Trial Outcomes & Findings for A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension (NCT NCT03492177)

Last Updated: 2025-11-12

Results Overview

AUCτ, ss, combined was defined as the area under the plasma concentration-time curve over one dosing interval at steady state. AUCτ,ss,combined was calculated as 1/38 AUCτ,ss,selexipag plus 37/38 AUCτ,ss,ACT-333679.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Results posted on

2025-11-12

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1 (Greater Than or Equal to [>=] 12 Years to Less Than [<] 18 Years) Pediatric participants with pulmonary arterial hypertension (PAH) aged between \>=12 to \<18 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to individual maximum tolerated dose \[iMTD\] of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up titrated to the iMTD of 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 2 (>=6 to <12 Years) Pediatric participants with PAH aged between \>=6 to \<12 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 3 (>=2 to <6 Years) Pediatric participants with PAH aged between \>=2 to \<6 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.
Overall Study STARTED	22	21	20
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	22	21	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 (Greater Than or Equal to [>=] 12 Years to Less Than [<] 18 Years) Pediatric participants with pulmonary arterial hypertension (PAH) aged between \>=12 to \<18 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to individual maximum tolerated dose \[iMTD\] of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up titrated to the iMTD of 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 2 (>=6 to <12 Years) Pediatric participants with PAH aged between \>=6 to \<12 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 3 (>=2 to <6 Years) Pediatric participants with PAH aged between \>=2 to \<6 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.
Overall Study Adverse Event	1	0	0
Overall Study Death	3	0	3
Overall Study Lack of Efficacy	1	2	0
Overall Study Other	1	0	0
Overall Study Ongoing	16	19	17

Baseline Characteristics

A Clinical Study of to Confirm the Doses of Selexipag in Children With Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (Greater Than or Equal to [>=] 12 Years to Less Than [<] 18 Years) n=22 Participants Pediatric participants with pulmonary arterial hypertension (PAH) aged between \>=12 to \<18 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to individual maximum tolerated dose \[iMTD\] of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up titrated to the iMTD of 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 2 (>=6 to <12 Years) n=21 Participants Pediatric participants with PAH aged between \>=6 to \<12 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 3 (>=2 to <6 Years) n=20 Participants Pediatric participants with PAH aged between \>=2 to \<6 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Total n=63 Participants Total of all reporting groups
Age, Continuous	14.2 years STANDARD_DEVIATION 1.79 • n=10 Participants	8.5 years STANDARD_DEVIATION 1.36 • n=10 Participants	3.8 years STANDARD_DEVIATION 1.28 • n=20 Participants	9 years STANDARD_DEVIATION 4.53 • n=45 Participants
Sex: Female, Male Female	15 Participants n=10 Participants	11 Participants n=10 Participants	10 Participants n=20 Participants	36 Participants n=45 Participants
Sex: Female, Male Male	7 Participants n=10 Participants	10 Participants n=10 Participants	10 Participants n=20 Participants	27 Participants n=45 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	1 Participants n=45 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	18 Participants n=10 Participants	19 Participants n=10 Participants	19 Participants n=20 Participants	56 Participants n=45 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=10 Participants	2 Participants n=10 Participants	1 Participants n=20 Participants	6 Participants n=45 Participants
Race/Ethnicity, Customized Asian	3 Participants n=10 Participants	6 Participants n=10 Participants	7 Participants n=20 Participants	16 Participants n=45 Participants
Race/Ethnicity, Customized White	16 Participants n=10 Participants	12 Participants n=10 Participants	11 Participants n=20 Participants	39 Participants n=45 Participants
Race/Ethnicity, Customized Unknown or Not Reported	3 Participants n=10 Participants	2 Participants n=10 Participants	1 Participants n=20 Participants	6 Participants n=45 Participants
Race/Ethnicity, Customized Other	0 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants
Region of Enrollment BELARUS	4 Participants n=10 Participants	2 Participants n=10 Participants	3 Participants n=20 Participants	9 Participants n=45 Participants
Region of Enrollment BELGIUM	0 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=20 Participants	1 Participants n=45 Participants
Region of Enrollment CHINA	0 Participants n=10 Participants	1 Participants n=10 Participants	7 Participants n=20 Participants	8 Participants n=45 Participants
Region of Enrollment FRANCE	3 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	5 Participants n=45 Participants
Region of Enrollment GERMANY	0 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	1 Participants n=45 Participants
Region of Enrollment HUNGARY	1 Participants n=10 Participants	2 Participants n=10 Participants	2 Participants n=20 Participants	5 Participants n=45 Participants
Region of Enrollment ISRAEL	0 Participants n=10 Participants	1 Participants n=10 Participants	2 Participants n=20 Participants	3 Participants n=45 Participants
Region of Enrollment MALAYSIA	3 Participants n=10 Participants	4 Participants n=10 Participants	0 Participants n=20 Participants	7 Participants n=45 Participants
Region of Enrollment RUSSIAN FEDERATION	7 Participants n=10 Participants	0 Participants n=10 Participants	2 Participants n=20 Participants	9 Participants n=45 Participants
Region of Enrollment TAIWAN	0 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	1 Participants n=45 Participants
Region of Enrollment UKRAINE	1 Participants n=10 Participants	4 Participants n=10 Participants	0 Participants n=20 Participants	5 Participants n=45 Participants
Region of Enrollment UNITED KINGDOM	0 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants
Region of Enrollment UNITED STATES	1 Participants n=10 Participants	2 Participants n=10 Participants	0 Participants n=20 Participants	3 Participants n=45 Participants
Region of Enrollment Serbia	2 Participants n=10 Participants	1 Participants n=10 Participants	1 Participants n=20 Participants	4 Participants n=45 Participants

PRIMARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Population: The Pharmacokinetic analysis set included all participants from the safety set who complied with the protocol sufficiently and did not deviate from the protocol in a way that might affect the PK outcome of the study.

Outcome measures

Outcome measures
Measure	Cohort 1 (Greater Than or Equal to [>=] 12 Years to Less Than [<] 18 Years) n=21 Participants Pediatric participants with pulmonary arterial hypertension (PAH) aged between \>=12 to \<18 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to individual maximum tolerated dose \[iMTD\] of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up titrated to the iMTD of 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 2 (>=6 to <12 Years) n=21 Participants Pediatric participants with PAH aged between \>=6 to \<12 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 3 (>=2 to <6 Years) n=17 Participants Pediatric participants with PAH aged between \>=2 to \<6 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.
Area Under the Plasma Concentration-time Curve Over a Dose Interval at Steady State of Selexipag and Its Metabolite ACT-333679 Combined (AUCτ, ss, Combined)	21.56 nanograms*hour per milliliter Interval 17.32 to 26.84	20.40 nanograms*hour per milliliter Interval 16.83 to 24.73	18.57 nanograms*hour per milliliter Interval 15.16 to 22.74

SECONDARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 1,Week 12: pre-dose, 1, 2, 4, 6, 8 and 12 h post-morning dose. Week 2, 4 and 6: pre-dose (Up to Week 12)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 7 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+ 3 days (Up to Week 17)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: EOT+ 3 days (Up to Week 17)

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1 (Greater Than or Equal to [>=] 12 Years to Less Than [<] 18 Years)

Serious events: 12 serious events

Other events: 21 other events

Deaths: 3 deaths

Cohort 2 (>=6 to <12 Years)

Serious events: 4 serious events

Other events: 20 other events

Deaths: 0 deaths

Cohort 3 (>=2 to <6 Years)

Serious events: 6 serious events

Other events: 17 other events

Deaths: 3 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Scientist

Actelion Pharmaceuticals Ltd

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Cohort 1 (Greater Than or Equal to [>=] 12 Years to Less Than [<] 18 Years) n=22 participants at risk Pediatric participants with pulmonary arterial hypertension (PAH) aged between \>=12 to \<18 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to individual maximum tolerated dose \[iMTD\] of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up titrated to the iMTD of 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 2 (>=6 to <12 Years) n=21 participants at risk Pediatric participants with PAH aged between \>=6 to \<12 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.	Cohort 3 (>=2 to <6 Years) n=20 participants at risk Pediatric participants with PAH aged between \>=2 to \<6 years received Selexipag (Uptravi /ACT-293987/JNJ-67896049) orally on Day 1 based on body weight (\>=50 kilograms \[kg\] with a starting dose of 200 micrograms \[mcg\] and up-titrated to iMTD of up to 1,600 mcg; weight \>=25 to \<50 kg: with a starting dose of 150 mcg and up-titrated to the iMTD of up to 1200 mcg; weight \>=9 to \<25 kg at a starting dose of 100 mcg , up-titrated to the iMTD of up to 800 mcg) twice daily during the first 12 weeks. Up-titration was followed by a stable maintenance treatment period from Week 12 up to end of treatment.
Cardiac disorders Atrial Flutter	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Atrial Tachycardia	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Cardiac Arrest	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	10.0% 2/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Cardiac Failure Congestive	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Supraventricular Tachycardia	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Cardiac disorders Tachycardia	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Abdominal Pain	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Food Poisoning	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastritis	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	5.0% 1/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Gastrointestinal disorders Gastrooesophageal Reflux Disease	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
General disorders Death	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	5.0% 1/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
General disorders Non-Cardiac Chest Pain	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Bronchitis	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	5.0% 1/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Covid-19	18.2% 4/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 1/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Dengue Fever	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Pneumonia	13.6% 3/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 1/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	5.0% 1/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Pneumonia Aspiration	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	5.0% 1/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Pneumonia Mycoplasmal	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 1/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Respiratory Tract Infection	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 1/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 1/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Infections and infestations Urinary Tract Infection	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	5.0% 1/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Investigations Biopsy Kidney	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 1/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Myalgia	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Musculoskeletal and connective tissue disorders Trismus	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Brain Oedema	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Epilepsy	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 1/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Nervous system disorders Syncope	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	10.0% 2/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Renal and urinary disorders Focal Segmental Glomerulosclerosis	0.00% 0/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	4.8% 1/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Asthma	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Arterial Hypertension	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Hypertensive Crisis	9.1% 2/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	5.0% 1/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Suffocation Feeling	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.
Surgical and medical procedures Wisdom Teeth Removal	4.5% 1/22 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/21 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.	0.00% 0/20 • Up to 3 years 8 months The safety analysis set included all participants who received at least one dose of study treatment.