parallel randomized trial

NCT06250946

A Multicenter, Randomized, Double-blinded, Placebo-controlled, Parallel-group Phase ⅡStudy to Evaluate the Efficacy and Safety of HRS-7535 in Obese Subjects

Overweight or obesity without diabetes (adults)NCT06250946S002275

Design

Randomized: 235
Start year: 2024
Treatment: 36 weeks, follow-up 38 weeks
Countries: China (29 sites)
Sponsor: Shandong Suncadia Medicine Co., Ltd. (industry)
Eligibility: age 18 to 65; BMI 28 to 40; no diabetes, HbA1c below 6.5 percent

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: randomized
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Placebo Placebo	lifestyle: standard	46	46	43
A2	HRS-7535 30 mg tablet once daily HRS-7535 30 mg	lifestyle: standard	48	48	38
A3	HRS-7535 60 mg tablet once daily HRS-7535 60 mg	lifestyle: standard	47	47	42
A4	HRS-7535 120 mg tablet once daily HRS-7535 120 mg	lifestyle: standard	46	46	41
A5	HRS-7535 180 mg tablet once daily HRS-7535 180 mg	lifestyle: standard	48	48	40

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Placebo A1	HRS-7535 30 mg tablet once daily A2	HRS-7535 60 mg tablet once daily A3	HRS-7535 120 mg tablet once daily A4	HRS-7535 180 mg tablet once daily A5
age	mean (years)	35.1	34.1	31.5	33.2	33.5
age	sd (years)	8.2	8.3	7.3	6.6	10.2
bmi: 32.5 or more	n	20	20	22	20	21
bmi: 32.5 or more	percent	43.5	41.7	46.8	43.5	43.8
bmi: less than 32.5	n	26	28	25	26	27
bmi: less than 32.5	percent	56.5	58.3	53.2	56.5	56.3
bmi	mean (kg/m2)	32.4	32.7	32.8	32.3	32.3
bmi	sd (kg/m2)	2.6	3.4	3.2	3.2	2.5
egfr	mean (mL/min/1.73 m2)	112.1	110.7	112.9	112.0	113.5
egfr	sd (mL/min/1.73 m2)	13.3	13.2	13.8	14.0	14.9
female	n	22	23	23	22	24
female	percent	47.8	47.9	48.9	47.8	50.0
hba1c	mean (percent)	5.3	5.3	5.2	5.3	5.3
hba1c	sd (percent)	0.3	0.3	0.3	0.3	0.3
sbp	mean (mmHg)	120.5	118.9	118.3	119.5	118.3
sbp	sd (mmHg)	12.3	11.2	10.8	11.6	11.3
waist	mean (cm)	104.3	103.9	104.9	103.2	103.7
waist	sd (cm)	9.5	10.8	9.5	9.6	8.5
weight	mean (kg)	90.4	91.7	93.9	90.2	91.7
weight	sd (kg)	13.1	14.6	13.9	13.7	14.3

Analyses this trial contributes to

Results

207 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

Systolic blood pressure change (18 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Detail
26	A1	change	-3.25 mmHg	-5.72 to -0.78	hypothetical; randomized; R0001289:Supplement Table 4
26	A2	change	-4.09 mmHg	-6.68 to -1.51	hypothetical; randomized; R0001289:Supplement Table 4
26	A2 vs A1	md	-0.85 mmHg	-4.42 to 2.73	hypothetical; randomized; R0001289:Supplement Table 4
26	A3 vs A1	md	-1.34 mmHg	-4.85 to 2.17	hypothetical; randomized; R0001289:Supplement Table 4
26	A3	change	-4.59 mmHg	-7.08 to -2.10	hypothetical; randomized; R0001289:Supplement Table 4
26	A4	change	-5.84 mmHg	-8.35 to -3.33	hypothetical; randomized; R0001289:Supplement Table 4
26	A4 vs A1	md	-2.59 mmHg	-6.11 to 0.93	hypothetical; randomized; R0001289:Supplement Table 4
26	A5	change	-5.86 mmHg	-8.38 to -3.35	hypothetical; randomized; R0001289:Supplement Table 4
26	A5 vs A1	md	-2.61 mmHg	-6.14 to 0.91	hypothetical; randomized; R0001289:Supplement Table 4
36	A1	change	-1.28 mmHg	-3.83 to 1.26	hypothetical; randomized; R0001289:Supplement Table 4
36	A2	change	-3.27 mmHg	-5.95 to -0.60	hypothetical; randomized; R0001289:Supplement Table 4
36	A2 vs A1	md	-1.99 mmHg	-5.68 to 1.70	hypothetical; randomized; R0001289:Supplement Table 4
36	A3	change	-3.75 mmHg	-6.31 to -1.19	hypothetical; randomized; R0001289:Supplement Table 4
36	A3 vs A1	md	-2.47 mmHg	-6.08 to 1.14	hypothetical; randomized; R0001289:Supplement Table 4
36	A4	change	-3.92 mmHg	-6.50 to -1.33	hypothetical; randomized; R0001289:Supplement Table 4
36	A4 vs A1	md	-2.63 mmHg	-6.25 to 0.99	hypothetical; randomized; R0001289:Supplement Table 4
36	A5	change	-0.72 mmHg	-3.31 to 1.88	hypothetical; randomized; R0001289:Supplement Table 4
36	A5 vs A1	md	0.57 mmHg	-3.07 to 4.20	hypothetical; randomized; R0001289:Supplement Table 4

Percent body weight change (72 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	percent change	-2.50 percent	-4.35 to -0.66		hypothetical; randomized; R0001289:Supplement Table S1
26	A1	percent change	-3.44 percent	-6.02 to -0.87	24	hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table 2
26	A1	percent change	-1.26 percent	-3.96 to 1.44	19	hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table 2
26	A1	percent change	-2.50 percent	-4.34 to -0.65		hypothetical; randomized; R0001289:Table 2
26	A1	percent change	-2.48 percent	-4.65 to -0.31	23	hypothetical; randomized; sex:male; R0001289:Supplement Table 2
26	A1	percent change	-2.37 percent	-5.37 to 0.64	20	hypothetical; randomized; sex:female; R0001289:Supplement Table 2
26	A1	percent change	-2.54 percent	-4.39 to -0.70	46	treatment policy; randomized; R0001289:Supplement Table S1
26	A2	percent change	-2.99 percent	-4.84 to -1.14		hypothetical; randomized; R0001289:Table 2
26	A2	percent change	-1.78 percent	-4.56 to 0.99	15	hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table 2
26	A2 vs A1	md	-0.52 percent	-4.39 to 3.34		hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table S2
26	A2 vs A1	md	-0.41 percent	-3.52 to 2.70		hypothetical; randomized; sex:male; R0001289:Supplement Table S2
26	A2	percent change	-2.89 percent	-5.11 to -0.66	19	hypothetical; randomized; sex:male; R0001289:Supplement Table 2
26	A2 vs A1	md	-0.82 percent	-3.40 to 1.76		treatment policy; randomized; R0001289:Supplement Table S1
26	A2 vs A1	md	-0.77 percent	-5.00 to 3.45		hypothetical; randomized; sex:female; R0001289:Supplement Table S2
26	A2	percent change	-3.14 percent	-6.11 to -0.18	18	hypothetical; randomized; sex:female; R0001289:Supplement Table 2
26	A2	percent change	-3.36 percent	-5.17 to -1.56	48	treatment policy; randomized; R0001289:Supplement Table S1
26	A2 vs A1	md	-0.41 percent	-4.03 to 3.21		hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table S2
26	A2	percent change	-3.85 percent	-6.39 to -1.32	22	hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table 2
26	A2 vs A1	md	-0.49 percent	-3.11 to 2.12		hypothetical; randomized; R0001289:Table 2
26	A2 vs A1	md	-0.51 percent	-3.13 to 2.11		hypothetical; randomized; R0001289:Supplement Table S1
26	A2	percent change	-3.01 percent	-4.87 to -1.16		hypothetical; randomized; R0001289:Supplement Table S1
26	A3	percent change	-6.89 percent	-8.73 to -5.05	47	treatment policy; randomized; R0001289:Supplement Table S1
26	A3	percent change	-7.09 percent	-8.95 to -5.24		hypothetical; randomized; R0001289:Table 2
26	A3	percent change	-7.12 percent	-8.98 to -5.27		hypothetical; randomized; R0001289:Supplement Table S1
26	A3 vs A1	md	-4.60 percent	-7.21 to -1.98		hypothetical; randomized; R0001289:Table 2
26	A3 vs A1	md	-4.62 percent	-7.24 to -2.00		hypothetical; randomized; R0001289:Supplement Table S1
26	A3 vs A1	md	-4.35 percent	-6.97 to -1.73		treatment policy; randomized; R0001289:Supplement Table S1
26	A3	percent change	-5.04 percent	-7.68 to -2.40	19	hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table 2
26	A3 vs A1	md	-3.78 percent	-7.55 to 0.00		hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table S2
26	A3	percent change	-8.75 percent	-11.39 to -6.12	23	hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table 2
26	A3 vs A1	md	-5.31 percent	-8.99 to -1.63		hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table S2
26	A3	percent change	-9.05 percent	-11.99 to -6.10	20	hypothetical; randomized; sex:female; R0001289:Supplement Table 2
26	A3 vs A1	md	-6.68 percent	-10.89 to -2.47		hypothetical; randomized; sex:female; R0001289:Supplement Table S2
26	A3	percent change	-5.16 percent	-7.38 to -2.93	22	hypothetical; randomized; sex:male; R0001289:Supplement Table 2
26	A3 vs A1	md	-2.68 percent	-5.79 to 0.44		hypothetical; randomized; sex:male; R0001289:Supplement Table S2
26	A4 vs A1	md	-3.67 percent	-6.29 to -1.05		hypothetical; randomized; R0001289:Table 2
26	A4	percent change	-6.59 percent	-9.19 to -3.98	23	hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table 2
26	A4 vs A1	md	-3.15 percent	-6.81 to 0.52		hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table S2
26	A4	percent change	-5.63 percent	-8.34 to -2.93	18	hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table 2
26	A4 vs A1	md	-4.38 percent	-8.20 to -0.55		hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table S2
26	A4 vs A1	md	-3.63 percent	-6.24 to -1.02		treatment policy; randomized; R0001289:Supplement Table S1
26	A4 vs A1	md	-3.13 percent	-6.25 to -0.02		hypothetical; randomized; sex:male; R0001289:Supplement Table S2
26	A4 vs A1	md	-3.67 percent	-6.29 to -1.05		hypothetical; randomized; R0001289:Supplement Table S1
26	A4 vs A1	md	-4.39 percent	-8.61 to -0.18		hypothetical; randomized; sex:female; R0001289:Supplement Table S2
26	A4	percent change	-6.76 percent	-9.71 to -3.80	19	hypothetical; randomized; sex:female; R0001289:Supplement Table 2
26	A4	percent change	-6.17 percent	-8.02 to -4.33	46	treatment policy; randomized; R0001289:Supplement Table S1
26	A4	percent change	-5.61 percent	-7.84 to -3.39	22	hypothetical; randomized; sex:male; R0001289:Supplement Table 2
26	A4	percent change	-6.17 percent	-8.03 to -4.31		hypothetical; randomized; R0001289:Table 2
26	A4	percent change	-6.17 percent	-8.04 to -4.31		hypothetical; randomized; R0001289:Supplement Table S1
26	A5 vs A1	md	-6.87 percent	-9.48 to -4.26		hypothetical; randomized; R0001289:Table 2
26	A5 vs A1	md	-6.02 percent	-8.64 to -3.40		treatment policy; randomized; R0001289:Supplement Table S1
26	A5	percent change	-8.56 percent	-10.41 to -6.72	48	treatment policy; randomized; R0001289:Supplement Table S1
26	A5	percent change	-9.31 percent	-11.99 to -6.64	19	hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table 2
26	A5 vs A1	md	-8.05 percent	-11.85 to -4.25		hypothetical; randomized; bmi:32.5_or_more; R0001289:Supplement Table S2
26	A5 vs A1	md	-6.88 percent	-9.49 to -4.27		hypothetical; randomized; R0001289:Supplement Table S1
26	A5	percent change	-9.30 percent	-11.90 to -6.71	21	hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table 2
26	A5 vs A1	md	-5.86 percent	-9.52 to -2.20		hypothetical; randomized; bmi:less_than_32.5; R0001289:Supplement Table S2
26	A5	percent change	-9.38 percent	-11.23 to -7.54		hypothetical; randomized; R0001289:Supplement Table S1
26	A5	percent change	-9.36 percent	-11.21 to -7.52		hypothetical; randomized; R0001289:Table 2
26	A5	percent change	-12.55 percent	-15.51 to -9.58	19	hypothetical; randomized; sex:female; R0001289:Supplement Table 2
26	A5 vs A1	md	-10.18 percent	-14.40 to -5.96		hypothetical; randomized; sex:female; R0001289:Supplement Table S2
26	A5	percent change	-6.42 percent	-8.61 to -4.22	21	hypothetical; randomized; sex:male; R0001289:Supplement Table 2
26	A5 vs A1	md	-3.94 percent	-7.03 to -0.85		hypothetical; randomized; sex:male; R0001289:Supplement Table S2
36	A1	percent change	-1.39 percent	-3.52 to 0.74		hypothetical; randomized; R0001289:Table 3
36	A2 vs A1	md	-1.06 percent	-4.10 to 1.99		hypothetical; randomized; R0001289:Table 3
36	A2	percent change	-2.44 percent	-4.62 to -0.27		hypothetical; randomized; R0001289:Table 3
36	A3	percent change	-5.36 percent	-7.51 to -3.22		hypothetical; randomized; R0001289:Table 3
36	A3 vs A1	md	-3.98 percent	-7.00 to -0.96		hypothetical; randomized; R0001289:Table 3
36	A4	percent change	-5.36 percent	-7.51 to -3.21		hypothetical; randomized; R0001289:Table 3
36	A4 vs A1	md	-3.97 percent	-7.00 to -0.95		hypothetical; randomized; R0001289:Table 3
36	A5 vs A1	md	-8.08 percent	-11.10 to -5.05		hypothetical; randomized; R0001289:Table 3
36	A5	percent change	-9.46 percent	-11.61 to -7.32		hypothetical; randomized; R0001289:Table 3

Weight loss of 5 percent or more (18 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders	23.9	12.6 to 38.8	46	hypothetical; randomized; R0001289:Table 4
26	A2	responders	31.3	18.7 to 46.3	48	hypothetical; randomized; R0001289:Table 4
26	A2 vs A1	or	1.48	0.59 to 3.72		hypothetical; randomized; R0001289:Table 4
26	A3 vs A1	or	3.99	1.61 to 9.86		hypothetical; randomized; R0001289:Table 4
26	A3	responders	53.2	38.1 to 67.9	47	hypothetical; randomized; R0001289:Table 4
26	A4 vs A1	or	3.22	1.31 to 7.91		hypothetical; randomized; R0001289:Table 4
26	A4	responders	50.0	34.9 to 65.1	46	hypothetical; randomized; R0001289:Table 4
26	A5 vs A1	or	3.97	1.62 to 9.70		hypothetical; randomized; R0001289:Table 4
26	A5	responders	54.2	39.2 to 68.6	48	hypothetical; randomized; R0001289:Table 4
36	A1	responders	26.1	14.3 to 41.1	46	hypothetical; randomized; R0001289:Table 5
36	A2 vs A1	or	1.22	0.49 to 3.04		hypothetical; randomized; R0001289:Table 5
36	A2	responders	29.2	17.0 to 44.1	48	hypothetical; randomized; R0001289:Table 5
36	A3 vs A1	or	2.13	0.87 to 5.21		hypothetical; randomized; R0001289:Table 5
36	A3	responders	40.4	26.4 to 55.7	47	hypothetical; randomized; R0001289:Table 5
36	A4	responders	43.5	28.9 to 58.9	46	hypothetical; randomized; R0001289:Table 5
36	A4 vs A1	or	2.19	0.90 to 5.33		hypothetical; randomized; R0001289:Table 5
36	A5	responders	52.1	37.2 to 66.7	48	hypothetical; randomized; R0001289:Table 5
36	A5 vs A1	or	3.26	1.35 to 7.87		hypothetical; randomized; R0001289:Table 5

Weight loss of 10 percent or more (18 lines; O11B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders	6.5	1.4 to 17.9	46	hypothetical; randomized; R0001289:Table 4
26	A2	responders	6.3	1.3 to 17.2	48	hypothetical; randomized; R0001289:Table 4
26	A2 vs A1	or	0.96	0.18 to 5.13		hypothetical; randomized; R0001289:Table 4
26	A3	responders	25.5	13.9 to 40.4	47	hypothetical; randomized; R0001289:Table 4
26	A3 vs A1	or	5.76	1.46 to 22.72		hypothetical; randomized; R0001289:Table 4
26	A4	responders	26.1	14.3 to 41.1	46	hypothetical; randomized; R0001289:Table 4
26	A4 vs A1	or	5.33	1.36 to 20.91		hypothetical; randomized; R0001289:Table 4
26	A5	responders	41.7	27.6 to 56.8	48	hypothetical; randomized; R0001289:Table 4
26	A5 vs A1	or	11.77	3.10 to 44.66		hypothetical; randomized; R0001289:Table 4
36	A1	responders	6.5	1.4 to 17.9	46	hypothetical; randomized; R0001289:Table 5
36	A2	responders	8.3	2.3 to 20.0	48	hypothetical; randomized; R0001289:Table 5
36	A2 vs A1	or	1.32	0.28 to 6.35		hypothetical; randomized; R0001289:Table 5
36	A3	responders	21.3	10.7 to 35.7	47	hypothetical; randomized; R0001289:Table 5
36	A3 vs A1	or	4.27	1.07 to 17.01		hypothetical; randomized; R0001289:Table 5
36	A4	responders	21.7	11.0 to 36.4	46	hypothetical; randomized; R0001289:Table 5
36	A4 vs A1	or	4.07	1.03 to 16.12		hypothetical; randomized; R0001289:Table 5
36	A5	responders	35.4	22.2 to 50.5	48	hypothetical; randomized; R0001289:Table 5
36	A5 vs A1	or	8.43	2.23 to 31.83		hypothetical; randomized; R0001289:Table 5

Weight loss of 15 percent or more (10 lines; O11C)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders	0	0 to 7.7	46	hypothetical; randomized; R0001289:Table 4
26	A2	responders	0	0 to 7.4	48	hypothetical; randomized; R0001289:Table 4
26	A3	responders	12.8	4.8 to 25.7	47	hypothetical; randomized; R0001289:Table 4
26	A4	responders	10.9	3.6 to 23.6	46	hypothetical; randomized; R0001289:Table 4
26	A5	responders	22.9	12.0 to 37.3	48	hypothetical; randomized; R0001289:Table 4
36	A1	responders	0	0 to 7.7	46	hypothetical; randomized; R0001289:Table 5
36	A2	responders	2.1	0.1 to 11.1	48	hypothetical; randomized; R0001289:Table 5
36	A3	responders	17.0	7.7 to 30.8	47	hypothetical; randomized; R0001289:Table 5
36	A4	responders	13.0	4.9 to 26.3	46	hypothetical; randomized; R0001289:Table 5
36	A5	responders	20.8	10.5 to 35.0	48	hypothetical; randomized; R0001289:Table 5

Weight loss of 20 percent or more (3 lines; O11D)

Week	Arm	Statistic	Events / N	Detail
26	A1	responders	0 / 46	hypothetical; randomized; R0001289:Table 4
26	A2	responders	0 / 48	hypothetical; randomized; R0001289:Table 4
36	A1	responders	0 / 46	hypothetical; randomized; R0001289:Table 5

Weight loss of 25 percent or more (3 lines; O11E)

Week	Arm	Statistic	Events / N	Detail
26	A1	responders	0 / 46	hypothetical; randomized; R0001289:Table 4
26	A2	responders	0 / 48	hypothetical; randomized; R0001289:Table 4
36	A1	responders	0 / 46	hypothetical; randomized; R0001289:Table 5

All cause mortality (5 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; R0001289:Table 6
A2	events	1 / 48	not stated; safety; R0001289:Table 6
A3	events	0 / 47	not stated; safety; R0001289:Table 6
A4	events	0 / 46	not stated; safety; R0001289:Table 6
A5	events	0 / 48	not stated; safety; R0001289:Table 6

Hospitalization for heart failure (1 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A4	events				0 / 46	not stated; safety; R0001289:Table 6

Serious adverse events (5 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	1 / 46	not stated; safety; R0001289:Table 6
A2	events	1 / 48	not stated; safety; R0001289:Table 6
A3	events	2 / 47	not stated; safety; R0001289:Table 6
A4	events	0 / 46	not stated; safety; R0001289:Table 6
A5	events	3 / 48	not stated; safety; R0001289:Table 6

Discontinuation due to adverse events (5 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; R0001289:Table 6
A2	events	1 / 48	not stated; safety; R0001289:Table 6
A3	events	1 / 47	not stated; safety; R0001289:Table 6
A4	events	0 / 46	not stated; safety; R0001289:Table 6
A5	events	3 / 48	not stated; safety; R0001289:Table 6

Nausea (5 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	2 / 46	not stated; safety; R0001289:Table 6
A2	events	8 / 48	not stated; safety; R0001289:Table 6
A3	events	16 / 47	not stated; safety; R0001289:Table 6
A4	events	19 / 46	not stated; safety; R0001289:Table 6
A5	events	28 / 48	not stated; safety; R0001289:Table 6

Vomiting (5 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 46	not stated; safety; R0001289:Table 6
A2	events	9 / 48	not stated; safety; R0001289:Table 6
A3	events	14 / 47	not stated; safety; R0001289:Table 6
A4	events	18 / 46	not stated; safety; R0001289:Table 6
A5	events	21 / 48	not stated; safety; R0001289:Table 6

Diarrhea (5 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	4 / 46	not stated; safety; R0001289:Table 6
A2	events	9 / 48	not stated; safety; R0001289:Table 6
A3	events	10 / 47	not stated; safety; R0001289:Table 6
A4	events	12 / 46	not stated; safety; R0001289:Table 6
A5	events	9 / 48	not stated; safety; R0001289:Table 6

Constipation (5 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; R0001289:Supplement Table 6
A2	events	0 / 48	not stated; safety; R0001289:Supplement Table 6
A3	events	2 / 47	not stated; safety; R0001289:Supplement Table 6
A4	events	2 / 46	not stated; safety; R0001289:Supplement Table 6
A5	events	1 / 48	not stated; safety; R0001289:Supplement Table 6

Discontinuation due to gastrointestinal adverse events (5 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; R0001289:Supplement Table 6
A2	events	0 / 48	not stated; safety; R0001289:Supplement Table 6
A3	events	0 / 47	not stated; safety; R0001289:Supplement Table 6
A4	events	0 / 46	not stated; safety; R0001289:Supplement Table 6
A5	events	2 / 48	not stated; safety; R0001289:Supplement Table 6

Gallbladder and biliary disease (5 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; cholelithiasis; R0001289:Discussion
A2	events	0 / 48	not stated; safety; cholelithiasis; R0001289:Discussion
A3	events	0 / 47	not stated; safety; cholelithiasis; R0001289:Discussion
A4	events	0 / 46	not stated; safety; cholelithiasis; R0001289:Discussion
A5	events	0 / 48	not stated; safety; cholelithiasis; R0001289:Discussion

Acute pancreatitis (5 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; R0001289:Table 6
A2	events	0 / 48	not stated; safety; R0001289:Table 6
A3	events	0 / 47	not stated; safety; R0001289:Table 6
A4	events	0 / 46	not stated; safety; R0001289:Table 6
A5	events	0 / 48	not stated; safety; R0001289:Table 6

Medullary thyroid carcinoma (4 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; R0001289:Supplement Table S9
A2	events	0 / 48	not stated; safety; R0001289:Supplement Table S9
A4	events	0 / 46	not stated; safety; R0001289:Supplement Table S9
A5	events	0 / 48	not stated; safety; R0001289:Supplement Table S9

Thyroid cancer (any) (5 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; R0001289:Supplement Table 9
A2	events	0 / 48	not stated; safety; R0001289:Supplement Table 9
A3	events	1 / 47	not stated; safety; R0001289:Supplement Table 9
A4	events	0 / 46	not stated; safety; R0001289:Supplement Table 9
A5	events	0 / 48	not stated; safety; R0001289:Supplement Table 9

Death by suicide (5 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 46	not stated; safety; R0001289:Table 6
A2	events	0 / 48	not stated; safety; R0001289:Table 6
A3	events	0 / 47	not stated; safety; R0001289:Table 6
A4	events	0 / 46	not stated; safety; R0001289:Table 6
A5	events	0 / 48	not stated; safety; R0001289:Table 6