Trial Outcomes & Findings for Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy (NCT NCT01737398)

Last Updated: 2019-07-17

Results Overview

The mNIS+7 composite score is a measure of neurologic impairment that evaluates muscle weakness, sensation, reflexes, nerve conduction, and autonomic function. The mNIS+7 Composite Score has a range of -22.32 to 346.32 and a higher mNIS+7 composite score indicates lower function.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

173 participants

Primary outcome timeframe

Baseline and Week 66

Results posted on

2019-07-17

Participant Flow

Participants randomized: 113 inotersen and 60 placebo; received study treatment: 112 inotersen and 60 placebo. This study consisted of a 65-week Treatment Period, 1-week End of Treatment (EOT) Period, and a 6-month Post-treatment Evaluation Period.

Participant milestones

Participant milestones
Measure	Inotersen Participants received 3 subcutaneous (SC) doses of 300 milligrams (mg) inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Overall Study STARTED	113	60
Overall Study Received at Least 1 Dose of Study Drug	112	60
Overall Study Safety Set	112	60
Overall Study COMPLETED	87	52
Overall Study NOT COMPLETED	26	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Inotersen Participants received 3 subcutaneous (SC) doses of 300 milligrams (mg) inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Overall Study Adverse event or SAE	16	1
Overall Study Stopping rule met	2	1
Overall Study Voluntary withdrawal	2	3
Overall Study Ineligibility	1	0
Overall Study Liver transplant	1	0
Overall Study Disease progression	2	3
Overall Study Sponsor's decision	2	0

Baseline Characteristics

Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inotersen n=112 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=60 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.	Total n=172 Participants Total of all reporting groups
Age, Continuous	59.0 years STANDARD_DEVIATION 12.53 • n=5 Participants	59.5 years STANDARD_DEVIATION 14.05 • n=7 Participants	59.2 years STANDARD_DEVIATION 13.04 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	19 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	77 Participants n=5 Participants	41 Participants n=7 Participants	118 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	7 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	95 Participants n=5 Participants	53 Participants n=7 Participants	148 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Black	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized White	105 Participants n=5 Participants	53 Participants n=7 Participants	158 Participants n=5 Participants
Race/Ethnicity, Customized White & Grayish-Brown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Participants diagnosed with hATTR-CM Yes	45 Participants n=5 Participants	22 Participants n=7 Participants	67 Participants n=5 Participants
Participants diagnosed with hATTR-CM No	67 Participants n=5 Participants	38 Participants n=7 Participants	105 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 66

Population: The full analysis set included all randomized participants who received at least 1 injection of study drug (inotersen or placebo) and who had a Baseline and at least 1 post-Baseline efficacy assessment for the mNIS+7 score or Norfolk QoL-DN questionnaire total score. Participants analyzed = participants with evaluable data.

Outcome measures

Outcome measures
Measure	Inotersen n=85 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=52 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline In The Modified Neuropathy Impairment Score (mNIS) +7 Composite Score at Week 66	4.16 Scores on a Scale Standard Deviation 15.672	23.89 Scores on a Scale Standard Deviation 24.190

PRIMARY outcome

Timeframe: Baseline and Week 66

The Norfolk QoL-DN score is a measure of physical function/large fiber neuropathy, symptoms, activities of daily living, small fiber neuropathy, and autonomic neuropathy. The Norfolk QoL-DN total score has a range of -4 to 136, and a higher Norfolk QoL-DN score indicates poorer QoL.

Outcome measures

Outcome measures
Measure	Inotersen n=84 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=52 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline In The Norfolk Quality Of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66	-0.08 Scores on a Scale Standard Deviation 18.967	10.77 Scores on a Scale Standard Deviation 21.134

SECONDARY outcome

Timeframe: Baseline and Week 66

Population: This endpoint only measured participants with Stage 1 hATTR-PN in Full Analysis Set. Participants analyzed = participants with evaluable data.

The Norfolk QoL-DN symptoms score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN symptoms domain score has a range of 0-32, and a higher Norfolk QoL-DN score indicates poorer QoL.

Outcome measures

Outcome measures
Measure	Inotersen n=55 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=33 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline In The Norfolk QoL-DN Questionnaire Symptoms Domain Score at Week 66	-1.40 Scores on a Scale Standard Deviation 4.763	1.18 Scores on a Scale Standard Deviation 5.270

SECONDARY outcome

Timeframe: Baseline and Week 66

Population: This endpoints only measured participants who had Stage 2 hATTR-PN in Full Analysis Set. Participants analyzed = participants with evaluable data.

The Norfolk QoL-DN physical functioning/large fiber neuropathy domain score is a sub-score of the total Norfolk QoL-DN Questionnaire. The Norfolk QoL-DN physical function/large fiber neuropathy domain score has a range of -4 to 56, and a higher Norfolk QoL-DN domain score indicates poorer QoL.

Outcome measures

Outcome measures
Measure	Inotersen n=29 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=19 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline In The Norfolk QoL-DN Questionnaire Physical Functioning/Large Fiber Neuropathy Domain Score at Week 66	1.05 Scores on a Scale Standard Deviation 11.924	8.74 Scores on a Scale Standard Deviation 9.689

SECONDARY outcome

Timeframe: Baseline and Week 65

The mBMI is the BMI multiplied by the serum albumin g/L

Outcome measures

Outcome measures
Measure	Inotersen n=82 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=49 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline In Modified Body Mass Index (mBMI) at Week 65	-73.32 kg/m^2*g/L Standard Deviation 96.311	-85.21 kg/m^2*g/L Standard Deviation 91.259

SECONDARY outcome

Timeframe: Baseline and Week 65

Outcome measures

Outcome measures
Measure	Inotersen n=82 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=49 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline In Body Mass Index (BMI) at Week 65	-0.24 kg/m^2 Standard Deviation 1.521	-0.87 kg/m^2 Standard Deviation 1.202

SECONDARY outcome

Timeframe: Baseline and Week 66

The NIS score is a measure of neurologic impairment. The NIS Score has a range of 0 to 244 and a higher NIS score indicates lower function.

Outcome measures

Outcome measures
Measure	Inotersen n=85 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=52 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline in Neuropathy Impairment Score (NIS) at Week 66	4.47 Scores on a Scale Standard Deviation 10.329	17.29 Scores on a Scale Standard Deviation 16.986

SECONDARY outcome

Timeframe: Baseline and Week 66

The Modified +7 score is a version of the NIS score that is a measure of neurologic impairment. The Modified +7 Score has a range of -22.32 to 102.32 and a higher NIS score indicates lower function.

Outcome measures

Outcome measures
Measure	Inotersen n=85 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=52 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline in Modified +7 at Week 66	-0.31 Scores on a Scale Standard Deviation 11.134	6.60 Scores on a Scale Standard Deviation 12.770

SECONDARY outcome

Timeframe: Baseline and Week 66

The NIS+7 score is a version of the NIS score that is a measure of neurologic impairment. The NIS+7 Score has a range of -26.04 to 270.04 and a higher NIS score indicates lower function.

Outcome measures

Outcome measures
Measure	Inotersen n=85 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=52 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline in NIS+7 at Week 66	5.10 Scores on a Scale Standard Deviation 10.709	19.00 Scores on a Scale Standard Deviation 16.824

SECONDARY outcome

Timeframe: Baseline and Week 65

Population: The CM-ECHO Set includes the subset of the Randomized Set who had a diagnosis of TTR cardiomyopathy at study entry but are not in the ECHO subgroup, plus participants who qualified to participate in the ECHO subgroup (whether consented or not). Participants analyzed = participants with evaluable data.

GLS by ECHO is a measure of cardiac systolic function

Outcome measures

Outcome measures
Measure	Inotersen n=50 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=25 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram (ECHO) at Week 65 in the CM-ECHO Set	0.69 Percent Change Standard Deviation 3.134	0.46 Percent Change Standard Deviation 2.702

SECONDARY outcome

Timeframe: Baseline and Week 65

GLS by ECHO is a measure of cardiac systolic function

Outcome measures

Outcome measures
Measure	Inotersen n=30 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=16 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline in Global Longitudinal Strain (GLS) by Echocardiogram ECHO at Week 65 in the ECHO Subgroup	0.25 Percent Change Standard Deviation 3.163	1.05 Percent Change Standard Deviation 2.745

SECONDARY outcome

Timeframe: Baseline and Week 65

Outcome measures

Outcome measures
Measure	Inotersen n=84 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=51 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline in Transthyretin (TTR) Level at Week 65	-0.1570 g/L Standard Deviation 0.0619	-0.0146 g/L Standard Deviation 0.0402

SECONDARY outcome

Timeframe: Baseline and Week 65

Outcome measures

Outcome measures
Measure	Inotersen n=83 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=51 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Change From Baseline in Retinol Binding Protein 4 (RBP4) Level at Week 65	-21725.9 ug/L Standard Deviation 9884.04	-1768.7 ug/L Standard Deviation 8027.78

SECONDARY outcome

Timeframe: Week 65

Population: The PK Set was defined as all randomized participants who received at least 1 dose of active study drug (inotersen) and had at least 1 evaluable PK sample collected and analyzed with a reportable result.

Outcome measures

Outcome measures
Measure	Inotersen n=5 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=3 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Maximum Measured Plasma Concentration (Cmax) Of Inotersen At Week 65	6.76 ug/mL Standard Deviation 1.88	11.1 ug/mL Standard Deviation 4.80

SECONDARY outcome

Timeframe: Week 65

Outcome measures

Outcome measures
Measure	Inotersen n=5 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=3 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Time To The Maximum Plasma Concentration (Tmax) Of Inotersen At Week 65	4.14 hours Standard Deviation 1.88	3.48 hours Standard Deviation 0.68

SECONDARY outcome

Timeframe: Week 65

Outcome measures

Outcome measures
Measure	Inotersen n=5 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=3 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Area Under The Plasma Concentration-time Curve From 0 To 24 Hours (AUC[0-24hr]) Of Inotersen At Week 65	93.1 ug*hr/mL Standard Deviation 30.7	92.4 ug*hr/mL Standard Deviation 77.3

SECONDARY outcome

Timeframe: Week 65

Outcome measures

Outcome measures
Measure	Inotersen n=4 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=3 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Area Under The Plasma Concentration-time Curve From 0 To 168 Hours (AUC[0-168hr]) Of Inotersen At Week 65	98.9 ug*hr/mL Standard Deviation 33.5	103.0 ug*hr/mL Standard Deviation 88.2

SECONDARY outcome

Timeframe: Week 65

Outcome measures

Outcome measures
Measure	Inotersen n=5 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=3 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Plasma Clearance From 0 To 24 Hours (CL[0-24hr]/F) Of Inotersen At Week 65	3.57 L/hr Standard Deviation 1.32	6.14 L/hr Standard Deviation 5.92

SECONDARY outcome

Timeframe: Week 65

Outcome measures

Outcome measures
Measure	Inotersen n=4 Participants Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=3 Participants Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Inotersen Plasma Clearance At Steady State (CLss/F) At Week 65	3.33 L/hr Standard Deviation 1.21	5.46 L/hr Standard Deviation 5.13

Adverse Events

Inotersen

Serious events: 36 serious events

Other events: 110 other events

Deaths: 5 deaths

Placebo

Serious events: 13 serious events

Other events: 60 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Ionis Pharmaceuticals, Inc.

Phone: 800-679-4747

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Inotersen n=112 participants at risk Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=60 participants at risk Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Infections and infestations Pneumonia	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Bronchitis	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Gastroenteritis	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Urinary tract infection	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Clostridium difficile infection	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Encephalitis	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Herpes zoster	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Peritonitis	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Pyelonephritis acute	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Staphylococcal infection	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Wound infection	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Cellulitis	0.00% 0/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Cardiac failure congestive	3.6% 4/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Cardiac failure	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Cardiac failure acute	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Sinus arrest	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Atrioventricular block	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Bradyarrhythmia	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Pericardial effusion	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Sinus bradycardia	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Abdominal pain	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Constipation	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Gastrointestinal hypomotility	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Haemorrhoids	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Intestinal perforation	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Mesenteric arterial occlusion	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Umbilical hernia	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Vomiting	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Chest pain	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Metabolism and nutrition disorders Dehydration	2.7% 3/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Metabolism and nutrition disorders Cachexia	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Metabolism and nutrition disorders Hyponatraemia	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Nervous system disorders Dementia	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Nervous system disorders Embolic stroke	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Nervous system disorders Haemorrhage intracranial	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.

Other adverse events
Measure	Inotersen n=112 participants at risk Participants received 3 SC doses of 300 mg inotersen during Week 1, followed by once-weekly SC administration for 64 weeks.	Placebo n=60 participants at risk Participants received 3 SC doses of placebo during Week 1, followed by once-weekly SC administration for 64 weeks.
Blood and lymphatic system disorders Anaemia	13.4% 15/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Blood and lymphatic system disorders Thrombocytopenia	12.5% 14/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Cardiac disorders Atrial fibrillation	5.4% 6/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Eye disorders Conjunctival haemorrhage	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	5.0% 3/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Eye disorders Blepharitis	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	6.7% 4/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Abdominal pain	5.4% 6/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	6.7% 4/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Diarrhoea	24.1% 27/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	20.0% 12/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Dry mouth	5.4% 6/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Dysphagia	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	5.0% 3/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Constipation	13.4% 15/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	10.0% 6/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Nausea	31.2% 35/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	11.7% 7/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Gastrointestinal disorders Vomiting	15.2% 17/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Asthenia	12.5% 14/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	13.3% 8/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Chills	17.9% 20/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Fatigue	25.0% 28/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	20.0% 12/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Gait disturbance	5.4% 6/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	8.3% 5/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Injection site bruising	7.1% 8/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Injection site erythema	31.2% 35/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Injection site pain	20.5% 23/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	6.7% 4/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Injection site pruritus	11.6% 13/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Injection site reaction	5.4% 6/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Injection site swelling	5.4% 6/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Influenza like illness	8.0% 9/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Oedema	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	5.0% 3/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Oedema peripheral	18.8% 21/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	10.0% 6/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Pain	1.8% 2/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	8.3% 5/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Pyrexia	19.6% 22/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	8.3% 5/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
General disorders Peripheral swelling	6.2% 7/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Immune system disorders Seasonal allergy	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	6.7% 4/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Urinary tract infection	18.8% 21/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	18.3% 11/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Nasopharyngitis	8.0% 9/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	10.0% 6/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Upper respiratory tract infection	6.2% 7/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	5.0% 3/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Influenza	3.6% 4/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	5.0% 3/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Infections and infestations Rhinitis	0.00% 0/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	6.7% 4/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Injury, poisoning and procedural complications Fall	17.0% 19/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	21.7% 13/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Injury, poisoning and procedural complications Contusion	8.0% 9/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	1.7% 1/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Injury, poisoning and procedural complications Thermal burn	5.4% 6/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	10.0% 6/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Injury, poisoning and procedural complications Ligament sprain	0.89% 1/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	5.0% 3/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Investigations Glomerular filtration rate decreased	5.4% 6/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	3.3% 2/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.
Investigations Platelet count decreased	10.7% 12/112 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.	0.00% 0/60 • Week 1 to Week 91 Adverse events that first occurred or worsened after the first dose of study drug (inotersen or placebo), including serious adverse events, were summarized for each treatment group. Analysis is based on data collected while study treatment was administered and during follow-up until the day of the participant's last contact date within the study. For each treatment, a participant is counted only once within each preferred term.