders Nephrolithiasis	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description

Other adverse events

Other adverse events
Measure	Eltrombopag+ATG/CsA n=10 participants at risk Eltrombopag+ATG/CsA
Blood and lymphatic system disorders Febrile neutropenia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Eye disorders Dry eye	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Chronic gastritis	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Constipation	40.0% 4/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Dyspepsia	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Gastritis	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Haemorrhoidal haemorrhage	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Lip dry	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Nausea	60.0% 6/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Stomatitis	30.0% 3/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Gastrointestinal disorders Vomiting	40.0% 4/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
General disorders Non-cardiac chest pain	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
General disorders Oedema	40.0% 4/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
General disorders Oedema peripheral	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
General disorders Pyrexia	40.0% 4/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Hepatobiliary disorders Hepatic function abnormal	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Hepatobiliary disorders Liver injury	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Epstein-Barr virus infection	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Genital herpes	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Gingivitis	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Herpes zoster	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Impetigo	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Nasopharyngitis	30.0% 3/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Oral herpes	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Oral infection	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Pneumonia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Infections and infestations Upper respiratory tract infection	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Injury, poisoning and procedural complications Subcutaneous haematoma	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Injury, poisoning and procedural complications Transfusion reaction	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Alanine aminotransferase increased	30.0% 3/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Amylase increased	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Blood alkaline phosphatase increased	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Blood bilirubin increased	30.0% 3/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Blood creatine phosphokinase increased	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Cytomegalovirus test positive	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Electrocardiogram QT prolonged	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Gamma-glutamyltransferase increased	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Lymphocyte count decreased	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Platelet count decreased	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations Serum ferritin increased	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Investigations White blood cell count decreased	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Dyslipidaemia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Electrolyte imbalance	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Hyperglycaemia	30.0% 3/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Hyperkalaemia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Hyperuricaemia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Hypokalaemia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Hypomagnesaemia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Hyponatraemia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Metabolism and nutrition disorders Iron overload	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Musculoskeletal and connective tissue disorders Back pain	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Musculoskeletal and connective tissue disorders Bone pain	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Musculoskeletal and connective tissue disorders Myalgia	30.0% 3/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Musculoskeletal and connective tissue disorders Synovial cyst	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Musculoskeletal and connective tissue disorders Trigger finger	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin papilloma	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Nervous system disorders Dysgeusia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Nervous system disorders Headache	50.0% 5/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Nervous system disorders Paralysis	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Psychiatric disorders Anxiety	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Psychiatric disorders Insomnia	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Renal and urinary disorders Dysuria	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Renal and urinary disorders Haematuria	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Renal and urinary disorders Renal disorder	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Renal and urinary disorders Renal impairment	40.0% 4/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Skin and subcutaneous tissue disorders Acne	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Skin and subcutaneous tissue disorders Blister	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Skin and subcutaneous tissue disorders Erythema	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Skin and subcutaneous tissue disorders Petechiae	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Skin and subcutaneous tissue disorders Pruritus	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Skin and subcutaneous tissue disorders Rash	20.0% 2/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Skin and subcutaneous tissue disorders Sebaceous hyperplasia	10.0% 1/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description
Vascular disorders Hypertension	40.0% 4/10 • Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit up to approximately 2 years. AE additional description

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 1-888-669-6682

Email: [email protected]

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 (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER