Trial Outcomes & Findings for A Study of Multiple Doses of ALXN1210 in Healthy Adult Participants (NCT NCT05288673)

Last Updated: 2023-05-09

Results Overview

An adverse event (AE) was defined as any unfavorable and unintended sign (for example, including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or procedure, whether or not considered related to the medicinal product or procedure, which occurred during the course of the clinical study. TEAEs were defined as AEs that occurred on or after the date and time of study drug administration, or those that first occurred before dosing but worsened in frequency or severity after study drug administration. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

Baseline up to Day 309

Results posted on

2023-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1: ALXN1210 400 mg Participants received multiple doses of ALXN1210 400 milligrams (mg), via intravenous (IV) infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Overall Study STARTED	6	6	4
Overall Study Received At Least 1 Dose Of Study Drug	6	6	4
Overall Study COMPLETED	6	6	3
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: ALXN1210 400 mg Participants received multiple doses of ALXN1210 400 milligrams (mg), via intravenous (IV) infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Overall Study Consent withdrawn by subject	0	0	1

Baseline Characteristics

A Study of Multiple Doses of ALXN1210 in Healthy Adult Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=6 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled n=4 Participants Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Total n=16 Participants Total of all reporting groups
Age, Continuous	28.7 years STANDARD_DEVIATION 4.32 • n=5 Participants	35.2 years STANDARD_DEVIATION 5.78 • n=7 Participants	33.5 years STANDARD_DEVIATION 8.70 • n=5 Participants	32.3 years STANDARD_DEVIATION 6.44 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White	4 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to Day 309

Population: The safety population consisted of all participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=6 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled n=4 Participants Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	6 Participants	6 Participants	4 Participants

SECONDARY outcome

Timeframe: Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309

Population: The pharmacokinetic (PK) population consisted of all participants who had sufficient serum concentration data to enable the calculation of PK parameters. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure. Data was collected from the cohorts treated with ALXN1210 only for this Outcome Measure.

Blood samples were collected for estimation of AUCinf by noncompartmental analyses using Phoenix WinNonlin 6.3 or higher.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=5 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Area Under The Serum Concentration Versus Time Curve From Time Zero To Infinity (AUCinf) of ALXN1210	209047.941 hoursmicrograms/milliliter (hug/mL) Standard Deviation 34101.040	489692.330 hoursmicrograms/milliliter (hug/mL) Standard Deviation 58968.554	—

SECONDARY outcome

Timeframe: Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309

Population: The PK population consisted of all participants who had sufficient serum concentration data to enable the calculation of PK parameters. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure. Data was collected from the cohorts treated with ALXN1210 only for this Outcome Measure.

Blood samples were collected for estimation of AUCt by noncompartmental analyses using Phoenix WinNonlin 6.3 or higher.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=5 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Area Under The Serum Concentration From Time Zero To The Time of The Last Quantifiable Concentration (AUCt) of ALXN1210	205241.063 h*ug/mL Standard Deviation 32514.529	478063.379 h*ug/mL Standard Deviation 54295.251	—

SECONDARY outcome

Timeframe: Predose, end of infusion, 30 minutes, 4 hours, 8 hours and 24 hours post start of infusion on Day 1 up to Day 309

Blood samples were collected for estimation of Cmax by noncompartmental analyses using Phoenix WinNonlin 6.3 or higher.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=5 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Maximum Observed Serum Concentration (Cmax) of ALXN1210	210.333 ug/mL Standard Deviation 34.869	454.400 ug/mL Standard Deviation 50.639	—

SECONDARY outcome

Timeframe: Baseline, Day 113

Population: The pharmacodynamic (PD) population consisted of all participants who had sufficient total and/or free C5 concentration data, chicken red blood cells (cRBC) hemolysis data, or other data measuring C5 activation to enable the evaluation of the PD effects. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.

Blood samples were collected for analysis of free C5 concentration.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=5 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled n=4 Participants Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Percent Change From Baseline in Free Complement Protein C5 Concentration at Day 113	-31.63 Percent Change Standard Deviation 15.484	-93.8820 Percent Change Standard Deviation 11.2938	-22.16 Percent Change Standard Deviation 15.965

SECONDARY outcome

Timeframe: Baseline, Day 113

Population: The PD population consisted of all participants who had sufficient total and/or free C5 concentration data, cRBC hemolysis data, or other data measuring C5 activation to enable the evaluation of the PD effects. Here, Number of Participants analyzed signifies those participants who were evaluable for this outcome measure.

Blood samples were collected for analysis of total C5 concentration.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=5 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled n=4 Participants Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Percent Change From Baseline in Total C5 Concentration at Day 113	42.57 Percent Change Standard Deviation 28.445	154.36 Percent Change Standard Deviation 23.053	-8.65 Percent Change Standard Deviation 17.351

SECONDARY outcome

Timeframe: Baseline, Day 113

Blood samples were collected for analysis of cRBC hemolysis.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=5 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled n=4 Participants Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Percent Change From Baseline in Chicken Red Blood Cell Hemolysis at Day 113	-52.53 Percent Change Standard Deviation 22.740	-77.75 Percent Change Standard Deviation 28.579	-7.28 Percent Change Standard Deviation 21.259

SECONDARY outcome

Timeframe: Baseline, Day 113

Blood samples were collected for analysis of C5 activation. Results are reported as percent change in both the complement classical pathway (CCP) activity response and the complement alternative pathway (CAP) activity response.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=5 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled n=4 Participants Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Percent Change From Baseline in C5 Activation at Day 113 CCP	-1.66 Percent Change Standard Deviation 6.049	-15.16 Percent Change Standard Deviation 22.731	5.51 Percent Change Standard Deviation 10.839
Percent Change From Baseline in C5 Activation at Day 113 CAP	-17.54 Percent Change Standard Deviation 18.849	-39.76 Percent Change Standard Deviation 10.214	-5.90 Percent Change Standard Deviation 16.896

SECONDARY outcome

Timeframe: Baseline up to Day 309

Population: The immunogenicity analysis population consisted of all participants who had a pre-dose and post-dose ADA sample collected.

Blood samples were collected to evaluate antibody response through development of ADAs.

Outcome measures

Outcome measures
Measure	Cohort 1: ALXN1210 400 mg n=6 Participants Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=6 Participants Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled n=4 Participants Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Number of Participants With Positive Antidrug Antibodies (ADAs) to ALXN1210	0 Participants	0 Participants	1 Participants

Adverse Events

Cohort 1: ALXN1210 400 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Cohort 2: ALXN1210 800 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo: Pooled

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Alexion Pharmaceuticals, Inc.

Phone: 8557522356

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1: ALXN1210 400 mg n=6 participants at risk Participants received multiple doses of ALXN1210 400 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Cohort 2: ALXN1210 800 mg n=6 participants at risk Participants received multiple doses of ALXN1210 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.	Placebo: Pooled n=4 participants at risk Participants received multiple doses of placebo matched to ALXN1210 400 mg or 800 mg, via IV infusion on Day 1 and then every 28 days (Days 29, 57, 85, and 113) for a total of 4 doses. Participants were followed for 196 days.
Immune system disorders Seasonal allergy	16.7% 1/6 • Number of events 3 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
General disorders Fatigue	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 2 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
General disorders Influenza like illness	33.3% 2/6 • Number of events 7 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	25.0% 1/4 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
General disorders Injection site pain	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	25.0% 1/4 • Number of events 2 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Psychiatric disorders Anxiety	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	25.0% 1/4 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Foot fracture	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Head injury	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Muscle injury	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Injury, poisoning and procedural complications Tendon injury	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Cardiac disorders Dizziness	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Cardiac disorders Presyncope	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	33.3% 2/6 • Number of events 2 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	25.0% 1/4 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Nervous system disorders Dyskinesia	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Nervous system disorders Headache	66.7% 4/6 • Number of events 5 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	50.0% 3/6 • Number of events 5 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	50.0% 2/4 • Number of events 4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Nervous system disorders Presyncope	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	25.0% 1/4 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Eye disorders Eye pruritus	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Ear discomfort	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Ear and labyrinth disorders Tinnitus	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	25.0% 1/4 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Lip ulceration	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 2 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Gastrointestinal disorders Nausea	33.3% 2/6 • Number of events 4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	25.0% 1/4 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Muscle twitching	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Infections and infestations Folliculitis	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Infections and infestations Gastroenteritis	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Infections and infestations Herpes simplex	16.7% 1/6 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Infections and infestations Nasopharyngitis	33.3% 2/6 • Number of events 2 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	66.7% 4/6 • Number of events 4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	50.0% 2/4 • Number of events 3 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Infections and infestations Otitis externa	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	25.0% 1/4 • Number of events 1 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Infections and infestations Pharyngitis	0.00% 0/6 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	66.7% 4/6 • Number of events 4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.
Infections and infestations Viral upper respiratory tract infection	33.3% 2/6 • Number of events 2 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	33.3% 2/6 • Number of events 2 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.	0.00% 0/4 • Baseline up to Day 309 The safety population consisted of all participants who received at least 1 dose of study drug.