Trial Outcomes & Findings for ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC) (NCT NCT02319005)

NCT ID: NCT02319005

Last Updated: 2018-07-18

Results Overview

The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

206 participants

Primary outcome timeframe

18 months

Results posted on

2018-07-18

Participant Flow

A total of 206 patients with hereditary amyloid transthyretin (hATTR) cardiac amyloidosis were enrolled and randomized in the study.

Participant milestones

Participant milestones
Measure	Revusiran (ALN-TTRSC) All patients who received at least 1 dose of revusiran	Placebo All patients who received at least 1 dose of placebo
Overall Study STARTED	140	66
Overall Study COMPLETED	92	51
Overall Study NOT COMPLETED	48	15

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Revusiran n=140 Participants All patients who received at least 1 dose of revusiran	Placebo n=66 Participants All patients who received at least 1 dose of placebo	Total n=206 Participants Total of all reporting groups
Age, Continuous	68.6 years STANDARD_DEVIATION 9.28 • n=5 Participants	66.2 years STANDARD_DEVIATION 9.52 • n=7 Participants	67.8 years STANDARD_DEVIATION 9.40 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	13 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	105 Participants n=5 Participants	53 Participants n=7 Participants	158 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	129 Participants n=5 Participants	65 Participants n=7 Participants	194 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	68 Participants n=5 Participants	36 Participants n=7 Participants	104 Participants n=5 Participants
Race (NIH/OMB) White	66 Participants n=5 Participants	29 Participants n=7 Participants	95 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	0 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: Study drug was discontinued early due to an imbalance in mortality observed between patients treated with revusiran and placebo. No patients had an 18-month visit, therefore, the endpoints cannot be calculated as data were not collected.

The difference between revusiran and placebo group in change from baseline to 18 months in the total distance walked in 6 minutes

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 18 months

The difference between revusiran (ALN-TTRSC) and placebo group in the percent reduction in serum TTR levels over 18 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

Number of cardiovascular-related deaths and cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

The difference between revusiran (ALN-TTRSC) and placebo group in the change from baseline to 18 months in the NYHA class

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

The difference between revusiran (ALN-TTRSC) and placebo group in the change from Baseline to 18 months in the Kansas City Cardiomyopathy Questionnaire

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

Number of cardiovascular-related deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

Number of cardiovascular-related hospitalizations in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 months

Total number of deaths in the placebo group compared to the revusiran (ALN-TTRSC) treatment group

Outcome measures

Outcome data not reported

Adverse Events

Revusiran

Serious events: 83 serious events

Other events: 136 other events

Deaths: 23 deaths

Placebo

Serious events: 34 serious events

Other events: 62 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Alnylam Pharmaceuticals Inc

Phone: 866-330-0326

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Revusiran n=140 participants at risk All patients who received at least 1 dose of revusiran	Placebo n=66 participants at risk All patients who received at least 1 dose of placebo
Metabolism and nutrition disorders Hyperkalaemia	0.71% 1/140 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiac failure	17.9% 25/140 • Number of events 35 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	13.6% 9/66 • Number of events 13 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiac failure acute	10.7% 15/140 • Number of events 20 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	13.6% 9/66 • Number of events 12 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiac failure congestive	6.4% 9/140 • Number of events 12 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 6 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Atrial fibrillation	5.0% 7/140 • Number of events 8 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Renal and urinary disorders Renal failure acute	3.6% 5/140 • Number of events 7 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Neuropathy peripheral	5.0% 7/140 • Number of events 7 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Syncope	2.9% 4/140 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	4.5% 3/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Atrial flutter	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Dehydration	2.1% 3/140 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	4.5% 3/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiac failure chronic	2.9% 4/140 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Vascular disorders Hypotension	2.1% 3/140 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Renal and urinary disorders Renal failure	2.1% 3/140 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Malnutrition	2.9% 4/140 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiac arrest	2.1% 3/140 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Impaired gastric emptying	4.3% 6/140 • Number of events 6 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Hyponatraemia	1.4% 2/140 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Failure to thrive	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Renal and urinary disorders Urinary retention	0.71% 1/140 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Diarrhoea	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Hypokalaemia	0.71% 1/140 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Infections and infestations Pneumonia	2.1% 3/140 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Vomiting	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Presyncope	0.00% 0/140 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.71% 1/140 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Ventricular tachycardia	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Cachexia	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
General disorders Death	0.71% 1/140 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Subarachnoid hemorrhage	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Musculoskeletal and connective tissue disorders Osteoarthritis	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Infections and infestations Sepsis	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
General disorders Asthenia	0.71% 1/140 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Investigations Weight decreased	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Atrioventricular block complete	0.71% 1/140 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Cerebrovascular accident	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Convulsion	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Investigations Liver function test abnormal	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiogenic shock	1.4% 2/140 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiac amyloidosis	0.71% 1/140 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study

Other adverse events
Measure	Revusiran n=140 participants at risk All patients who received at least 1 dose of revusiran	Placebo n=66 participants at risk All patients who received at least 1 dose of placebo
General disorders Injection Site Pain	16.4% 23/140 • Number of events 101 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 13 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
General disorders Injection site erythema	11.4% 16/140 • Number of events 64 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	0.00% 0/66 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
General disorders Fatigue	10.0% 14/140 • Number of events 16 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	12.1% 8/66 • Number of events 32 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiac failure	7.1% 10/140 • Number of events 14 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	4.5% 3/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Respiratory, thoracic and mediastinal disorders Cough	17.9% 25/140 • Number of events 29 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	15.2% 10/66 • Number of events 14 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Constipation	14.3% 20/140 • Number of events 23 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	16.7% 11/66 • Number of events 13 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Nausea	14.3% 20/140 • Number of events 28 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	7.6% 5/66 • Number of events 7 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Dizziness	12.9% 18/140 • Number of events 19 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	19.7% 13/66 • Number of events 15 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 14/140 • Number of events 19 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	12.1% 8/66 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Neuropathy peripheral	14.3% 20/140 • Number of events 21 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	9.1% 6/66 • Number of events 6 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.4% 16/140 • Number of events 22 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	13.6% 9/66 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Nervous system disorders Hypoaesthesia	8.6% 12/140 • Number of events 21 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 5 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Vomiting	6.4% 9/140 • Number of events 18 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	7.6% 5/66 • Number of events 7 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Injury, poisoning and procedural complications Fall	7.1% 10/140 • Number of events 16 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	7.6% 5/66 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Atrial fibrillation	11.4% 16/140 • Number of events 20 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Hypokalaemia	4.3% 6/140 • Number of events 10 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	12.1% 8/66 • Number of events 12 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Decreased appetite	9.3% 13/140 • Number of events 16 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	9.1% 6/66 • Number of events 6 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Vascular disorders Hypotension	7.9% 11/140 • Number of events 15 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Gout	2.1% 3/140 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	10.6% 7/66 • Number of events 16 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
General disorders Asthenia	10.7% 15/140 • Number of events 18 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Investigations Weight decreased	8.6% 12/140 • Number of events 14 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 5 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Investigations Blood lactic acid increased	10.7% 15/140 • Number of events 16 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	4.5% 3/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Musculoskeletal and connective tissue disorders Arthralgia	6.4% 9/140 • Number of events 10 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	9.1% 6/66 • Number of events 8 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Infections and infestations Nasopharyngitis	7.9% 11/140 • Number of events 11 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	7.6% 5/66 • Number of events 5 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Investigations Blood bilirubin increased	7.1% 10/140 • Number of events 11 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Abdominal pain	5.0% 7/140 • Number of events 10 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	4.5% 3/66 • Number of events 5 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Diarrhoea	6.4% 9/140 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	7.6% 5/66 • Number of events 5 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Infections and infestations Bronchitis	7.1% 10/140 • Number of events 11 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	4.5% 3/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Musculoskeletal and connective tissue disorders Muscle spasms	6.4% 9/140 • Number of events 11 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Investigations Liver function test abnormal	8.6% 12/140 • Number of events 12 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Cardiac disorders Cardiac failure congestive	2.9% 4/140 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	9.1% 6/66 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Infections and infestations Sinusitis	5.0% 7/140 • Number of events 8 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	4.5% 3/66 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Infections and infestations Upper respiratory tract infection	5.7% 8/140 • Number of events 8 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 4 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Renal and urinary disorders Renal failure acute	6.4% 9/140 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 3 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Metabolism and nutrition disorders Fluid overload	4.3% 6/140 • Number of events 6 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	6.1% 4/66 • Number of events 6 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Skin and subcutaneous tissue disorders Pruritus	6.4% 9/140 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Respiratory, thoracic and mediastinal disorders Productive cough	6.4% 9/140 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Psychiatric disorders Insomnia	5.7% 8/140 • Number of events 8 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	3.0% 2/66 • Number of events 2 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study
Gastrointestinal disorders Abdominal pain upper	6.4% 9/140 • Number of events 9 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study	1.5% 1/66 • Number of events 1 • All adverse events (AEs) that occurred after the start of study drug administration on Day 0 (Baseline) up to 90 days post modified early termination visit (End of Study); Median duration of collection was 10 months The same event may appear as both an AE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study