Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo for Relief of Heartburn in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (NERD) (NCT NCT05195528)

NCT ID: NCT05195528

Last Updated: 2023-12-29

Results Overview

Participants were assigned an electronic diary to complete twice daily, in the morning and evening. Diary day was considered heartburn-free if both morning and evening diary entries were heartburn-free and there was no reported use of rescue antacid, H2RAs, or PPIs.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 776 participants
• Primary outcome timeframe: Day 1 to Day 28
• Results posted on: 2023-12-29

Participant Flow

Participants were recruited across 91 sites in the United States in the period of time from January 2022 to May 2023. Participants were in the study for a period of time up to 33 weeks.

Participant were randomized in a 1:1:1 ratio to receive vonoprazan 10 mg , vonoprazan 20 mg, or placebo during the Part 1 Placebo-controlled Treatment Period. In the Part 2 Extension Period participants who had been assigned vonoprazan in Part 1 continued with their assigned treatment while those assigned placebo in Part 1 were re-randomized to receive vonoprazan 10 mg or 20 mg.

Participant milestones

Measure	Placebo Participants with Non-Erosive Gastroesophageal Reflux Disease (NERD) and heartburn symptoms were randomized to receive placebo once per day (QD) for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 10 mg Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 10 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period. Participants could continue taking vonoprazan 10 mg for an additional 20 weeks in the Part 2 Extension Period.	Vonoprazan 20 mg Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 20 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period. Participants continued taking vonoprazan 20 mg for an additional 20 weeks in the Part 2 Extension Period.	Placebo/Vonoprazan 10 mg Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 10 mg for 20 weeks in the Part 2 Extension Period.	Placebo/Vonoprazan 20 mg Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 20 mg for 20 weeks in the Part 2 Extension Period.
Placebo-controlled Treatment Period STARTED	259	258	259	0	0
Placebo-controlled Treatment Period Intent to Treat Analysis Set	258	257	257	0	0
Placebo-controlled Treatment Period Safety Analysis Set	256	259	257	0	0
Placebo-controlled Treatment Period COMPLETED	247	250	242	0	0
Placebo-controlled Treatment Period NOT COMPLETED	12	8	17	0	0
Extension Period STARTED	0	247	237	122	122
Extension Period Intent to Treat Analysis Set	0	247	235	119	122
Extension Period Safety Analysis Set	0	248	236	118	121
Extension Period COMPLETED	0	219	206	106	103
Extension Period NOT COMPLETED	0	28	31	16	19

Reasons for withdrawal

Measure	Placebo Participants with Non-Erosive Gastroesophageal Reflux Disease (NERD) and heartburn symptoms were randomized to receive placebo once per day (QD) for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 10 mg Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 10 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period. Participants could continue taking vonoprazan 10 mg for an additional 20 weeks in the Part 2 Extension Period.	Vonoprazan 20 mg Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 20 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period. Participants continued taking vonoprazan 20 mg for an additional 20 weeks in the Part 2 Extension Period.	Placebo/Vonoprazan 10 mg Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 10 mg for 20 weeks in the Part 2 Extension Period.	Placebo/Vonoprazan 20 mg Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 20 mg for 20 weeks in the Part 2 Extension Period.
Placebo-controlled Treatment Period Protocol Violation	1	1	0	0	0
Placebo-controlled Treatment Period Pre-Treatment Event (PTE) or Adverse Event (AE) or Serious Adverse Event (SAE)	2	1	6	0	0
Placebo-controlled Treatment Period Lost to Follow-up	0	3	4	0	0
Placebo-controlled Treatment Period Withdrawal by Subject	6	2	4	0	0
Placebo-controlled Treatment Period Lack of Efficacy	2	0	0	0	0
Placebo-controlled Treatment Period Not Treated	1	1	2	0	0
Placebo-controlled Treatment Period Other	0	0	1	0	0
Extension Period PTE or AE or SAE	0	4	5	4	4
Extension Period Protocol Violation	0	2	1	0	1
Extension Period Lost to Follow-up	0	6	13	3	7
Extension Period Withdrawal by Subject	0	12	9	6	5
Extension Period Lack of Efficacy	0	3	0	0	2
Extension Period Not Treated	0	0	2	3	0
Extension Period Other	0	1	1	0	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Vonoprazan Compared to Placebo for Relief of Heartburn in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease (NERD)

Baseline characteristics by cohort

Measure	Placebo n=258 Participants Participants with NERD and heartburn symptoms were randomized to receive placebo QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 10 mg n=257 Participants Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 10 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 20 mg n=257 Participants Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 20 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Total n=772 Participants Total of all reporting groups
Age, Continuous	51.5 Years STANDARD_DEVIATION 14.74 • n=93 Participants	51 Years STANDARD_DEVIATION 14.03 • n=4 Participants	50.4 Years STANDARD_DEVIATION 14.39 • n=27 Participants	50.9 Years STANDARD_DEVIATION 14.38 • n=483 Participants
Sex: Female, Male Female	179 Participants n=93 Participants	182 Participants n=4 Participants	166 Participants n=27 Participants	527 Participants n=483 Participants
Sex: Female, Male Male	79 Participants n=93 Participants	75 Participants n=4 Participants	91 Participants n=27 Participants	245 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	77 Participants n=93 Participants	87 Participants n=4 Participants	80 Participants n=27 Participants	244 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	180 Participants n=93 Participants	165 Participants n=4 Participants	171 Participants n=27 Participants	516 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants	12 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	3 Participants n=4 Participants	0 Participants n=27 Participants	4 Participants n=483 Participants
Race (NIH/OMB) Asian	12 Participants n=93 Participants	22 Participants n=4 Participants	11 Participants n=27 Participants	45 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	33 Participants n=93 Participants	38 Participants n=4 Participants	52 Participants n=27 Participants	123 Participants n=483 Participants
Race (NIH/OMB) White	205 Participants n=93 Participants	186 Participants n=4 Participants	185 Participants n=27 Participants	576 Participants n=483 Participants
Race (NIH/OMB) More than one race	3 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants	11 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	13 Participants n=483 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 28

Population: Intent-to-treat (ITT) was defined as all participants randomized into the placebo-controlled treatment period who received at least one dose of study drug and had available data.

Participants were assigned an electronic diary to complete twice daily, in the morning and evening. Diary day was considered heartburn-free if both morning and evening diary entries were heartburn-free and there was no reported use of rescue antacid, H2RAs, or PPIs.

Outcome measures

Measure	Placebo n=256 Participants Participants with NERD and heartburn symptoms were randomized to receive placebo QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 10 mg n=256 Participants Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 10 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 20 mg n=257 Participants Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 20 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.
Percentage of Days Without Daytime or Nighttime Heartburn	27.7 Percentage of days Interval 23.92 to 31.46	44.8 Percentage of days Interval 41.06 to 48.58	44.4 Percentage of days Interval 40.62 to 48.15

SECONDARY outcome

Timeframe: Day 1 to Day 28

Population: ITT was defined as all participants randomized into the placebo-controlled treatment period who received at least one dose of study drug and had available data.

Participants were assigned an electronic diary to complete twice daily, in the morning and evening. Participants recorded use of rescue antacid.

Outcome measures

Measure	Placebo n=256 Participants Participants with NERD and heartburn symptoms were randomized to receive placebo QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 10 mg n=254 Participants Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 10 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 20 mg n=257 Participants Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 20 mg QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.
Percentage of Days Without Rescue Antacid Use	47.6 Percentage of days Interval 43.43 to 51.68	63.3 Percentage of days Interval 59.19 to 67.45	61.2 Percentage of days Interval 57.12 to 65.36

Adverse Events

Placebo (Part 1: 4 Weeks)

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Vonoprazan 10 mg (Part 1: 4 Weeks)

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Vonoprazan 20 mg (Part 1: 4 Weeks) Part 1

Serious events: 2 serious events

Other events: 32 other events

Deaths: 0 deaths

Placebo/Vonoprazan 10 mg (Part 2: 20 Weeks)

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo/Vonoprazan 20 mg (Part 2: 20 Weeks)

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Vonoprazan 10 mg/Vonoprazan 10 mg (Part 2: 20 Weeks)

Serious events: 7 serious events

Other events: 40 other events

Deaths: 0 deaths

Vonoprazan 20/Vonoprazan 20 mg (Part 2: 20 Weeks)

Serious events: 3 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo (Part 1: 4 Weeks) n=256 participants at risk Participants with NERD and heartburn symptoms were randomized to receive placebo QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 10 mg (Part 1: 4 Weeks) n=259 participants at risk Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 10 mg QD for 4 weeks during the Part 1 Placebo-controlled Treament Period.	Vonoprazan 20 mg (Part 1: 4 Weeks) Part 1 n=257 participants at risk Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 20 mg QD for 4 weeks during the Part 1 Placebo-controlled Treament Period.	Placebo/Vonoprazan 10 mg (Part 2: 20 Weeks) n=118 participants at risk Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 10 mg for 20 weeks in the Part 2 Extension Period.	Placebo/Vonoprazan 20 mg (Part 2: 20 Weeks) n=121 participants at risk Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 20 mg for 20 weeks in the Part 2 Extension Period.	Vonoprazan 10 mg/Vonoprazan 10 mg (Part 2: 20 Weeks) n=248 participants at risk Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 10 mg for 20 weeks in the Part 2 Extension Period.	Vonoprazan 20/Vonoprazan 20 mg (Part 2: 20 Weeks) n=236 participants at risk Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 20 mg for 20 weeks in the Part 2 Extension Period.
Gastrointestinal disorders Salivary gland calculus	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.39% 1/257 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Infections and infestations Viral pericarditis	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.39% 1/259 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.39% 1/257 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.39% 1/257 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.83% 1/121 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.81% 2/248 • Number of events 2 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.42% 1/236 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.83% 1/121 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.42% 1/236 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
General disorders Non-cardiac chest pain	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.83% 1/121 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Cardiac disorders Angina pectoris	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.85% 1/118 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Ear and labyrinth disorders Vertigo	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.40% 1/248 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.42% 1/236 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Nervous system disorders Cerebrovascular accident	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.85% 1/118 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Psychiatric disorders Bipolar disorder	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.83% 1/121 • Number of events 1 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.

Other adverse events

Measure	Placebo (Part 1: 4 Weeks) n=256 participants at risk Participants with NERD and heartburn symptoms were randomized to receive placebo QD for 4 weeks during the Part 1 Placebo-controlled Treatment Period.	Vonoprazan 10 mg (Part 1: 4 Weeks) n=259 participants at risk Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 10 mg QD for 4 weeks during the Part 1 Placebo-controlled Treament Period.	Vonoprazan 20 mg (Part 1: 4 Weeks) Part 1 n=257 participants at risk Participants with NERD and heartburn symptoms were randomized to receive vonoprazan 20 mg QD for 4 weeks during the Part 1 Placebo-controlled Treament Period.	Placebo/Vonoprazan 10 mg (Part 2: 20 Weeks) n=118 participants at risk Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 10 mg for 20 weeks in the Part 2 Extension Period.	Placebo/Vonoprazan 20 mg (Part 2: 20 Weeks) n=121 participants at risk Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 20 mg for 20 weeks in the Part 2 Extension Period.	Vonoprazan 10 mg/Vonoprazan 10 mg (Part 2: 20 Weeks) n=248 participants at risk Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 10 mg for 20 weeks in the Part 2 Extension Period.	Vonoprazan 20/Vonoprazan 20 mg (Part 2: 20 Weeks) n=236 participants at risk Participants randomized to placebo during the Part 1 Placebo-controlled Treatment Period were re-randomized to receive vonoprazan 20 mg for 20 weeks in the Part 2 Extension Period.
Gastrointestinal disorders Abdominal pain	0.78% 2/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.5% 4/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.3% 6/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.83% 1/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.40% 1/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.3% 3/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.78% 2/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.3% 6/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.78% 2/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.85% 1/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.2% 3/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.42% 1/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	1.2% 3/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.3% 6/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.39% 1/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.2% 3/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.85% 2/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.39% 1/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.3% 6/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	3.1% 8/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.85% 1/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.83% 1/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.2% 3/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.1% 5/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Infections and infestations COVID-19	0.78% 2/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.2% 3/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.6% 4/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	10.2% 12/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.5% 3/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	4.4% 11/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	8.5% 20/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Infections and infestations Gastroenteritis	0.39% 1/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.83% 1/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.40% 1/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.1% 5/236 • Number of events 5 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Infections and infestations Influenza	0.39% 1/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.39% 1/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	3.4% 4/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.0% 5/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.3% 3/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	1.2% 3/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.39% 1/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.9% 5/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.1% 5/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Infections and infestations Sinusitis	0.00% 0/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.77% 2/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.39% 1/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	3.2% 8/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.3% 3/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.39% 1/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.78% 2/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.83% 1/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	4.8% 12/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.1% 5/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.
Infections and infestations Urinary tract infection	1.2% 3/256 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.5% 4/259 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.6% 4/257 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	1.7% 2/118 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	0.00% 0/121 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.0% 5/248 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.	2.5% 6/236 • All-cause mortality was collected from time of enrollment through 33 weeks (5 weeks screening, 4 weeks Placebo-controlled Treatment Period, 20 weeks Extension Period, 4 weeks follow-up). Treatment-emergent adverse events were collected from first dose of study treatment through 28 weeks. All-cause mortality was summarized for all enrolled participants. Serious and Other Adverse Events were summarized in the SAS, which includes randomized subjects who received at least one dose of study drug.

Additional Information

Phathom Medical Information

Phathom Pharmaceuticals, Inc.

Phone: 1-888-775-7428

Email: medicalinformation@phathompharma.com

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