Trial Outcomes & Findings for SAALT: Subtracting Salt and Adding Losartan Trial (0954A-335) (NCT NCT00739674)

Last Updated: 2024-05-16

Results Overview

Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 14 weeks of treatment

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

992 participants

Primary outcome timeframe

14 Weeks

Results posted on

2024-05-16

Participant Flow

First patient in: FEB-05-2008 Last patient out: JAN-15-2010 Total number of sites: 109 sites in Canada

Participant milestones

Participant milestones
Measure	Losartan-Based Regimen Alone (L Group) Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including hydrochlorothiazide (HCTZ) 12.5 mg or 25 mg and calcium channel blocker (CCB) as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt Dietary Approaches to Stop Hypertension (DASH) diet management.
Overall Study STARTED	535	457
Overall Study Screening Failures	19	17
Overall Study Site 212 Removal	19	13
Overall Study No Follow-up Data	33	18
Overall Study Dietician Consultation >30 Days	1	9
Overall Study Intent-to-treat (ITT) Population	463	400
Overall Study COMPLETED	354	335
Overall Study NOT COMPLETED	181	122

Reasons for withdrawal

Reasons for withdrawal
Measure	Losartan-Based Regimen Alone (L Group) Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including hydrochlorothiazide (HCTZ) 12.5 mg or 25 mg and calcium channel blocker (CCB) as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt Dietary Approaches to Stop Hypertension (DASH) diet management.
Overall Study Screening failures	19	17
Overall Study Site 212 removal	19	13
Overall Study No follow-up data	33	18
Overall Study Dietician consultation >30 days	1	9
Overall Study Adverse Event	22	13
Overall Study Death	1	0
Overall Study Lack of Efficacy	1	0
Overall Study Lost to Follow-up	52	30
Overall Study Protocol Violation	5	5
Overall Study Withdrawal by Subject	9	9
Overall Study Reason missing	2	0
Overall Study Clinic closed	6	4
Overall Study Patient moved	3	2
Overall Study Non compliant	4	0
Overall Study Unable to attend visit	3	1
Overall Study Home monitoring off meds	1	0
Overall Study Erectile dysfunction	0	1

Baseline Characteristics

SAALT: Subtracting Salt and Adding Losartan Trial (0954A-335)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Losartan-Based Regimen Alone (L Group) n=463 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure. The Baseline Measures are reported for the Intent-to-treat (ITT) population (i.e. took at least one dose of the study medication and returned for one follow-up visit).	Diet Management and Losartan-Based Regimen (DML Group) n=400 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management. The Baseline Measures are reported for the Intent-to-treat (ITT) population (i.e. took at least one dose of the study medication and returned for one follow-up visit).	Total n=863 Participants Total of all reporting groups
Age, Continuous	56.05 years STANDARD_DEVIATION 11.54 • n=99 Participants	54.59 years STANDARD_DEVIATION 11.98 • n=107 Participants	55.38 years STANDARD_DEVIATION 11.76 • n=206 Participants
Sex: Female, Male Female	239 Participants n=99 Participants	208 Participants n=107 Participants	447 Participants n=206 Participants
Sex: Female, Male Male	224 Participants n=99 Participants	192 Participants n=107 Participants	416 Participants n=206 Participants
Race/Ethnicity, Customized White	404 participants n=99 Participants	369 participants n=107 Participants	773 participants n=206 Participants
Race/Ethnicity, Customized Black	9 participants n=99 Participants	4 participants n=107 Participants	13 participants n=206 Participants
Race/Ethnicity, Customized Hispanic	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Race/Ethnicity, Customized Asian	38 participants n=99 Participants	20 participants n=107 Participants	58 participants n=206 Participants
Race/Ethnicity, Customized Native Indian	3 participants n=99 Participants	2 participants n=107 Participants	5 participants n=206 Participants
Race/Ethnicity, Customized Other	7 participants n=99 Participants	4 participants n=107 Participants	11 participants n=206 Participants
Cardiovascular Risk High	112 Participants n=99 Participants	92 Participants n=107 Participants	204 Participants n=206 Participants
Cardiovascular Risk Medium	94 Participants n=99 Participants	61 Participants n=107 Participants	155 Participants n=206 Participants
Cardiovascular Risk Low	218 Participants n=99 Participants	216 Participants n=107 Participants	434 Participants n=206 Participants
Cardiovascular Risk Not Available	35 Participants n=99 Participants	27 Participants n=107 Participants	62 Participants n=206 Participants
Cardiovascular Risk Missing	4 Participants n=99 Participants	4 Participants n=107 Participants	8 Participants n=206 Participants
Diastolic Blood Pressure	90.67 mm Hg STANDARD_DEVIATION 9.19 • n=99 Participants	91.43 mm Hg STANDARD_DEVIATION 9.98 • n=107 Participants	91.02 mm Hg STANDARD_DEVIATION 9.57 • n=206 Participants
Systolic Blood Pressure	151.23 mm Hg STANDARD_DEVIATION 10.80 • n=99 Participants	151.11 mm Hg STANDARD_DEVIATION 12.55 • n=107 Participants	151.17 mm Hg STANDARD_DEVIATION 11.64 • n=206 Participants
Weight	85.41 Kilograms STANDARD_DEVIATION 19.95 • n=99 Participants	89.17 Kilograms STANDARD_DEVIATION 20.18 • n=107 Participants	87.16 Kilograms STANDARD_DEVIATION 20.13 • n=206 Participants

PRIMARY outcome

Timeframe: 14 Weeks

Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 392 and 357 patients at week 14 for L group and DML group respectively.

Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 14 weeks of treatment

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=392 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=357 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline Achieve Target Blood Pressure	276 Participants	270 Participants
Number of Patients Achieving Target Blood Pressure at Week 14 From Baseline Did not Achieve Target Blood Pressure	116 Participants	87 Participants

PRIMARY outcome

Timeframe: 14 Weeks

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=392 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=357 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Change in Systolic Blood Pressure From Baseline to Week 14	-21.01 mm Hg Standard Deviation 14.11	-22.74 mm Hg Standard Deviation 15.81

PRIMARY outcome

Timeframe: 14 Weeks

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=392 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=357 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Change in Diastolic Blood Pressure From Baseline to Week 14	-10.19 mm Hg Standard Deviation 9.33	-12.05 mm Hg Standard Deviation 9.50

SECONDARY outcome

Timeframe: 6 Weeks

Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 431 and 383 patients at week 6 for L group and DML group respectively.

Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 6 weeks of treatment

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=431 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=383 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline Achieve Target Blood Pressure	239 Participants	231 Participants
Number of Patients Achieving Target Blood Pressure at Week 6 From Baseline Did not Achieve Target Blood Pressure	192 Participants	152 Participants

SECONDARY outcome

Timeframe: 10 Weeks

Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 399 and 370 patients at week 10 for L group and DML group respectively.

Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 10 weeks of treatment

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=399 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=370 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline Achieve Target Blood Pressure	257 Participants	254 Participants
Number of Patients Achieving Target Blood Pressure at Week 10 From Baseline Did not Achieve Target Blood Pressure	142 Participants	116 Participants

SECONDARY outcome

Timeframe: 40 Weeks

Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 351 and 331 patients at week 40 for L group and DML group respectively.

Number of Patients Achieving Target Blood Pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics) from baseline after 40 weeks of treatment

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=351 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=331 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline Did not Achieve Target Blood Pressure	87 Participants	91 Participants
Number of Patients Achieving Target Blood Pressure at Week 40 From Baseline Achieve Target Blood Pressure	264 Participants	240 Participants

SECONDARY outcome

Timeframe: 6 Weeks

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=431 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=383 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Change in Systolic Blood Pressure From Baseline to Week 6	-16.81 mm Hg Standard Deviation 14.92	-18.85 mm Hg Standard Deviation 16.18

SECONDARY outcome

Timeframe: 6 Weeks

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=431 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=383 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Change in Diastolic Blood Pressure From Baseline to Week 6	-8.34 mm Hg Standard Deviation 9.29	-9.76 mm Hg Standard Deviation 9.82

SECONDARY outcome

Timeframe: 10 Weeks

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=399 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=370 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Change in Systolic Blood Pressure From Baseline to Week 10	-19.11 mm Hg Standard Deviation 14.87	-20.95 mm Hg Standard Deviation 16.24

SECONDARY outcome

Timeframe: 10 Weeks

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=399 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=370 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Change in Diastolic Blood Pressure From Baseline to Week 10	-9.48 mm Hg Standard Deviation 8.80	-11.42 mm Hg Standard Deviation 9.45

SECONDARY outcome

Timeframe: 14 Weeks

Population: 463 and 400 - number of patients that received at least one dose of study medication and had 1 follow-up visit (ITT population). Information available for 437 and 386 patients for L group and DML group respectively.

Time to achieve the target blood pressure (\<140/90 mm Hg and \<130/80 mm Hg for diabetics).

Outcome measures

Outcome measures
Measure	Losartan-Based Regimen Alone (L Group) n=437 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=386 Participants Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Time to Achieve the Target Blood Pressure From Baseline	7.43 Weeks Interval 6.24 to 8.62	6.57 Weeks Interval 6.29 to 6.85

Adverse Events

Losartan-Based Regimen Alone (L Group)

Serious events: 13 serious events

Other events: 55 other events

Deaths: 0 deaths

Diet Management and Losartan-Based Regimen (DML Group)

Serious events: 10 serious events

Other events: 46 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Results disclosure agreements

Principal investigator is a sponsor employee Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Losartan-Based Regimen Alone (L Group) n=531 participants at risk Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=453 participants at risk Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Cardiac disorders Acute myocardial infarction	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.44% 2/453 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Atrial fibrillation	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Cardiac failure congestive	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Cardio-respiratory arrest	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Myocardial infarction	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.44% 2/453 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Palpitations	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Supraventricular tachycardia	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Tachycardia	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Dry mouth	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Oesophagitis	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Pancreatitis acute	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Inflammation	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Injury, poisoning and procedural complications Pseudocyst	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Immune system disorders Amyloidosis	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Appendicitis	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Diverticulitis	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Gastroenteritis	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Pneumonia	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Investigations Blood creatine phosphokinase increased	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Investigations Red blood cell sedimentation rate increased	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bladder	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Nervous system disorders Haemorrhagic stroke	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Nervous system disorders Transient ischaemic attack	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Renal and urinary disorders Nephrolithiasis	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	— 0/0 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Renal and urinary disorders Renal failure acute	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Reproductive system and breast disorders Epididymitis	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Vascular disorders Hypertension	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Vascular disorders Hypotension	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.

Other adverse events
Measure	Losartan-Based Regimen Alone (L Group) n=531 participants at risk Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure.	Diet Management and Losartan-Based Regimen (DML Group) n=453 participants at risk Losartan-based regimen (50 mg or 100 mg once daily for 40 weeks) with sequential titration including HCTZ 12.5 mg or 25 mg and CCB as needed to achieve target blood pressure combined with low-salt DASH diet management.
Investigations Heart rate increased	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Lower respiratory tract infection	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Nail infection	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Nasopharyngitis	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Sinusitis	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.44% 2/453 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Infections and infestations Upper respiratory tract infection	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.66% 3/453 • Number of events 3 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Injury, poisoning and procedural complications Drug exposure during pregnancy	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Injury, poisoning and procedural complications Fall	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Injury, poisoning and procedural complications Incorrect dose administered	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Injury, poisoning and procedural complications Wrong technique in drug usage process	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Investigations Blood pressure decreased	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.44% 2/453 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Investigations Blood pressure increased	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Investigations C-reactive protein abnormal	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Investigations Creatinine urine increased	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Arrhythmia	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Cardiac disorders Palpitations	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Eye disorders Eye irritation	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Eye disorders Vision blurred	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Abdominal distension	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Abdominal mass	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Abdominal pain	0.38% 2/531 • Number of events 3 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Abdominal pain upper	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Anal fissure	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Diarrhoea	0.56% 3/531 • Number of events 5 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.44% 2/453 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Dry mouth	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Nausea	0.38% 2/531 • Number of events 3 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.66% 3/453 • Number of events 3 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Toothache	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Gastrointestinal disorders Vomiting	0.00% 0/531 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Asthenia	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Chest discomfort	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Chest pain	0.38% 2/531 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Discomfort	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Drug ineffective	0.38% 2/531 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Fatigue	0.75% 4/531 • Number of events 4 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.44% 2/453 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Malaise	0.19% 1/531 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Oedema	0.19% 1/531 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
General disorders Oedema peripheral	0.38% 2/531 • Number of events 2 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.22% 1/453 • Number of events 1 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.
Immune system disorders Drug hypersensitivity	0.56% 3/531 • Number of events 3 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.	0.00% 0/453 A total of 8 patients were removed from the safety population because they did not receive at least one dose of the study medication. Therefore, the safety population was based on 984 patients (531 in the L Group and 453 in the DML Group) of the total 992 enrolled patients.