Trial Outcomes & Findings for Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1 (NCT NCT02706886)

Last Updated: 2020-01-30

Results Overview

An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

52 participants

Primary outcome timeframe

Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days

Results posted on

2020-01-30

Participant Flow

Participants were enrolled at ten sites in Germany, France, the United Kingdom, Israel, and the Netherlands.

In Part A, single ascending dose (SAD) part, healthy adults were dosed with lumasiran or placebo once. In Part B, multiple ascending doses (MAD) part, patients with primary hyperoxaluria type 1 (PH1) were dosed with lumasiran or placebo. All patients, who initially received placebo, received lumasiran after completing placebo dosing.

Participant milestones

Participant milestones
Measure	Part A: SAD: Placebo A single dose of matching placebo was administered subcutaneously (SC).	Part A: SAD: Lumasiran 0.3 mg/kg A single dose of 0.3 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg A single dose of 1.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg A single dose of 3.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Part A: SAD Period COMPLETED	8	6	6	4	6	0	0	0	0
Part A: SAD Period NOT COMPLETED	0	0	0	2	0	0	0	0	0
Part A: SAD Period STARTED	8	6	6	6	6	0	0	0	0
Part B: MAD Study Days 1-85 STARTED	0	0	0	0	0	3	7	7	3
Part B: MAD Study Days 1-85 COMPLETED	0	0	0	0	0	3	7	7	3
Part B: MAD Study Days 1-85 NOT COMPLETED	0	0	0	0	0	0	0	0	0
Part B: MAD Study Day 85-End of Study STARTED	0	0	0	0	0	0	8	8	4
Part B: MAD Study Day 85-End of Study COMPLETED	0	0	0	0	0	0	8	8	4
Part B: MAD Study Day 85-End of Study NOT COMPLETED	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: SAD: Placebo A single dose of matching placebo was administered subcutaneously (SC).	Part A: SAD: Lumasiran 0.3 mg/kg A single dose of 0.3 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg A single dose of 1.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg A single dose of 3.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Part A: SAD Period Withdrawal by Subject	0	0	0	2	0	0	0	0	0

Baseline Characteristics

Study of Lumasiran in Healthy Adults and Patients With Primary Hyperoxaluria Type 1

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: SAD: Placebo n=8 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=6 Participants A single dose of 6.0 mg/kg lumasiran was administered SC.	Part B: MAD: Placebo n=3 Participants Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=7 Participants Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM n=7 Participants Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M n=3 Participants Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Total n=52 Participants Total of all reporting groups
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Age, Continuous	29.8 years STANDARD_DEVIATION 6.25 • n=5 Participants	28.8 years STANDARD_DEVIATION 7.36 • n=7 Participants	30.2 years STANDARD_DEVIATION 7.81 • n=5 Participants	27.3 years STANDARD_DEVIATION 3.44 • n=4 Participants	28.8 years STANDARD_DEVIATION 5.46 • n=21 Participants	20.7 years STANDARD_DEVIATION 19.40 • n=10 Participants	14.0 years STANDARD_DEVIATION 9.93 • n=115 Participants	15.4 years STANDARD_DEVIATION 7.89 • n=24 Participants	9.7 years STANDARD_DEVIATION 5.51 • n=42 Participants	23.6 years STANDARD_DEVIATION 10.41 • n=42 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	5 Participants n=21 Participants	1 Participants n=10 Participants	6 Participants n=115 Participants	4 Participants n=24 Participants	2 Participants n=42 Participants	29 Participants n=42 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants	1 Participants n=115 Participants	3 Participants n=24 Participants	1 Participants n=42 Participants	23 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	3 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	3 Participants n=10 Participants	7 Participants n=115 Participants	7 Participants n=24 Participants	3 Participants n=42 Participants	49 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	2 Participants n=115 Participants	1 Participants n=24 Participants	0 Participants n=42 Participants	6 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	2 Participants n=42 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	2 Participants n=10 Participants	5 Participants n=115 Participants	5 Participants n=24 Participants	3 Participants n=42 Participants	40 Participants n=42 Participants

PRIMARY outcome

Timeframe: Part A (SAD): Up to 405 days; Part B (MAD): Up to 546 days

Population: Safety Analysis Set consisted of all healthy participants and patients, who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms.

An AE is any untoward medical occurrence in a clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=8 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=6 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo n=3 Participants Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=8 Participants Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM n=8 Participants Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M n=4 Participants Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Number of Participants With Adverse Events (AEs)	5 Participants	6 Participants	2 Participants	6 Participants	6 Participants	2 Participants	8 Participants	7 Participants	4 Participants

SECONDARY outcome

Timeframe: Part A (SAD): Day 1: predose, 30 minutes (min), 1 hour (h), 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h

Population: Pharmacokinetic (PK) Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data.

Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=6 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=8 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo n=8 Participants Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=4 Participants Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Maximum Concentration (Cmax) of Lumasiran in Plasma Day 1	39.7940 ng/mL Standard Deviation 8.58882	204.3748 ng/mL Standard Deviation 111.68091	533.4527 ng/mL Standard Deviation 160.11060	1176.1302 ng/mL Standard Deviation 199.89797	324.1386 ng/mL Standard Deviation 489.71104	582.4515 ng/mL Standard Deviation 266.90105	432.2798 ng/mL Standard Deviation 245.02660	—	—
Maximum Concentration (Cmax) of Lumasiran in Plasma Day 57	—	—	—	—	147.6780 ng/mL Standard Deviation 67.97968	701.1708 ng/mL Standard Deviation 511.63001	—	—	—
Maximum Concentration (Cmax) of Lumasiran in Plasma Day 85	—	—	—	—	—	—	411.5613 ng/mL Standard Deviation 174.92146	—	—

SECONDARY outcome

Timeframe: Part A (SAD): Day 1: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h and 24 h; Part B (MAD): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: predose, 30 min, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h

Population: PK Analysis Set consisted of all healthy participants and patients who received at least 1 dose of lumasiran and had at least 1 postdose sample for PK parameters and who had evaluable PK data.

Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=6 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=8 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo n=8 Participants Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=4 Participants Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Time to Cmax (Tmax) of Lumasiran in Plasma Day 1	5.0167 hours Interval 4.0 to 8.017	1.5000 hours Interval 0.517 to 8.0	3.0000 hours Interval 0.5 to 8.0	7.0000 hours Interval 0.5 to 8.067	3.9917 hours Interval 0.567 to 5.967	4.9917 hours Interval 0.533 to 12.0	9.0000 hours Interval 5.783 to 12.017	—	—
Time to Cmax (Tmax) of Lumasiran in Plasma Day 57	—	—	—	—	3.0417 hours Interval 0.5 to 6.0	2.9833 hours Interval 0.5 to 8.0	—	—	—
Time to Cmax (Tmax) of Lumasiran in Plasma Day 85	—	—	—	—	—	—	5.9833 hours Interval 4.05 to 7.95	—	—

SECONDARY outcome

Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=6 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=8 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo n=8 Participants Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=4 Participants Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma Day 1	293.5232 h*ng/mL Standard Deviation 96.86989	1899.8119 h*ng/mL Standard Deviation 558.25326	7211.5890 h*ng/mL Standard Deviation 1125.64173	16778.0579 h*ng/mL Standard Deviation 4380.15325	1428.0412 h*ng/mL Standard Deviation 697.85233	7400.2181 h*ng/mL Standard Deviation 2331.89843	6337.9082 h*ng/mL Standard Deviation 3840.03340	—	—
Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma Day 57	—	—	—	—	1608.1457 h*ng/mL Standard Deviation 708.95156	7959.7873 h*ng/mL Standard Deviation 1726.57675	—	—	—
Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Lumasiran in Plasma Day 85	—	—	—	—	—	—	5136.3462 h*ng/mL Standard Deviation 2757.90139	—	—

SECONDARY outcome

Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=2 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=2 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=1 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=4 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=5 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo n=1 Participants Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Terminal Half-life (t1/2) of Lumasiran in Plasma Day 1	7.0655 hours Standard Deviation 0.37379	5.9798 hours Standard Deviation 1.52471	3.4683 hours Standard Deviation NA SD was not calculated for arms with data for 1 participant.	3.2670 hours Standard Deviation 1.52759	5.4574 hours Standard Deviation 3.49432	7.8028 hours Standard Deviation NA SD was not calculated for arms with data for 1 participant.	—	—	—
Terminal Half-life (t1/2) of Lumasiran in Plasma Day 57	—	—	—	7.8090 hours Standard Deviation 4.52009	5.8356 hours Standard Deviation 3.12156	—	—	—	—
Terminal Half-life (t1/2) of Lumasiran in Plasma Day 85	—	—	—	—	—	4.6694 hours Standard Deviation NA SD was not calculated for arms with data for 1 participant.	—	—	—

SECONDARY outcome

Timeframe: Part A (SAD): Day 1: pooled urine 0-4 h, 4-8 h and 8-24 h; Part B (MAD): Part B (MAD phase): Days 1 and 57 for qM dosing and Days 1 and 85 for q3M dosing: pooled urine 0-4 h, 4-8 h, 8-12 h and 12-24 h

Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=6 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=5 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=8 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo n=7 Participants Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=4 Participants Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran Day 1	17.4219 percentage fractional excretion Standard Deviation 2.44129	19.0713 percentage fractional excretion Standard Deviation 3.88914	21.0472 percentage fractional excretion Standard Deviation 5.36667	25.7931 percentage fractional excretion Standard Deviation 3.25937	11.0895 percentage fractional excretion Standard Deviation 3.74207	11.1877 percentage fractional excretion Standard Deviation 6.07719	7.1691 percentage fractional excretion Standard Deviation 2.37465	—	—
Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran Day 57	—	—	—	—	9.4698 percentage fractional excretion Standard Deviation 4.21949	12.4604 percentage fractional excretion Standard Deviation 4.02897	—	—	—
Fraction Excreted in Urine in 24 Hours (Fe0-24) of Lumasiran Day 85	—	—	—	—	—	—	13.6938 percentage fractional excretion Standard Deviation 3.60004	—	—

SECONDARY outcome

Samples for Part A were collected only on Day 1; Part B on Days 1 and 57 for qM and on Days 1 and 85 for q3M arm groups.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=1 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=5 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=5 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=7 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo n=6 Participants Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=4 Participants Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Renal Clearance (CLR) of Lumasiran Day 1	8.7817 L/h Standard Deviation NA SD was not calculated for arms with data for 1 participant.	5.4906 L/h Standard Deviation 2.07402	5.8211 L/h Standard Deviation 1.31377	6.3417 L/h Standard Deviation 1.15497	2.2612 L/h Standard Deviation 1.17616	2.3818 L/h Standard Deviation 1.13067	2.0564 L/h Standard Deviation 1.20600	—	—
Renal Clearance (CLR) of Lumasiran Day 57	—	—	—	—	1.9610 L/h Standard Deviation 1.11228	2.5150 L/h Standard Deviation 0.80386	—	—	—
Renal Clearance (CLR) of Lumasiran Day 85	—	—	—	—	—	—	3.3663 L/h Standard Deviation 1.18371	—	—

SECONDARY outcome

Timeframe: Part A (SAD): Baseline, Part B (MAD): Baseline

Population: PD Analysis Set consisted of all participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood sample available that was evaluable for PD assessments. Due to an issue with plasma glycolate assay at the testing laboratory the data for Part B could not be calculated.

The pharmacodynamic (PD) outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=8 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=6 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Baseline Plasma Glycolate Concentration	5.1 umol/L Standard Deviation 1.73	5.3 umol/L Standard Deviation 1.51	5.7 umol/L Standard Deviation 1.97	6.2 umol/L Standard Deviation 2.56	4.8 umol/L Standard Deviation 1.72	—	—	—	—

SECONDARY outcome

Timeframe: Part A (SAD): Days 15, 29, 57 and 85; Part B (MAD): Days 15, 29, 57, 85

The PD outcome measure of plasma glycolate concentration could only be calculated for Part A. Due to an issue with the plasma glycolate assay at the testing laboratory the data for Part B could not be calculated.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=8 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=6 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Percentage Change From Baseline in Plasma Glycolate Concentration Day 15	18.3 percentage change from baseline Standard Deviation 67.19	58.3 percentage change from baseline Standard Deviation 55.29	48.5 percentage change from baseline Standard Deviation 82.99	56.4 percentage change from baseline Standard Deviation 28.50	59.5 percentage change from baseline Standard Deviation 49.00	—	—	—	—
Percentage Change From Baseline in Plasma Glycolate Concentration Day 29	22.4 percentage change from baseline Standard Deviation 46.83	32.9 percentage change from baseline Standard Deviation 57.67	70.6 percentage change from baseline Standard Deviation 82.74	146.4 percentage change from baseline Standard Deviation 81.99	390.1 percentage change from baseline Standard Deviation 270.40	—	—	—	—
Percentage Change From Baseline in Plasma Glycolate Concentration Day 57	126.7 percentage change from baseline Standard Deviation 242.68	66.3 percentage change from baseline Standard Deviation 38.07	109.8 percentage change from baseline Standard Deviation 124.29	230.1 percentage change from baseline Standard Deviation 180.36	730.4 percentage change from baseline Standard Deviation 439.54	—	—	—	—
Percentage Change From Baseline in Plasma Glycolate Concentration Day 85	31.2 percentage change from baseline Standard Deviation 131.04	15.6 percentage change from baseline Standard Deviation 100.54	40.7 percentage change from baseline Standard Deviation 110.75	196.2 percentage change from baseline Standard Deviation 152.41	731.3 percentage change from baseline Standard Deviation 375.02	—	—	—	—

SECONDARY outcome

Timeframe: Part A (SAD): Baseline

Population: PD Analysis Set for Part A consisted of all healthy participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments.

The endpoint was only measured in Part A.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=8 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=6 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Baseline Spot Urine Glycolate:Creatinine Ratio in Part A	12.4 mg/g Standard Deviation 4.63	15.7 mg/g Standard Deviation 4.27	15.7 mg/g Standard Deviation 3.14	13.0 mg/g Standard Deviation 3.52	14.8 mg/g Standard Deviation 4.31	—	—	—	—

SECONDARY outcome

Timeframe: Part A (SAD): Days 29 and 57

Population: PD Analysis Set in Part A consisted of all healthy participants who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments.

The endpoint was only measured in Part A.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=8 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=6 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=6 Participants A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A Day 29	8.1 percentage change from baseline Standard Deviation 43.42	32.5 percentage change from baseline Standard Deviation 22.6	82.9 percentage change from baseline Standard Deviation 65.00	109.1 percentage change from baseline Standard Deviation 66.51	210.5 percentage change from baseline Standard Deviation 199.30	—	—	—	—
Percentage Change From Baseline in Spot Urine Glycolate:Creatinine Ratio in Part A Day 57	73.8 percentage change from baseline Standard Deviation 108.9	38.0 percentage change from baseline Standard Deviation 50.62	47.8 percentage change from baseline Standard Deviation 41.03	215.0 percentage change from baseline Standard Deviation 178.72	310.7 percentage change from baseline Standard Deviation 94.51	—	—	—	—

SECONDARY outcome

Timeframe: Part B (MAD): Baseline

Population: PD Analysis Set in Part B consisted of all patients with PH1 who received at least 1 dose of study drug (lumasiran, placebo) and had at least 1 postdose blood and/or urine sample available that was evaluable for PD assessments.

The endpoint was only measured in Part B.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=3 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=8 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=8 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=4 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B	1.96 mmol/24h/1.73m^2 Standard Deviation 0.321	1.73 mmol/24h/1.73m^2 Standard Deviation 0.696	1.84 mmol/24h/1.73m^2 Standard Deviation 0.621	1.30 mmol/24h/1.73m^2 Standard Deviation 0.350	—	—	—	—	—

SECONDARY outcome

Timeframe: Part B (MAD): 24 hour urine collections on Days 29, 57, 85, 113, 141, 169, 197

The endpoint was only measured in Part B.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=2 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=8 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=8 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=4 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B Day 141	—	-64.6 percentage change from baseline Standard Deviation 13.55	-73.5 percentage change from baseline Standard Deviation 8.11	-68.4 percentage change from baseline Standard Deviation 3.21	—	—	—	—	—
Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B Day 29	-2.4 percentage change from baseline Standard Deviation NA SD was not calculated for arms with data for 1 participant.	-41.1 percentage change from baseline Standard Deviation 24.76	-57.5 percentage change from baseline Standard Deviation 10.84	-49.2 percentage change from baseline Standard Deviation 5.40	—	—	—	—	—
Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B Day 57	-27.8 percentage change from baseline Standard Deviation 47.11	-49.7 percentage change from baseline Standard Deviation 20.08	-72.5 percentage change from baseline Standard Deviation 10.70	-49.1 percentage change from baseline Standard Deviation 5.82	—	—	—	—	—
Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B Day 85	9.1 percentage change from baseline Standard Deviation NA SD was not calculated for arms with data for 1 participant.	-65.6 percentage change from baseline Standard Deviation 16.64	-68.4 percentage change from baseline Standard Deviation 10.60	-53.3 percentage change from baseline Standard Deviation 3.66	—	—	—	—	—
Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B Day 113	—	-61.4 percentage change from baseline Standard Deviation 12.24	-78.1 percentage change from baseline Standard Deviation 7.80	-59.1 percentage change from baseline Standard Deviation 20.75	—	—	—	—	—
Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B Day 169	—	-61.6 percentage change from baseline Standard Deviation 14.19	-69.3 percentage change from baseline Standard Deviation 9.61	-48.7 percentage change from baseline Standard Deviation 14.19	—	—	—	—	—
Percentage Change From Baseline of 24 Hour Urine Oxalate Corrected for BSA in Part B Day 197	—	-63.8 percentage change from baseline Standard Deviation 13.85	-71.2 percentage change from baseline Standard Deviation 11.70	-52.7 percentage change from baseline Standard Deviation 6.38	—	—	—	—	—

SECONDARY outcome

Timeframe: Part B (MAD): Baseline

The endpoint was only measured during the initial 85 days in Part B.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=3 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=7 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=7 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=3 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Baseline 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days	193 mg/g Standard Deviation 117.2	241 mg/g Standard Deviation 85.6	289 mg/g Standard Deviation 146.0	281 mg/g Standard Deviation 139.0	—	—	—	—	—

SECONDARY outcome

Timeframe: Part B (MAD): 24 hour urine collections on Days 29, 57 and 85

The endpoint was only measured during the initial 85 days in Part B.

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=3 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=7 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=7 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=3 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days Day 29	-15.1 percentage change from baseline Standard Deviation 6.47	53.1 percentage change from baseline Standard Deviation 42.18	31.4 percentage change from baseline Standard Deviation 35.99	33.0 percentage change from baseline Standard Deviation 36.37	—	—	—	—	—
Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days Day 57	-13.8 percentage change from baseline Standard Deviation 29.02	82.3 percentage change from baseline Standard Deviation 40.12	42.3 percentage change from baseline Standard Deviation 57.56	81.8 percentage change from baseline Standard Deviation 35.66	—	—	—	—	—
Percentage Change From Baseline of 24 Hour Urine Glycolate:Creatinine Ratio in Part B - Initial 85 Days Day 85	-23.0 percentage change from baseline Standard Deviation 10.45	71.0 percentage change from baseline Standard Deviation 55.62	43.7 percentage change from baseline Standard Deviation 62.15	42.0 percentage change from baseline Standard Deviation 20.86	—	—	—	—	—

SECONDARY outcome

Timeframe: Part B (MAD): Baseline

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=3 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=8 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=8 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=4 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Baseline Creatinine Clearance Corrected for BSA in Part B	64.389 mL/min/1.73 m^2 Standard Deviation 19.8024	108.149 mL/min/1.73 m^2 Standard Deviation 44.1783	86.268 mL/min/1.73 m^2 Standard Deviation 22.1226	88.251 mL/min/1.73 m^2 Standard Deviation 30.0118	—	—	—	—	—

SECONDARY outcome

Timeframe: Part B (MAD): Days 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337, 365, 393, 421, 449

Outcome measures

Outcome measures
Measure	Part A: SAD: Placebo n=2 Participants A single dose of matching placebo was administered SC.	Part A: SAD: Lumasiran 0.3 mg/kg n=8 Participants A single dose of 0.3 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 1.0 mg/kg n=8 Participants A single dose of 1.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=4 Participants A single dose of 3.0 mg/kg Lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg A single dose of 6.0 mg/kg Lumasiran was administered SC.	Part B: MAD: Placebo Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in Part B: MAD Study Day 85-End of Study and were then treated with lumasiran. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg qM Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.	Part B: MAD: Lumasiran 3.0 mg/kg q3M Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days. One participant from the Part B: MAD: Placebo arm crossed over to this lumasiran arm at Day 85. For this participant treatment with lumasiran started at Day 85.
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 57	20.184 percentage change from baseline Standard Deviation 23.5572	-8.426 percentage change from baseline Standard Deviation 19.7271	4.505 percentage change from baseline Standard Deviation 35.2457	37.030 percentage change from baseline Standard Deviation 56.1210	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 141	—	-8.804 percentage change from baseline Standard Deviation 27.4802	9.315 percentage change from baseline Standard Deviation 27.5044	-30.691 percentage change from baseline Standard Deviation 12.8912	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 29	9.019 percentage change from baseline Standard Deviation NA Standard Deviation is not calculated for arms with one participant	-6.672 percentage change from baseline Standard Deviation 11.9614	-0.624 percentage change from baseline Standard Deviation 15.1771	2.748 percentage change from baseline Standard Deviation 5.6858	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 85	-5.945 percentage change from baseline Standard Deviation NA Standard Deviation is not calculated for arms with one participant	-13.536 percentage change from baseline Standard Deviation 22.8679	-3.720 percentage change from baseline Standard Deviation 22.6231	-6.113 percentage change from baseline Standard Deviation 43.5441	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 113	—	-14.424 percentage change from baseline Standard Deviation 24.1107	3.444 percentage change from baseline Standard Deviation 29.6749	7.570 percentage change from baseline Standard Deviation 40.5928	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 169	—	-19.796 percentage change from baseline Standard Deviation 31.7492	-8.544 percentage change from baseline Standard Deviation 14.8481	20.210 percentage change from baseline Standard Deviation NA Standard Deviation is not calculated for arms with one participant	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 197	—	-8.546 percentage change from baseline Standard Deviation 13.5672	-13.513 percentage change from baseline Standard Deviation 25.0560	28.857 percentage change from baseline Standard Deviation 22.1891	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 225	—	-18.221 percentage change from baseline Standard Deviation 14.2322	29.013 percentage change from baseline Standard Deviation 53.5563	-14.964 percentage change from baseline Standard Deviation 9.9130	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 253	—	-5.140 percentage change from baseline Standard Deviation 19.2839	10.232 percentage change from baseline Standard Deviation 24.4929	—	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 281	—	-14.283 percentage change from baseline Standard Deviation 22.6126	5.841 percentage change from baseline Standard Deviation 13.0381	—	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 309	—	-0.403 percentage change from baseline Standard Deviation 34.6839	8.441 percentage change from baseline Standard Deviation 11.5329	—	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 337	—	-5.168 percentage change from baseline Standard Deviation 31.0756	8.688 percentage change from baseline Standard Deviation 24.2094	—	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 365	—	2.268 percentage change from baseline Standard Deviation 33.7565	9.201 percentage change from baseline Standard Deviation 14.4856	—	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 393	—	-11.942 percentage change from baseline Standard Deviation 45.3027	-4.484 percentage change from baseline Standard Deviation 12.6320	—	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 421	—	7.610 percentage change from baseline Standard Deviation 11.2195	-6.498 percentage change from baseline Standard Deviation 12.9022	—	—	—	—	—	—
Percentage Change From Baseline of Creatinine Clearance Corrected for BSA in Part B Day 449	—	—	-15.093 percentage change from baseline Standard Deviation 10.3705	—	—	—	—	—	—

Adverse Events

Part A: SAD: Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part A: SAD: Lumasiran 0.3 mg/kg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part A: SAD: Lumasiran 1.0 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A: SAD: Lumasiran 3.0 mg/kg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part A: SAD: Lumasiran 6.0 mg/kg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part B: MAD: Placebo

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B: MAD: Lumasiran 1.0 mg/kg qM

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Part B: MAD: Lumasiran 3.0 mg/kg qM

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Part B: MAD: Lumasiran 3.0 mg/kg q3M

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A: SAD: Placebo n=8 participants at risk A single dose of matching placebo was administered.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 participants at risk A single dose of 0.3 mg/kg lumasiran was administered subcutaneously (SC).	Part A: SAD: Lumasiran 1.0 mg/kg n=6 participants at risk A single dose of 1.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 participants at risk A single dose of 3.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=6 participants at risk A single dose of 6.0 mg/kg lumasiran was administered SC.	Part B: MAD: Placebo n=3 participants at risk Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in the All-Lumasiran-Treated Period. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=8 participants at risk Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 3.0 mg/kg qM n=8 participants at risk Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 3.0 mg/kg q3M n=4 participants at risk Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days.
Gastrointestinal disorders Vomiting	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 2/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Renal and urinary disorders Nephrolithiasis	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 1/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Pyelonephritis acute	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 1/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Abdominal pain	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Pyrexia	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Gastroenteritis	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.

Other adverse events

Other adverse events
Measure	Part A: SAD: Placebo n=8 participants at risk A single dose of matching placebo was administered.	Part A: SAD: Lumasiran 0.3 mg/kg n=6 participants at risk A single dose of 0.3 mg/kg lumasiran was administered subcutaneously (SC).	Part A: SAD: Lumasiran 1.0 mg/kg n=6 participants at risk A single dose of 1.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 3.0 mg/kg n=6 participants at risk A single dose of 3.0 mg/kg lumasiran was administered SC.	Part A: SAD: Lumasiran 6.0 mg/kg n=6 participants at risk A single dose of 6.0 mg/kg lumasiran was administered SC.	Part B: MAD: Placebo n=3 participants at risk Participants with primary hyperoxaluria type 1 (PH1) were treated with placebo matching one of the lumasiran dosages in the lumasiran arms (one placebo participant for each lumasiran arm). At Day 85 these placebo-treated participants crossed over to their respective Part B lumasiran arms in the All-Lumasiran-Treated Period. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 1.0 mg/kg qM n=8 participants at risk Participants with PH1 were treated with 1.0 mg/kg lumasiran SC once monthly (qM) on Days 1, 29 and 57. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 3.0 mg/kg qM n=8 participants at risk Participants with PH1 were treated with 3.0 mg/kg lumasiran SC qM on Days 1, 29 and 57. The estimated total time on study was up to 546 days.	Part B: MAD: Lumasiran 3.0 mg/kg q3M n=4 participants at risk Participants with PH1 were treated with 3.0 mg/kg lumasiran SC once every three months (q3M) on Days 1 and 85. The estimated total time on study was up to 546 days.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Abdominal pain	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	37.5% 3/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 1/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Diarrhoea	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Faeces soft	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Flatulence	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Nausea	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Fatigue	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 2/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Injection site pain	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	66.7% 4/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Gastroenteritis	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 2/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Influenza	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Nasopharyngitis	37.5% 3/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	66.7% 4/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	66.7% 4/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	50.0% 2/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Periodontitis	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Sinusitis	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Tonsillitis	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Upper respiratory tract infection	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Urinary tract infection	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Viral pharyngitis	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 1/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Injury, poisoning and procedural complications Contusion	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 1/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Injury, poisoning and procedural complications Head injury	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Injury, poisoning and procedural complications Laceration	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Injury, poisoning and procedural complications Tendon injury	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Investigations Alanine aminotransferase increased	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Investigations Aspartate aminotransferase increased	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Investigations Blood creatine phosphokinase increased	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Nervous system disorders Headache	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 2/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	50.0% 3/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 2/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 2/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Nervous system disorders Migraine	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Nervous system disorders Presyncope	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Psychiatric disorders Alcoholic hangover	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Skin and subcutaneous tissue disorders Papule	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Skin and subcutaneous tissue disorders Rash follicular	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Skin and subcutaneous tissue disorders Skin texture abnormal	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Social circumstances Caffeine consumption	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	16.7% 1/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Blood and lymphatic system disorders Lymph node pain	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Eye disorders Visual impairment	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Constipation	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 1/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Toothache	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Vomiting	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 1/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 1/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Injection site bruising	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Injection site erythema	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Injection site pruritus	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Pyrexia	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	33.3% 1/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 1/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Pharyngitis	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Rhinitis	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	37.5% 3/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Urinary tract infection enterococcal	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Renal and urinary disorders Dysuria	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Renal and urinary disorders Nephrolithiasis	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	37.5% 3/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 2/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Congenital, familial and genetic disorders Atrial septal defect	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Eye disorders Dry eye	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Eye disorders Eye swelling	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Gastrointestinal disorders Teething	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 1/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Axillary pain	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Influenza like illness	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Injection site discolouration	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
General disorders Injection site swelling	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Body tinea	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Dermatitis infected	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Urinary tract infection bacterial	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Infections and infestations Urinary tract infection staphylococcal	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Injury, poisoning and procedural complications Soft tissue injury	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Investigations Blood phosphorus decreased	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 1/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Metabolism and nutrition disorders Gout	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 1/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Metabolism and nutrition disorders Increased appetite	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Metabolism and nutrition disorders Overweight	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 1/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Nervous system disorders Lethargy	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	25.0% 1/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Skin and subcutaneous tissue disorders Blister	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Skin and subcutaneous tissue disorders Rash	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.
Cardiac disorders Tricuspid valve incompetence	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/6 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/3 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	12.5% 1/8 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.	0.00% 0/4 • Part A (SAD phase): Up to 405 days; Part B (MAD phase): Up to 546 days Safety Analysis Set consisted of all healthy participants and patients who received at least 1 dose of study drug (lumasiran, placebo), grouped according to actual treatment received. Part B participants who crossed over from placebo to the lumasiran arms are included in the placebo arm as well as lumasiran arms and adverse events are reported based on the treatment received at the time of the event.

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals Inc

Phone: 866-330-0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60