Trial Outcomes & Findings for Combination of Eltrombopag With Immunosuppressive Therapy in East-Asian Patients With Severe Aplastic Anemia (NCT NCT04328727)

Last Updated: 2026-01-13

Results Overview

Complete response rate was defined as percentage of patients achieving complete response (CR). Complete response was defined as subjects meeting all the three criteria on two consecutive serial blood count measurements at least one week apart but not more than four weeks apart: * Absolute neutrophil count \> 1.0 ×10\^9/L * Platelet count \> 100 ×10\^9/L * Hemoglobin \> 100 g/L The participants who discontinued from the trial before Week 26 and those that received blood products prior to response assessment (7 days prior for platelet transfusions, 14 days for RBC transfusion and 21 days for growth factors) were treated as non-responders.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Week 26 (6 months after starting study treatment)

Results posted on

2026-01-13

Participant Flow

Participants were enrolled at 12 sites in 4 different countries

there was an up to 30 days screening period (day -30 to -1) before first treatment (day 1).

Participant milestones

Participant milestones
Measure	Eltrombopag Participants received eltrombopag in combination with r-ATG and CsA. * Eltrombopag was administered orally once daily with initial doses of 75mg/day for ≥ 12 years old and 37.5 mg/day for participants between ≥ 6 and \< 12 years. Doses could be adjusted based on platelet count * r-ATG was administered intravenously at a dose of 2.5 to 3.5 mg/kg/day on Days 1-5 * CsA was administered orally every 12 h at a starting dose of 3-6 mg/kg/day
Overall Study STARTED	36
Overall Study Started extension part	28
Overall Study Started long term follow up	34
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Eltrombopag Participants received eltrombopag in combination with r-ATG and CsA. * Eltrombopag was administered orally once daily with initial doses of 75mg/day for ≥ 12 years old and 37.5 mg/day for participants between ≥ 6 and \< 12 years. Doses could be adjusted based on platelet count * r-ATG was administered intravenously at a dose of 2.5 to 3.5 mg/kg/day on Days 1-5 * CsA was administered orally every 12 h at a starting dose of 3-6 mg/kg/day
Overall Study Guardian Decision	1
Overall Study Participant decision	4
Overall Study Death	3

Baseline Characteristics

Combination of Eltrombopag With Immunosuppressive Therapy in East-Asian Patients With Severe Aplastic Anemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eltrombopag n=36 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Age, Categorical <=18 years	8 Participants n=210 Participants
Age, Categorical Between 18 and 65 years	26 Participants n=210 Participants
Age, Categorical >=65 years	2 Participants n=210 Participants
Age, Continuous	34.7 years STANDARD_DEVIATION 18.97 • n=210 Participants
Sex: Female, Male Female	21 Participants n=210 Participants
Sex: Female, Male Male	15 Participants n=210 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=210 Participants
Race (NIH/OMB) Asian	36 Participants n=210 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=210 Participants
Race (NIH/OMB) Black or African American	0 Participants n=210 Participants
Race (NIH/OMB) White	0 Participants n=210 Participants
Race (NIH/OMB) More than one race	0 Participants n=210 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=210 Participants

PRIMARY outcome

Timeframe: Week 26 (6 months after starting study treatment)

Population: The Full Analysis Set (FAS) comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Eltrombopag n=36 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Complete Response (CR) Rate at Week 26 All participants	16.7 percentage of participants Interval 6.4 to 32.8
Complete Response (CR) Rate at Week 26 < 18 years	25 percentage of participants Interval 3.2 to 65.1
Complete Response (CR) Rate at Week 26 18-64 years	15.4 percentage of participants Interval 4.4 to 34.9
Complete Response (CR) Rate at Week 26 ≥ 65 years	0 percentage of participants Interval 0.0 to 84.2

SECONDARY outcome

Timeframe: Week 13 (3 months), Week 52 (12 months) and yearly after up to 3 years

Population: The Full Analysis Set (FAS) comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Eltrombopag n=36 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Complete Response (CR) Rate Week 52	30.6 percentage of participants Interval 16.3 to 48.1
Complete Response (CR) Rate Year 2	30.6 percentage of participants Interval 16.3 to 48.1
Complete Response (CR) Rate Week 13	5.6 percentage of participants Interval 0.7 to 18.7
Complete Response (CR) Rate Year 3	30.6 percentage of participants Interval 16.3 to 48.1

SECONDARY outcome

Timeframe: Week 13 (3 months), 26 weeks (6 months), 52 weeks and yearly after up to 3 years

Population: The Full Analysis Set (FAS) comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

Overall response rate was defined as percentage of patients achieving complete response (CR) or partial response (PR). Partial response (PR) was defined as blood counts no longer meeting the standard criteria for severe pancytopenia in SAA, equivalent to at least 2 of the 3 criteria below, but not sufficient for a CR: * Absolute neutrophil count ≥ 0.5 × 10\^9/L * Platelet count ≥ 20 × 10\^9/L * Reticulocyte count ≥ 20 × 10\^9/L Complete response (CR) was defined as subjects meeting all the three criteria on two consecutive serial blood count measurements at least one week apart but not more than four weeks apart: * Absolute neutrophil count \> 1.0 ×10\^9/L * Platelet count \> 100 ×10\^9/L * Hemoglobin \> 100 g/L

Outcome measures

Outcome measures
Measure	Eltrombopag n=36 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Overall Response (ORR) Rate Week 13	66.7 percentage of participants Interval 49.0 to 81.4
Overall Response (ORR) Rate Week 26	77.8 percentage of participants Interval 60.8 to 89.9
Overall Response (ORR) Rate Week 52	66.7 percentage of participants Interval 49.0 to 81.4
Overall Response (ORR) Rate Year 2	50.0 percentage of participants Interval 32.9 to 67.1
Overall Response (ORR) Rate Year 3	41.7 percentage of participants Interval 25.5 to 59.2

SECONDARY outcome

Timeframe: Up to aproximately 3 years

Population: Participants in the Full Analysis Set (FAS) who achieved complete response. FAS comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

Duration of response was derived as the time from first documented and confirmed complete response (CR) until the time of relapse or death, whichever occurred first. Duration of response was estimated using Kaplan-Meier method. Clinical relapse was considered as the occurrence of any of the following events in a participant who had achieved a hematological response (CR) but had subsequently lost response (not explained by any other independent concomitant medical conditions) in one blood count measurements: * Meeting again the criteria for SAA * Requirement for transfusion again for subjects who had been transfusion independent * Decrease in any of the peripheral blood counts to absolute neutrophil count \< 0.5 x10\^9/L or platelets \< 20 x10\^9/L.

Outcome measures

Outcome measures
Measure	Eltrombopag n=11 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Duration of Complete Response	NA months NA: Not estimable due to insufficient number of participants with relapse or death (all participants with CR at Week 52 were still responding without any documented relapse at Year 3)

SECONDARY outcome

Timeframe: Up to aproximately 3 years

Population: Participants in the Full Analysis Set (FAS) who achieved a response. FAS comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

Duration of response was derived as the time from first documented and confirmed response (either CR or PR) until the time of relapse or death, whichever occurred first. Duration of response was estimated using Kaplan-Meier method. Clinical relapse was considered as the occurrence of any of the following events in a participant who had achieved a hematological response (CR or PR) but had subsequently lost response (not explained by any other independent concomitant medical conditions) in one blood count measurements: * Meeting again the criteria for SAA * Requirement for transfusion again for subjects who had been transfusion independent * Decrease in any of the peripheral blood counts to absolute neutrophil count \< 0.5 x10\^9/L or platelets \< 20 x10\^9/L.

Outcome measures

Outcome measures
Measure	Eltrombopag n=31 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Duration of Overall Response	NA months Interval 3.1 to NA: Not estimable due to median duration of overall response not being achieved from the analysis due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to approximately 3 years

Population: The Full Analysis Set (FAS) comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. If a subject was not known to have died, survival was censored at the date of last contact. The distribution function of OS was estimated using the Kaplan- Meier method.

Outcome measures

Outcome measures
Measure	Eltrombopag n=36 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Overall Survival (OS)	NA Months NA: Not estimable due to median duration of overall survival being not evaluable from the Kaplan-Meyer analysis due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Week 26, Week 52 and yearly after up to 3 years

Population: The Full Analysis Set (FAS) comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

OS was defined as the time from the date of the first dose of study treatment to the date of death due to any cause. The OS rate is the estimated probability that a patient will remain event-free up to the specified time point and was obtained from the Kaplan-Meier survival estimates. If a subject was not known to have died, survival was censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Eltrombopag n=36 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Overall Survival (OS) Rate Week 26	97.2 percent probability Interval 81.9 to 99.6
Overall Survival (OS) Rate Week 52	97.2 percent probability Interval 81.9 to 99.6
Overall Survival (OS) Rate Year 2	94.1 percent probability Interval 78.3 to 95.5
Overall Survival (OS) Rate Year 3	90.9 percent probability Interval 74.4 to 97.0

SECONDARY outcome

Timeframe: Week 13, 26

Population: The Full Analysis Set (FAS) subjects with response assessment at week 13 and 26. FAS comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

Transfusion-free interval was defined as the time from most recent RBC/platelet transfusion preceding response assessment to the date of response assessment.

Outcome measures

Outcome measures
Measure	Eltrombopag n=34 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Red Blood Cells (RBC) and Platelet Transfusion-free Interval Before Week 13 and 26 Platelet transfusion-free interval - Week 26	97.3 days Standard Deviation 58.93
Red Blood Cells (RBC) and Platelet Transfusion-free Interval Before Week 13 and 26 RBC transfusion-free interval - Week 13	36.3 days Standard Deviation 25.62
Red Blood Cells (RBC) and Platelet Transfusion-free Interval Before Week 13 and 26 RBC transfusion-free interval - Week 26	98.9 days Standard Deviation 57.97
Red Blood Cells (RBC) and Platelet Transfusion-free Interval Before Week 13 and 26 Platelet transfusion-free interval - Week 13	34.0 days Standard Deviation 25.64

SECONDARY outcome

Timeframe: From date of first dose to approximately 3 years

Population: Full Analysis Set (FAS) subjects who were transfusion dependent at baseline. FAS comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

Transfusion independent participants were defined as those participants who were transfusion dependent at baseline but became transfusion free for a period of ≥ 8 weeks post-baseline for RBCs.

Outcome measures

Outcome measures
Measure	Eltrombopag n=29 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Percentage of Participants Who Become RBC Transfusion Independent	86.2 percentage of participants

SECONDARY outcome

Timeframe: From date of first dose to approximately 3 years

Population: The Full Analysis Set (FAS) subjects who were transfusion dependent at baseline. FAS comprised of all participants to whom study treatment has been assigned and who received at least one dose of study treatment.

Transfusion independent participants were defined as those participants who were transfusion dependent at baseline but became transfusion free for a period of ≥ 4 weeks post-baseline for platelets.

Outcome measures

Outcome measures
Measure	Eltrombopag n=34 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Percentage of Participants Who Become Platelet Transfusion Independent	88.2 percentage of participants

SECONDARY outcome

Timeframe: From date of first dose to approximately 3 years

Population: Participants who received at least one dose of study treatment and presented a clonal evolution event.

Clonal evolution events were assessed by karyotyping (G-banding) and FISH (Fluorescence in situ hybridization) targeting abnormalities including, but not restricted to chromosome 3q del,5q del, monosomy 7, trisomy 8 and those associated with SAA (Severe aplastic anemia), MDS (Myelodysplastic syndrome), AML (Acute myeloid leukemia). Time to clonal evolution was to be estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Eltrombopag n=2 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Time From the Date of First Dose of Investigational Treatment to the Date of First Occurrence of Any Clonal Evolution Events	NA weeks NA: Not estimable due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Pre-dose, and 2, 4, 6, 8 and 24 hours post-dose on Day 14 after initial dose

Population: Participants in the PAS with a an available value for the outcome measure. The Pharmacokinetic analysis set (PAS) includes all participants who received at least one dose of eltrombopag and provide at least one evaluable PK sample.

AUClast is the area under the curve from time zero to the last measurable concentration sampling time. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS) approach.

Outcome measures

Outcome measures
Measure	Eltrombopag n=14 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Plasma Pharmacokinetics (PK) Parameters of Eltrombopag: AUClast	602000 ng*h/mL Standard Deviation 239000

SECONDARY outcome

Timeframe: Pre-dose, and 2, 4, 6, 8 and 24 hours post-dose on Day 14 after initial dose

AUCtau is area under the curve calculated to the end of a dosing interval (tau) at steady-state Blood samples were collected from patients to assess the plasma concentrations of eltrombopag using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS) approach.

Outcome measures

Outcome measures
Measure	Eltrombopag n=12 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Plasma Pharmacokinetics (PK) Parameters of Eltrombopag: AUCtau	585000 ng*h/mL Standard Deviation 231000

SECONDARY outcome

Timeframe: Pre-dose on day 15 after initation of eltrombopag and and pre-dose on the 15th day after each new dose up to week 26

Cthrough is the pre-dose concentration at the end of dose interval. Blood samples were collected to assess the plasma concentrations of eltrombopag using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS) approach. Eltrombopag was administered orally once daily with initial doses of 75mg/day for ≥ 12 years old and 37.5 mg/day for participants between ≥ 6 and \< 12 years. Doses could be adjusted based on platelet count every 2 weeks by decreasing it by 25 mg/day (12.5 mg/day, for participants below 12 years old) if the platelet count was above 200×10\^9/L. or interrupted if platelet count rose above 400×10\^9/L. In partial response participants dose could be restarted or increased to that before the decrease if platelet counts \< 30 x10\^9/L, Hb\< 90 g/L, ANC\< 0.5 x 10\^9/L or participant needed transfusion. In complete response participants dose could be restarted or increased to that before decrease if blood counts dropped to not meet CR criteria.

Outcome measures

Outcome measures
Measure	Eltrombopag n=36 measurements Participants received eltrombopag in combination with r-ATG and CsA.
Plasma Pharmacokinetics (PK) Parameters of Eltrombopag: Ctrough	20200 ng/mL Standard Deviation 9410

SECONDARY outcome

Timeframe: Pre-dose, and 2, 4, 6, 8 and 24 hours post-dose on Day 14 after initial dose

Cmax is the The maximum (peak) observed plasma drug concentration after dose administration. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS) approach.

Outcome measures

Outcome measures
Measure	Eltrombopag n=14 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Plasma Pharmacokinetics (PK) Parameters of Eltrombopag: Cmax	32500 ng/mL Standard Deviation 12300

SECONDARY outcome

Timeframe: Pre-dose, and 2, 4, 6, 8 and 24 hours post-dose on Day 14 after initial dose

Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS) approach.

Outcome measures

Outcome measures
Measure	Eltrombopag n=14 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Plasma Pharmacokinetics (PK) Parameters of Eltrombopag: Tmax	5.59 hours Standard Deviation 5.64

SECONDARY outcome

Timeframe: Pre-dose, and 2, 4, 6, 8 and 24 hours post-dose on Day 14 after initial dose

CLss/F is Apparent systemic (or total body) clearance at steady state from plasma. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag using a validated liquid chromatography - tandem mass spectrometry assay (LC-MS/MS) approach.

Outcome measures

Outcome measures
Measure	Eltrombopag n=12 Participants Participants received eltrombopag in combination with r-ATG and CsA.
Plasma Pharmacokinetics (PK) Parameters of Eltrombopag: CLss/F	0.148 Liter/hour Standard Deviation 0.0618

Adverse Events

Eltrombopag

Serious events: 14 serious events

Other events: 36 other events

Deaths: 1 deaths

Eltrombopag (Post-treatment Long Term Follow-up)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

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

Restriction type: OTHER

Measure	Eltrombopag n=36 participants at risk Participants received eltrombopag in combination with r-ATG and CsA.	Eltrombopag (Post-treatment Long Term Follow-up) Deaths collected in the post- treatment long term follow-up period (starting from day 31 after last dose). No AEs were collected during this period
Hepatobiliary disorders Drug-induced liver injury	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Hepatobiliary disorders Hepatic function abnormal	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Infections and infestations Herpes zoster	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Infections and infestations Sepsis	8.3% 3/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Infections and infestations Urinary tract infection	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Investigations Alanine aminotransferase increased	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Investigations Aspartate aminotransferase increased	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Investigations Blood bilirubin increased	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Investigations Gamma-glutamyltransferase increased	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Investigations Neutrophil count decreased	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Metabolism and nutrition disorders Hyperuricaemia	11.1% 4/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Metabolism and nutrition disorders Hypokalaemia	5.6% 2/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Metabolism and nutrition disorders Hyponatraemia	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Renal and urinary disorders Hydronephrosis	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Reproductive system and breast disorders Breast hyperplasia	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up
Reproductive system and breast disorders Heavy menstrual bleeding	2.8% 1/36 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up	— 0/0 • All-cause mortality: from first dose of study treatment up to 2 years after last dose including post-treatment long term follow up period up to 3.1 years approximately. Serious and Other Adverse Events: from first dose of study treatment until 30 days after last dose up to 1.1 years approximately. No adverse events where collected during the long term follow up