Trial Outcomes & Findings for Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529 (NCT NCT01342952)

NCT ID: NCT01342952

Last Updated: 2022-12-30

Results Overview

AE was defined as any untoward medical occurrence in participant or clinical investigation participant,temporally associated with use of medicinal product, whether or not considered related to medicinal product.SAE was defined as any untoward medical occurrence that, at any dose: results in death,is life threatening, requires hospitalization or prolongation of existing hospitalization,results in disability or incapacity,or is congenital anomaly or birth defect, important medical events that may not immediately life threatening or result in death or hospitalization but may jeopardize participant or may require medical or surgical intervention as per medical or scientific judgement or associated with drug-induced liver injury.TEAE is any event that was not present prior to initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs which were not serious TEAEs were considered as non serious TEAEs.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 38 participants
• Primary outcome timeframe: Up to 10 years and 11 months
• Results posted on: 2022-12-30

Participant Flow

This was an open label, long term extension of study AMB112529 (NCT01342952) which evaluated safety and tolerability of ambrisentan in the pediatric (aged 8 years up to 18 years) Pulmonary Arterial Hypertension (PAH) population.

A total of 38 participants were enrolled in this study.

Participant milestones

Measure	Ambrisentan 2.5 mg (ITT) Participants received ambrisentan 2.5 milligrams (mg) dose of ambrisentan orally in tablet/s form once daily. The Intent-to-Treat (ITT) Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 5 mg (ITT) Participants received 5 mg dose of ambrisenten orally in tablet form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 7.5 mg (ITT) Participants received 7.5 mg dose of ambrisentan orally in tablet/s form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 10 mg (ITT) Participants received 10 mg dose of ambrisentan orally in tablet/s form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.
Overall Study STARTED	9	19	5	5
Overall Study Intent-to-Treat Population	9	19	5	5
Overall Study Safety Population	4	16	6	12
Overall Study COMPLETED	5	8	3	5
Overall Study NOT COMPLETED	4	11	2	0

Reasons for withdrawal

Measure	Ambrisentan 2.5 mg (ITT) Participants received ambrisentan 2.5 milligrams (mg) dose of ambrisentan orally in tablet/s form once daily. The Intent-to-Treat (ITT) Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 5 mg (ITT) Participants received 5 mg dose of ambrisenten orally in tablet form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 7.5 mg (ITT) Participants received 7.5 mg dose of ambrisentan orally in tablet/s form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 10 mg (ITT) Participants received 10 mg dose of ambrisentan orally in tablet/s form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.
Overall Study Adverse Event	0	5	1	0
Overall Study Lost to Follow-up	0	2	0	0
Overall Study Withdrawal by Subject	1	1	0	0
Overall Study Physician Decision	3	3	1	0

Baseline Characteristics

Long-term Ambrisentan Extension Study for Pediatric Patients Who Participated in AMB112529

Baseline characteristics by cohort

Measure	Ambrisentan 2.5 mg (ITT) n=9 Participants Participants received ambrisentan 2.5 milligrams (mg) dose of ambrisentan orally in tablet/s form once daily. The Intent-to-Treat (ITT) Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 5 mg (ITT) n=19 Participants Participants received 5 mg dose of ambrisenten orally in tablet form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 7.5 mg (ITT) n=5 Participants Participants received 7.5 mg dose of ambrisentan orally in tablet/s form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Ambrisentan 10 mg (ITT) n=5 Participants Participants received 10 mg dose of ambrisentan orally in tablet/s form once daily. The ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to ITT treatment group at the start of study AMB114588.	Total n=38 Participants Total of all reporting groups
Age, Continuous	9.7 Years STANDARD_DEVIATION 2.29 • n=5 Participants	11.9 Years STANDARD_DEVIATION 2.57 • n=7 Participants	12.6 Years STANDARD_DEVIATION 2.61 • n=5 Participants	15.2 Years STANDARD_DEVIATION 0.84 • n=4 Participants	11.9 Years STANDARD_DEVIATION 2.81 • n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	9 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	25 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	10 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	13 Participants n=21 Participants
Race/Ethnicity, Customized African American/African Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	4 Participants n=5 Participants	14 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	27 Participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 10 years and 11 months

Population: Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588)

AE was defined as any untoward medical occurrence in participant or clinical investigation participant,temporally associated with use of medicinal product, whether or not considered related to medicinal product.SAE was defined as any untoward medical occurrence that, at any dose: results in death,is life threatening, requires hospitalization or prolongation of existing hospitalization,results in disability or incapacity,or is congenital anomaly or birth defect, important medical events that may not immediately life threatening or result in death or hospitalization but may jeopardize participant or may require medical or surgical intervention as per medical or scientific judgement or associated with drug-induced liver injury.TEAE is any event that was not present prior to initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. TEAEs which were not serious TEAEs were considered as non serious TEAEs.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=16 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=6 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=12 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) Non-STEAEs	3 Participants	13 Participants	5 Participants	10 Participants
Number of Participants With Non-serious Treatment-emergent Adverse Events (Non-STEAEs) and Serious Treatment-emergent Adverse Events (STEAEs) STEAEs	2 Participants	7 Participants	4 Participants	8 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALT, AST, GGT, total bilirubin. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin ALT	-7.5 Millimoles per liter Standard Deviation 12.56	-1.0 Millimoles per liter Standard Deviation 8.64	0.8 Millimoles per liter Standard Deviation 4.09	4.0 Millimoles per liter Standard Deviation 7.42
Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin AST	-11.8 Millimoles per liter Standard Deviation 6.29	-5.6 Millimoles per liter Standard Deviation 7.23	-1.0 Millimoles per liter Standard Deviation 2.55	-2.1 Millimoles per liter Standard Deviation 8.13
Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin GGT	-0.5 Millimoles per liter Standard Deviation 15.00	-7.0 Millimoles per liter Standard Deviation 10.45	-0.8 Millimoles per liter Standard Deviation 8.44	-4.6 Millimoles per liter Standard Deviation 28.30
Change From Baseline in Liver Function Parameters: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Total Bilirubin Total bilirubin	-5.3 Millimoles per liter Standard Deviation 12.47	-4.0 Millimoles per liter Standard Deviation 3.30	-2.8 Millimoles per liter Standard Deviation 6.06	3.1 Millimoles per liter Standard Deviation 8.45

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following clinical chemistry parameters: Calcium, chloride, CO2 content, glucose, potassium, magnesium, sodium, phosphorus inorganic, and BUN. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) Calcium	-0.150 Millimoles per liter Standard Deviation 0.1769	-0.054 Millimoles per liter Standard Deviation 0.0779	0.028 Millimoles per liter Standard Deviation 0.0630	-0.060 Millimoles per liter Standard Deviation 0.1075
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) Chloride	1.7 Millimoles per liter Standard Deviation 5.13	2.6 Millimoles per liter Standard Deviation 1.65	0.4 Millimoles per liter Standard Deviation 3.44	-0.6 Millimoles per liter Standard Deviation 2.96
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) CO2 content	-0.3 Millimoles per liter Standard Deviation 2.89	2.2 Millimoles per liter Standard Deviation 1.87	0.2 Millimoles per liter Standard Deviation 3.70	0.0 Millimoles per liter Standard Deviation 1.80
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) Glucose	0.167 Millimoles per liter Standard Deviation 0.4163	-0.150 Millimoles per liter Standard Deviation 1.1414	0.120 Millimoles per liter Standard Deviation 0.5541	0.478 Millimoles per liter Standard Deviation 0.9107
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) Potassium	-0.30 Millimoles per liter Standard Deviation 0.529	-0.07 Millimoles per liter Standard Deviation 0.337	-0.02 Millimoles per liter Standard Deviation 0.148	-0.12 Millimoles per liter Standard Deviation 0.327
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) Magnesium	-0.100 Millimoles per liter Standard Deviation 0.0872	-0.062 Millimoles per liter Standard Deviation 0.0898	0.028 Millimoles per liter Standard Deviation 0.0683	0.012 Millimoles per liter Standard Deviation 0.0716
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) Sodium	2.7 Millimoles per liter Standard Deviation 1.15	1.0 Millimoles per liter Standard Deviation 1.63	-0.2 Millimoles per liter Standard Deviation 0.84	0.7 Millimoles per liter Standard Deviation 1.87
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) Phosphorus inorganic	-0.340 Millimoles per liter Standard Deviation 0.1311	-0.159 Millimoles per liter Standard Deviation 0.3055	-0.212 Millimoles per liter Standard Deviation 0.3440	-0.108 Millimoles per liter Standard Deviation 0.2408
Change From Baseline in Chemistry Parameters: Calcium, Chloride, Carbon Dioxide (CO2) Content, Glucose, Potassium, Magnesium, Sodium, Phosphorus Inorganic, Blood Urea Nitrogen (BUN) BUN	-0.10 Millimoles per liter Standard Deviation 1.808	-0.51 Millimoles per liter Standard Deviation 1.649	-0.14 Millimoles per liter Standard Deviation 1.274	0.33 Millimoles per liter Standard Deviation 1.507

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALP, CK, LDH. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) ALP	-77.7 International units per Liter Standard Deviation 57.01	-109.5 International units per Liter Standard Deviation 71.51	-148.8 International units per Liter Standard Deviation 151.78	-135.6 International units per Liter Standard Deviation 97.33
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) CK	-18.7 International units per Liter Standard Deviation 23.07	4.0 International units per Liter Standard Deviation 100.83	46.6 International units per Liter Standard Deviation 89.55	-9.7 International units per Liter Standard Deviation 13.96
Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Creatine Kinase (CK), Lactate Dehydrogenase (LDH) LDH	-40.3 International units per Liter Standard Deviation 45.54	-48.9 International units per Liter Standard Deviation 71.64	-12.8 International units per Liter Standard Deviation 22.58	-28.3 International units per Liter Standard Deviation 37.23

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following clinical chemistry parameters: Creatinine, uric acid. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid Creatinine	6.27 Micromoles per liter Standard Deviation 19.775	8.16 Micromoles per liter Standard Deviation 9.602	10.26 Micromoles per liter Standard Deviation 8.008	19.31 Micromoles per liter Standard Deviation 14.698
Change From Baseline in Chemistry Parameters: Creatinine, Uric Acid Uric acid	-64.67 Micromoles per liter Standard Deviation 119.169	-83.60 Micromoles per liter Standard Deviation 90.103	-45.40 Micromoles per liter Standard Deviation 77.584	21.22 Micromoles per liter Standard Deviation 79.330

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following clinical chemistry parameters: Albumin, total protein. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Chemistry Parameters: Albumin, Total Protein Albumin	-3.3 Grams per liter Standard Deviation 4.04	-1.2 Grams per liter Standard Deviation 3.16	1.6 Grams per liter Standard Deviation 1.14	-2.0 Grams per liter Standard Deviation 4.42
Change From Baseline in Chemistry Parameters: Albumin, Total Protein Total protein	-3.7 Grams per liter Standard Deviation 4.51	-3.4 Grams per liter Standard Deviation 4.93	3.0 Grams per liter Standard Deviation 5.24	-3.0 Grams per liter Standard Deviation 7.33

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following hematology parameters: Hemoglobin and MCHC. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=9 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) Hemoglobin	-23.0 Grams per Liter Standard Deviation 38.63	-4.7 Grams per Liter Standard Deviation 16.15	0.8 Grams per Liter Standard Deviation 9.71	1.3 Grams per Liter Standard Deviation 20.12
Change From Baseline in Hematology Parameters: Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) MCHC	-9.3 Grams per Liter Standard Deviation 16.01	-12.4 Grams per Liter Standard Deviation 17.31	-6.0 Grams per Liter Standard Deviation 12.98	-1.1 Grams per Liter Standard Deviation 11.72

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following hematology parameters: Hematocrit. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=9 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Hematology Parameters: Hematocrit	-0.0610 Proportion of red blood cells in blood Standard Deviation 0.10235	-0.0004 Proportion of red blood cells in blood Standard Deviation 0.04543	0.0100 Proportion of red blood cells in blood Standard Deviation 0.02884	0.0040 Proportion of red blood cells in blood Standard Deviation 0.06572

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following hematology parameters: Basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC, platelet count. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=9 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count Basophils	-0.007 Giga cells per Liter Standard Deviation 0.0153	0.019 Giga cells per Liter Standard Deviation 0.0417	-0.006 Giga cells per Liter Standard Deviation 0.0152	-0.002 Giga cells per Liter Standard Deviation 0.0148
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count Eosinophils	-0.210 Giga cells per Liter Standard Deviation 0.4139	0.034 Giga cells per Liter Standard Deviation 0.1096	-0.026 Giga cells per Liter Standard Deviation 0.0602	0.009 Giga cells per Liter Standard Deviation 0.0746
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count Lymphocytes	-1.107 Giga cells per Liter Standard Deviation 0.7310	-0.329 Giga cells per Liter Standard Deviation 1.1373	-0.152 Giga cells per Liter Standard Deviation 0.6937	-0.394 Giga cells per Liter Standard Deviation 1.1063
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count Monocytes	-0.013 Giga cells per Liter Standard Deviation 0.1550	0.040 Giga cells per Liter Standard Deviation 0.1273	-0.006 Giga cells per Liter Standard Deviation 0.1635	0.037 Giga cells per Liter Standard Deviation 0.1986
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count Total neutrophils	0.677 Giga cells per Liter Standard Deviation 1.9014	-0.974 Giga cells per Liter Standard Deviation 1.2239	0.412 Giga cells per Liter Standard Deviation 0.6278	0.524 Giga cells per Liter Standard Deviation 2.0030
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count WBC	-0.67 Giga cells per Liter Standard Deviation 2.616	-1.22 Giga cells per Liter Standard Deviation 2.072	0.22 Giga cells per Liter Standard Deviation 0.421	0.18 Giga cells per Liter Standard Deviation 2.787
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC), Platelet Count Platelet count	-34.0 Giga cells per Liter Standard Deviation 27.18	-29.3 Giga cells per Liter Standard Deviation 50.03	-9.2 Giga cells per Liter Standard Deviation 30.87	-0.4 Giga cells per Liter Standard Deviation 64.78

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following hematology parameter: Mean Corpuscle Hemoglobin. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=9 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Hematology Parameter: Mean Corpuscle Hemoglobin	-1.70 Picograms Standard Deviation 3.315	-1.46 Picograms Standard Deviation 2.823	-0.70 Picograms Standard Deviation 1.512	0.11 Picograms Standard Deviation 1.981

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following hematology parameter: Mean Corpuscle Volume. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=9 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Hematology Parameter: Mean Corpuscle Volume	-2.3 Femtoliters Standard Deviation 6.66	-1.0 Femtoliters Standard Deviation 5.52	-0.8 Femtoliters Standard Deviation 2.68	0.8 Femtoliters Standard Deviation 5.61

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected from participants for analysis of following hematology parameters: Red Blood Cell count, reticulocytes. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=9 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=9 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes Red Blood Cell count	-0.57 Trillion cells per liter Standard Deviation 0.862	0.07 Trillion cells per liter Standard Deviation 0.387	0.14 Trillion cells per liter Standard Deviation 0.251	0.00 Trillion cells per liter Standard Deviation 0.497
Change From Baseline in Hematology Parameters: Red Blood Cell Count, Reticulocytes Reticulocytes	0.01427 Trillion cells per liter Standard Deviation 0.024625	-0.00816 Trillion cells per liter Standard Deviation 0.043615	0.00906 Trillion cells per liter Standard Deviation 0.013265	0.01843 Trillion cells per liter Standard Deviation 0.041832

PRIMARY outcome

Timeframe: Up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Physical examination included measurement of liver size. Any abnormal enlargement or reduction in the size of the liver is reported. Liver size was assessed as normal or abnormal. Data for abnormal (improved, worsened and unchanged) liver size is presented. End of study visit data is presented.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size Liver Size: Abnormal: Improved	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size Liver Size: Abnormal: Worsened	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Values for Physical Examination Parameter: Liver Size Liver Size: Abnormal: Unchanged	0 Participants	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Physical examination included measurement of Jugular venous pressure. Jugular venous pressure was assessed as normal or abnormal. Data for abnormal (improved, worsened and unchanged) jugular venous pressure is presented. End of study visit data is presented.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure Jugular Venous Pressure: Abnormal: Improved	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure Jugular Venous Pressure: Abnormal: Worsened	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Values for Physical Examination Parameter: Jugular Venous Pressure Jugular Venous Pressure: Abnormal: Unchanged	0 Participants	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Physical examination included measurement of ascites. Ascites were assessed as present or absent. Data for ascites present with improved, worsened and unchanged is presented. End of study visit data is presented.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites Ascites: Present: Improved	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites Ascites: Present: Worsened	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Values for Physical Examination Parameters: Ascites Ascites: Present: Unchanged	0 Participants	0 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Physical examination included measurement of peripheral edema. Peripheral edema were assessed as present or absent. Data for peripheral edema present with improved, worsened and unchanged is presented. End of study visit data is presented.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema Peripheral edema: Present: Improved	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema Peripheral edema: Present: Worsened	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Values for Physical Examination Parameter: Peripheral Edema Peripheral edema: Present: Unchanged	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Physical examination included measurement of saturated oxygen. End of study visit data is presented.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Percentage of Saturated Oxygen Level (Physical Examination Parameter)	95.5 Percentage of oxygen saturation Standard Deviation 4.20	96.8 Percentage of oxygen saturation Standard Deviation 2.04	97.4 Percentage of oxygen saturation Standard Deviation 1.34	96.9 Percentage of oxygen saturation Standard Deviation 1.97

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

SBP and DBP was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP	16.3 Millimeters of mercury Standard Deviation 16.38	8.4 Millimeters of mercury Standard Deviation 17.99	1.2 Millimeters of mercury Standard Deviation 18.63	8.5 Millimeters of mercury Standard Deviation 12.22
Change From Baseline in Vital Signs Parameter: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP	1.5 Millimeters of mercury Standard Deviation 5.80	2.3 Millimeters of mercury Standard Deviation 12.70	3.6 Millimeters of mercury Standard Deviation 16.96	2.1 Millimeters of mercury Standard Deviation 9.67

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Heart rate was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Vital Signs Parameter: Heart Rate	-9.0 Beats per minute Standard Deviation 13.44	-4.0 Beats per minute Standard Deviation 8.08	-3.8 Beats per minute Standard Deviation 11.50	-6.0 Beats per minute Standard Deviation 15.06

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Weight was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Vital Signs Parameter: Weight	17.43 Kilograms Standard Deviation 12.695	10.73 Kilograms Standard Deviation 8.628	7.12 Kilograms Standard Deviation 5.346	12.17 Kilograms Standard Deviation 16.300

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Height was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Vital Sign Parameter: Height	25.3 Centimeters Standard Deviation 19.99	9.9 Centimeters Standard Deviation 9.92	7.2 Centimeters Standard Deviation 9.47	12.1 Centimeters Standard Deviation 17.55

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Body mass index was measured for the participants at indicated time points. Body mass index was calculated as weight in kilograms (kg) divided by the square of their height in meters (m^2). Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Vital Sign Parameter: Body Mass Index	2.65 Kilogram per meter square Standard Deviation 2.195	2.45 Kilogram per meter square Standard Deviation 1.828	1.52 Kilogram per meter square Standard Deviation 1.633	1.99 Kilogram per meter square Standard Deviation 2.642

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Body surface area was measured for the participants at indicated time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=10 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=5 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=10 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Vital Sign Parameter: Body Surface Area	0.398 Meter square Standard Deviation 0.3024	0.207 Meter square Standard Deviation 0.1744	0.144 Meter square Standard Deviation 0.1254	0.236 Meter square Standard Deviation 0.3163

PRIMARY outcome

Timeframe: Up to 10 years and 11 months

Population: Safety Population.

12-lead ECG was measured in a semi-supine position using an automated ECG machine. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Data for any time till end of study were presented.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=16 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=6 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=12 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal, not clinically significant	4 Participants	14 Participants	3 Participants	9 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Abnormal, clinically significant	0 Participants	2 Participants	1 Participants	3 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=6 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=3 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=7 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study FSH	0.200 International units per Liter Standard Deviation 1.2490	3.217 International units per Liter Standard Deviation 4.0455	0.100 International units per Liter Standard Deviation 3.6042	-0.336 International units per Liter Standard Deviation 3.7053
Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at End of Study LH	0.03 International units per Liter Standard Deviation 0.058	5.17 International units per Liter Standard Deviation 9.665	4.17 International units per Liter Standard Deviation 9.563	0.61 International units per Liter Standard Deviation 9.778

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=3 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=1 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=3 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants FSH	35.800 International units per Liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	0.800 International units per Liter Standard Deviation 1.2530	-2.500 International units per Liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	0.967 International units per Liter Standard Deviation 0.3055
Change From Baseline in Plasma Endocrine Parameters - Female: Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) at 20 Years of Age of Participants LH	8.60 International units per Liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	6.17 International units per Liter Standard Deviation 16.717	-6.30 International units per Liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	5.10 International units per Liter Standard Deviation 4.597

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. At end of study, participants did not receive Ambrisentan 7.5 mg dose for evaluation of Inhibin B hence N=0

Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=2 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=5 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=4 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at End of Study	0.0 Nanogram per liter Standard Deviation 11.31	14.0 Nanogram per liter Standard Deviation 67.48	—	-29.0 Nanogram per liter Standard Deviation 27.60

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=2 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=1 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Inhibin B at 20 Years of Age of Participants	0.0 Nanogram per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	49.0 Nanogram per liter Standard Deviation 110.31	37.0 Nanogram per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	7.5 Nanogram per liter Standard Deviation 70.00

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=2 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=6 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=4 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at End of Study	-10.0 Nanomoles per liter Standard Deviation 1.41	11.8 Nanomoles per liter Standard Deviation 14.22	0.5 Nanomoles per liter Standard Deviation 0.71	17.3 Nanomoles per liter Standard Deviation 22.31

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=3 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=1 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Sex Hormone Binding Globulin at 20 Years of Age of Participants	49.0 Nanomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	1.7 Nanomoles per liter Standard Deviation 54.37	10.0 Nanomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	-15.5 Nanomoles per liter Standard Deviation 2.12

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Estrone level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=5 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=5 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at End of Study	0.00 Picomole per milliliter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	-6.80 Picomole per milliliter Standard Deviation 178.361	-26.00 Picomole per milliliter Standard Deviation 209.304	17.00 Picomole per milliliter Standard Deviation 125.913

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Estrone level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=2 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=1 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Estrone at 20 Years of Age of Participants	-7.00 Picomole per milliliter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	179.00 Picomole per milliliter Standard Deviation 196.576	11.00 Picomole per milliliter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	89.00 Picomole per milliliter Standard Deviation 73.539

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Estriol level of female participants will be measured. Only those parameters having status as overall will be presented. Baseline is the last value recorded prior to start of study treatment from AMB112529. Change from Baseline is calculated by subtracting the Baseline value from the end of study post-dose visit value. Data for this endpoint will be available for this endpoint by June 2023

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Estriol level of female participants will be measured. Only those parameters having status as overall will be presented. Baseline is the last value recorded prior to start of study treatment from AMB112529.Change from Baseline is calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants. Data for this endpoint will be available for this endpoint by June 2023

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Estradiol level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=4 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=5 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at End of Study	-11.00 Picomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	-77.25 Picomoles per liter Standard Deviation 211.435	-255.50 Picomoles per liter Standard Deviation 427.800	44.80 Picomoles per liter Standard Deviation 264.452

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Estradiol level of female participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=1 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=1 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Female: Estradiol at 20 Years of Age of Participants	55.50 Picomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	-107.00 Picomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	15.00 Picomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	387.50 Picomoles per liter Standard Deviation 375.474

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=3 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study FSH	6.000 International units per Liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	0.267 International units per Liter Standard Deviation 0.3215	3.250 International units per Liter Standard Deviation 3.4648	0.850 International units per Liter Standard Deviation 2.4749
Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at End of Study LH	3.20 International units per Liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	1.70 International units per Liter Standard Deviation 1.473	3.55 International units per Liter Standard Deviation 2.333	3.55 International units per Liter Standard Deviation 4.738

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No male participants received Ambrisentan 2.5mg dose at the time of attaining 20 years of age, hence N=0; No endocrinology laboratory tests were performed for 5 mg dose at the 20-year visit, hence N=0.

FSH and LH level of participants were measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=1 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants FSH	—	—	2.350 International unit per Liter Standard Deviation 3.6062	0.500 International unit per Liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant
Change From Baseline in Plasma Endocrine Parameters - Male: FSH and LH at 20 Years of Age of Participants LH	—	—	2.90 International unit per Liter Standard Deviation 2.828	0.60 International unit per Liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No participants were analyzed for evaluation of Inhibin B in Ambrisentan 2.5 mg arm, hence N=0

Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=2 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at End of Study	—	15.0 Nanogram per liter Standard Deviation 5.66	8.5 Nanogram per liter Standard Deviation 6.36	73.0 Nanogram per liter Standard Deviation 175.36

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No male participants received Ambrisentan 2.5mg dose at the time of attaining 20 years of age, hence N=0; No endocrinology laboratory tests were performed for 5 mg dose at the 20-year visit, hence N=0.

Inhibin B level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=1 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Male: Inhibin B at 20 Years of Age of Participants	—	—	23.0 Nanogram per liter Standard Deviation 21.21	-47.0 Nanogram per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. At end of study, no participants were analyzed for evaluation of Sex harmone binding globulin in 2.5 mg dose, hence N=0

Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=2 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at End of Study	—	-28.5 Nanomoles per liter Standard Deviation 28.99	-11.5 Nanomoles per liter Standard Deviation 3.54	-11.0 Nanomoles per liter Standard Deviation 39.60

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No male participants received Ambrisentan 2.5mg dose at the time of attaining 20 years of age, hence N=0; No endocrinology laboratory tests were performed for 5 mg dose at the 20-year visit, hence N=0

Sex hormone binding globulin level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=1 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Male: Sex Hormone Binding Globulin at 20 Years of Age of Participants	—	—	-2.5 Nanomoles per liter Standard Deviation 12.02	12.0 Nanomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Total Testosterone level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=3 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at End of Study	10.650 Nanomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	2.900 Nanomoles per liter Standard Deviation 7.1190	7.300 Nanomoles per liter Standard Deviation 1.6971	17.175 Nanomoles per liter Standard Deviation 0.1061

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No male participants received Ambrisentan 2.5mg dose at the time of attaining 20 years of age, hence N=0; No endocrinology laboratory tests were performed for 5 mg dose at the 20-year visit, hence N=0.

Total Testosterone level of participants was measured. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=1 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Plasma Endocrine Parameters - Male: Total Testosterone at 20 Years of Age of Participants	—	—	4.000 Nanomoles per liter Standard Deviation 10.7480	6.600 Nanomoles per liter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No participants were analyzed for evaluation of testicular volume in 2.5 mg dose, hence N=0

Testicular volume was assessed by Prader's orchiodometer and the assessment was performed by a pediatric endocrinologist using the Tanner's criteria. Only those parameters having status - overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value. Data reported for left and right testicular volume.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=2 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study Right TV	—	0.0 Milliliter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	15.0 Milliliter Standard Deviation 7.07	11.5 Milliliter Standard Deviation 16.26
Change From Baseline of Pubertal Development in Male: Testicular Volume at End of Study Left TV	—	6.0 Milliliter Standard Deviation 8.49	16.5 Milliliter Standard Deviation 4.95	13.0 Milliliter Standard Deviation 14.14

PRIMARY outcome

Timeframe: Baseline (Day 1) and at 20 years of age of participants

Population: Safety Population. Only those participants with available data at the specified time points were analyzed. No participants were analyzed for evaluation of testicular volume in 2.5 mg dose, hence N=0

Testicular volume was assessed by Prader's orchiodometer and the assessment was performed by a pediatric endocrinologist using the Tanner's criteria. Only those parameters having status as overall were presented. Baseline was the last value recorded prior to start of study treatment from AMB112529.Change from Baseline was calculated by subtracting the Baseline value from the specified time point value. Only participants with data at 20 year visit is presented. When participants reached pubertal maturity prior to being 20 years of age then these tests were not repeated at 20-years of age of participants. Data reported for left and right testicular volume.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=1 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=1 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants Right TV	—	—	15.0 Milliliter Standard Deviation 7.07	8.0 Milliliter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant
Change From Baseline of Pubertal Development in Male: Testicular Volume at 20 Years of Age of Participants Left TV	—	17.0 Milliliter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	16.5 Milliliter Standard Deviation 4.95	8.0 Milliliter Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant

PRIMARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: Safety Population. Only those participants with available data at the specified time points were analyzed.

Time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, Phosphodiesterase type 5 [PDE-5] inhibitors) due to tolerability issues was defined as the time from randomization to the first occurrence of a dose change due to tolerability issues.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=2 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=1 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=3 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, Phosphodiesterase Type 5 [PDE-5] Inhibitors) Due to Tolerability Issues	393.0 Days Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	468.5 Days Standard Deviation 41.72	354.0 Days Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	1448.7 Days Standard Deviation 745.09

SECONDARY outcome

Timeframe: Up to 10 years and 11 months

Population: Safety Population.

Number of participants with all-cause death is presented.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=4 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=16 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=6 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=12 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Number of Participants With All-cause Death	0 Participants	4 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: ITT Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to their treatment group at the start of study AMB114588. Only those participants with available data at the specified time points were analyzed.

Participant's 6 MWD data has been presented into three categories as overall, with oxygen use and without oxygen use. The 6-minute walk test measures the distance that a participant can walk in 6 minutes. All participants were given standardized instructions and the distance walked was measured. Baseline which is the last value recorded prior to start of study treatment in AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=9 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=11 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=4 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=5 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test Overall	98.53 Meters Standard Deviation 115.355	56.74 Meters Standard Deviation 58.069	3.05 Meters Standard Deviation 94.659	34.24 Meters Standard Deviation 72.135
Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test With oxygen use	-13.05 Meters Standard Deviation 96.944	—	—	—
Change From Baseline in the 6 Minutes Walking Distance (6MWD) Test Without oxygen use	130.41 Meters Standard Deviation 104.115	56.74 Meters Standard Deviation 58.069	3.05 Meters Standard Deviation 94.659	34.24 Meters Standard Deviation 72.135

SECONDARY outcome

Timeframe: Up to 10 years and 11 months

Population: ITT Population. Only those participants with available data at the specified time points were analyzed.

Time to clinical worsening of PAH is defined as the time from randomization to first occurrence of death (all cause), placed on active list for lung transplant, and/or atrial septostomy, hospitalization due to PAH deterioration, addition of another targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition, change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition, PAH related deterioration identified by increase in WHO functional class, deterioration in exercise testing (i.e., 20% decrease in 6MWD on two consecutive tests -1 week apart, clinical signs or symptoms of right sided heart failure (i.e., new peripheral edema, increase in liver size, ascites, increase in jugular venous pressure, pericardial effusion, increased dyspnea).

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=2 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=5 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=3 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=1 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Time to the First Clinical Worsening of PAH	315.5 Days Standard Deviation 2.12	896.2 Days Standard Deviation 721.33	1122.0 Days Standard Deviation 704.09	228.0 Days Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant

SECONDARY outcome

Timeframe: Up to 10 years and 11 months

Population: ITT Population. Only those participants with available data at the specified time points were analyzed.

Time to addition of another targeted PAH therapeutics agents due to deterioration of clinical condition was defined as the time from randomization to the first occurrence of deterioration of clinical condition.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=1 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=2 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=1 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Deterioration of Clinical Condition	510.0 Days Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	697.5 Days Standard Deviation 863.38	909.0 Days Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	345.5 Days Standard Deviation 109.60

SECONDARY outcome

Timeframe: Up to 10 years and 11 months

Population: ITT Population. Only those participants with available data at the specified time points were analyzed. Participants in higher dose group (7.5 and 10 mg) were not taking any additional therapeutic PAH agent hence N=0.

The time to addition of another targeted PAH therapeutic agents due to lack of beneficial effect with previous therapy was defined as the time from randomization to the first occurrence of lack of beneficial effect with previous therapy (not reaching set treatment goals).

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=2 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=1 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Time to the Addition of Another Targeted PAH Therapeutic Agent Due to Lack of Beneficial Effect With Previous Therapy	315.5 Days Standard Deviation 2.12	173.0 Days Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	—	—

SECONDARY outcome

Timeframe: Up to 10 years and 11 months

Population: ITT Population. Only those participants with available data at the specified time points were analyzed.

Time to change in dose of ambrisentan or other targeted PAH therapeutic agents (prostanoids, PDE-5 inhibitors) due to deterioration of clinical condition was defined as the time from randomization to the first occurrence of a dose change due to deterioration of clinical condition.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=3 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=3 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=1 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=2 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Time to Change in Dose of Ambrisentan or Other Targeted PAH Therapeutic Agents (Prostanoids, PDE-5 Inhibitors) Due to Deterioration of Clinical Condition	1247.3 Days Standard Deviation 1051.97	1097.0 Days Standard Deviation 922.77	909.0 Days Standard Deviation NA NA indicates standard deviation could not be calculated due to single participant	345.5 Days Standard Deviation 109.60

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: ITT Population. Only those participants with available data at the specified time points were analyzed.

The short-form 10 (SF-10) Health Survey for children is a 10-item, 4-week recall, parent-completed health assessment that measures physical and psychosocial functioning for children ages five and over. Two summary scores were calculated: a Physical Summary Score (PHS) and a Psychosocial Summary Score (PSS) with a range of 5 to 30 points for each 5-item score. The aggregate score was then standardized and transformed to a norm-based scoring metric in accordance with the developer's guidelines. This generated the final standardized norm-based scores for PHS (range -10.90 to 57.21) and for PSS (range 8.81 to 62.28), respectively. A higher value on each summary score indicates better functioning. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=8 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=9 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=4 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=5 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children Physical health summary	-1.618 Scores on a scale Standard Deviation 7.4650	-0.967 Scores on a scale Standard Deviation 16.4890	-1.788 Scores on a scale Standard Deviation 12.0104	-0.272 Scores on a scale Standard Deviation 15.1029
Change From Baseline in Subject Global Assessment (SF-10) Health Survey for Children Psychosocial summary	-0.336 Scores on a scale Standard Deviation 5.4290	-1.880 Scores on a scale Standard Deviation 7.9810	2.225 Scores on a scale Standard Deviation 6.2357	6.766 Scores on a scale Standard Deviation 6.5080

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: ITT Population. Only those participants with available data at the specified time points were analyzed.

PAH was classified by WHO functional class (FC) at specific time points. There were four WHO FC grades based on severity of PAH symptoms (Class I=none, Class IV=most severe). Grades were mapped to numeric scale for which scores ranged from 1-4 (i.e. Class I=1 and IV=4). Change categorization was based on change from Baseline scores: -2, -1, 0, +1, +2. Data was categorized as No Change (0), Improved (-1,-2), Deteriorated (+1,+2). Baseline was the last value recorded prior to start of study treatment from AMB112529. Higher score indicated higher severity.Change from Baseline was calculated by subtracting the Baseline value from the end of study post-dose visit value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=9 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=11 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=4 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=5 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH Improved	5 Participants	5 Participants	3 Participants	0 Participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH No Change	4 Participants	6 Participants	1 Participants	5 Participants
Number of Participants With Change From Baseline in World Health Organization (WHO) Functional Class of PAH Deteriorated	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to 10 years and 11 months

Population: ITT Population. Only those participants with available data at the specified time points were analyzed.

Blood samples were collected to analyze NT-Pro BNP concentration at specific time points. Baseline was the last value recorded prior to start of study treatment from AMB112529. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.

Outcome measures

Measure	Ambrisentan 2.5 mg (Safety) n=7 Participants Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=11 Participants Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=2 Participants Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=5 Participants Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Percentage Change From Baseline in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) Concentration	-62.59 Percentage Change Interval -97.6 to 116.3	-56.02 Percentage Change Interval -99.0 to 2227.1	59.06 Percentage Change Interval -22.6 to 226.8	101.96 Percentage Change Interval -2.1 to 214.4

Adverse Events

Ambrisentan 2.5 mg (Safety)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Ambrisentan 5 mg (Safety)

Serious events: 7 serious events

Other events: 13 other events

Deaths: 4 deaths

Ambrisentan 7.5 mg (Safety)

Serious events: 4 serious events

Other events: 5 other events

Deaths: 1 deaths

Ambrisentan 10 mg (Safety)

Serious events: 8 serious events

Other events: 10 other events

Deaths: 2 deaths

Serious adverse events

Measure	Ambrisentan 2.5 mg (Safety) n=4 participants at risk Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=16 participants at risk Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=6 participants at risk Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=12 participants at risk Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Complication associated with device	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Acute right ventricular failure	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Atrioventricular block complete	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Atrioventricular block first degree	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Cardiac failure acute	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Conduction disorder	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Right ventricular failure	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Supraventricular tachycardia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Wandering pacemaker	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Congenital, familial and genetic disorders Autoimmune lymphoproliferative syndrome	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Gastric haemorrhage	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Vomiting	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Illness	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Non-cardiac chest pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Appendicitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations COVID-19	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Influenza	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Myringitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Otitis media acute	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Pneumonia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Sinusitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Alanine aminotransferase increased	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Metabolism and nutrition disorders Failure to thrive	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Scoliosis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Migraine	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Hyperventilation	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	25.0% 3/12 • Number of events 5 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Vascular disorders Hypotension	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Otitis media chronic	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).

Other adverse events

Measure	Ambrisentan 2.5 mg (Safety) n=4 participants at risk Participants received ambrisentan 2.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 5 mg (Safety) n=16 participants at risk Participants received ambrisentan 5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 7.5 mg (Safety) n=6 participants at risk Participants received ambrisentan 7.5 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	Ambrisentan 10 mg (Safety) n=12 participants at risk Participants received ambrisentan 10 mg tablet orally once daily. The Safety Population consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	18.8% 3/16 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Blood and lymphatic system disorders Lymphoid tissue hyperplasia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Blood and lymphatic system disorders Neutropenia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Angina pectoris	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Cardiac failure congestive	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Palpitations	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Cardiac disorders Pulmonary valve stenosis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Ear and labyrinth disorders Conductive deafness	25.0% 1/4 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Ear and labyrinth disorders Deafness	25.0% 1/4 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Ear and labyrinth disorders Ear congestion	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Ear and labyrinth disorders Ear haemorrhage	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Ear and labyrinth disorders Eustachian tube dysfunction	25.0% 1/4 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Ear and labyrinth disorders Motion sickness	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Ear and labyrinth disorders Vertigo	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Astigmatism	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Cataract	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Conjunctivitis allergic	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Eye pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Eye swelling	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Eyelid oedema	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Ocular hyperaemia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Strabismus	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Eye disorders Visual impairment	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Abdominal distension	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Abdominal pain lower	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Abdominal pain upper	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Aphthous ulcer	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Ascites	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Constipation	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Diarrhoea	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Dry mouth	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Dyspepsia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Gastritis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Nausea	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 5 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Stomatitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Tooth disorder	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Toothache	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Gastrointestinal disorders Vomiting	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Asthenia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Catheter site discharge	25.0% 1/4 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Catheter site pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Chest discomfort	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Chest pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Chills	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Fatigue	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Influenza like illness	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Localised oedema	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Non-cardiac chest pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Oedema peripheral	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Puncture site pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Pyrexia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
General disorders Swelling face	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Hepatobiliary disorders Hepatomegaly	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Immune system disorders Allergy to vaccine	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Immune system disorders Immunisation reaction	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Bronchitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 7 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Bronchitis viral	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Conjunctivitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Ear infection	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Epididymitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Folliculitis	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Gastroenteritis	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Gastroenteritis viral	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Herpes virus infection	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Hordeolum	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Influenza	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	18.8% 3/16 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Nasopharyngitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	31.2% 5/16 • Number of events 18 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	25.0% 3/12 • Number of events 9 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Oral candidiasis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Otitis externa	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Otitis media	25.0% 1/4 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Otitis media chronic	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Periodontitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Pharyngitis	25.0% 1/4 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	18.8% 3/16 • Number of events 4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Pharyngotonsillitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Pneumonia	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Respiratory tract infection	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Respiratory tract infection viral	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Rhinitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Sinusitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Tinea pedis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Tonsillitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 5 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Tooth infection	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Tracheobronchitis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Upper respiratory tract infection	50.0% 2/4 • Number of events 4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	18.8% 3/16 • Number of events 8 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	66.7% 4/6 • Number of events 7 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 5 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Urinary tract infection	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Viral infection	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Vulvovaginal candidiasis	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Animal bite	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Foot fracture	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Gingival injury	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Hand fracture	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Joint injury	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Limb injury	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Procedural pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Skin laceration	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Aspartate aminotransferase abnormal	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Aspartate aminotransferase increased	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Blood alkaline phosphatase increased	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Blood bilirubin increased	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Blood lactate dehydrogenase increased	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Blood parathyroid hormone increased	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Blood pressure diastolic decreased	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Haemoglobin decreased	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Transaminases increased	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Vitamin D decreased	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Investigations Weight decreased	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Metabolism and nutrition disorders Decreased appetite	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Metabolism and nutrition disorders Iron deficiency	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Bone cyst	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Coccydynia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Fistula	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Pain in jaw	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Sacral pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Dizziness	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Facial paralysis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Headache	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	18.8% 3/16 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 2/12 • Number of events 7 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Hypoaesthesia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Lethargy	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Petit mal epilepsy	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Presyncope	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Seizure	25.0% 1/4 • Number of events 5 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Somnolence	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Speech disorder	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Syncope	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Tardive dyskinesia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Nervous system disorders Tension headache	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Product Issues Device breakage	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Product Issues Device leakage	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Psychiatric disorders Abnormal behaviour	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Psychiatric disorders Automatism	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Psychiatric disorders Hallucination	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Psychiatric disorders Insomnia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Psychiatric disorders Panic attack	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Renal and urinary disorders Nephrolithiasis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Renal and urinary disorders Proteinuria	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Reproductive system and breast disorders Erection increased	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Adenoidal hypertrophy	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Nasal inflammation	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Nasal obstruction	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	18.8% 3/16 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Respiratory symptom	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	12.5% 2/16 • Number of events 3 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Tonsillar hypertrophy	25.0% 1/4 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Eczema	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Eczema asteatotic	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Erythema	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Lichen sclerosus	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Rash	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 2/6 • Number of events 2 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Surgical and medical procedures Therapeutic procedure	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Vascular disorders Cyanosis	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Vascular disorders Flushing	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Vascular disorders Hot flush	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Vascular disorders Hyperaemia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	8.3% 1/12 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Infections and infestations Pharyngitis streptococcal	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Injury, poisoning and procedural complications Ear procedural complication	25.0% 1/4 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/16 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	16.7% 1/6 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/12 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).
Blood and lymphatic system disorders Anaemia	0.00% 0/4 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	6.2% 1/16 • Number of events 1 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	0.00% 0/6 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).	33.3% 4/12 • Number of events 9 • All-cause mortality, non-STEAEs and STEAEs were collected from the start of study treatment up to 10 years and 11 months All-cause mortality, non-STEAEs and STEAEs were collected in Safety Population which consisted of all participants who received at least 1 dose of study drug. Participants were considered as belonging to the treatment group according to the highest dose received in the extension study (AMB114588).

Additional Information

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