parallel randomized trial

NCT04440345

Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IBI362 in Overweight or Obese Subjects

Overweight or obesity without diabetes (adults)NCT04440345S001410

Design

Randomized: 60
Start year: 2020
Treatment: 12 weeks, follow-up 20 weeks
Countries: China (6 sites)
Sponsor: Innovent Biologics (industry)
Eligibility: age 18 to 75; BMI 28 or more, or 24 to below 28 with hyperphagia or comorbidity; diabetes excluded

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: safety
Missing data: MMRM without imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Mazdutide 3 mg subcutaneous once weekly IBI362 3.0 mg cohort	lifestyle: none	8	8
A10	Mazdutide 9 mg subcutaneous once weekly Mazdutide 9 mg cohort	lifestyle: none	8	8	8
A11	Placebo Placebo 9 mg cohort	lifestyle: none	4	4	4
A12	Pooled Pooled placebo 9 and 10 mg cohorts	lifestyle: none		8
A13	Pooled Pooled IBI362 3.0 to 6.0 mg cohorts	lifestyle: none		24
A2	Placebo Placebo 3.0 mg cohort	lifestyle: none	4	4
A3	Mazdutide 4.5 mg subcutaneous once weekly IBI362 4.5 mg cohort	lifestyle: none	8	8
A4	Placebo Placebo 4.5 mg cohort	lifestyle: none	4	4
A5	Mazdutide 6 mg subcutaneous once weekly IBI362 6.0 mg cohort	lifestyle: none	8	8
A6	Placebo Placebo 6.0 mg cohort	lifestyle: none	4	4
A7	Pooled Pooled placebo 3.0 to 6.0 mg cohorts	lifestyle: none		12
A8	mazdutide Mazdutide 10 mg cohort	lifestyle: none	8	8	7
A9	Placebo Placebo 10 mg cohort	lifestyle: none	4	4	2

Baseline characteristics

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

Characteristic	Statistic	Mazdutide 3 mg subcutaneous once weekly A1	Placebo A2	Mazdutide 4.5 mg subcutaneous once weekly A3	Placebo A4	Mazdutide 6 mg subcutaneous once weekly A5	Placebo A6	Mazdutide 10 mg cohort A8	Placebo A9	Mazdutide 9 mg subcutaneous once weekly A10	Placebo A11
age	mean (years)							36.0	34.3	37.9	45.5
age	median (years)	29.5	39.5	31.0	37.0	40.0	32.0
age	q1 (years)	24.0	31.0	23.5	32.5	23.0	28.5
age	q3 (years)	45.0	43.5	33.0	43.0	51.5	34.5
age	sd (years)							9.1	14.0	9.7	6.4
asian	n	8	4	8	4	8	4
asian	percent	100.0	100.0	100.0	100.0	100.0	100.0
bmi: 24 to less than 28	n	2	0	1	1	0	3
bmi: 24 to less than 28	percent	25.0	0	12.5	25.0	0	75.0
bmi: 28 or more	n	6	4	7	3	8	1
bmi: 28 or more	percent	75.0	100.0	87.5	75.0	100	25.0
bmi	mean (kg/m2)	29.3	30.6	32.4	29.1	31.7	29.0	31.8	29.1	30.1	30.1
bmi	sd (kg/m2)	2.2	1.2	3.4	3.7	2.0	5.1	5.1	4.6	3.8	1.7
female	n	5	3	2	2	3	3	6	3	6	2
female	percent	62.5	75.0	25.0	50.0	37.5	75.0	75.0	75.0	75.0	50.0
waist	mean (cm)	93.4	95.1	105.1	98.1	104.8	90.1	101.1	95.0	97.2	105.1
waist	sd (cm)	8.9	2.0	8.0	10.5	10.2	14.9	11.5	11.7	13.7	7.7
weight	mean (kg)	78.3	81.7	93.1	82.7	87.4	76.5	82.8	77.2	79.8	83.6
weight	sd (kg)	13.7	3.3	9.9	13.7	8.8	21.5	14.1	18.6	15.5	7.3

Results

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

Systolic blood pressure change (4 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
12	A1	change	-8.26 mmHg	-14.77 to -1.76	8	not stated; modified itt; R0014885:Table 4
12	A3	change	-5.80 mmHg	-12.34 to 0.73	8	not stated; modified itt; R0014885:Table 4
12	A5	change	-5.59 mmHg	-12.56 to 1.38	7	not stated; modified itt; R0014885:Table 4
12	A7	change	2.02 mmHg	-3.40 to 7.44	12	not stated; modified itt; R0014885:Table 4

Percent body weight change (13 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
12	A1	percent change	-4.81 percent		-6.61 to -3.02	8	not stated; modified itt; R0014885:Table 4
12	A1 vs A7	md	-5.42 percent		-7.71 to -3.12		not stated; modified itt; R0014885:Table 4
12	A10	percent change	-11.7 percent	1.5			not stated; modified itt; R0013351:Table 4
12	A10 vs A12	md	-9.8 percent		-14.4 to -5.3		not stated; modified itt; R0013351:Table 4
12	A12	percent change	-1.8 percent	1.6			not stated; modified itt; R0013351:Table 4
12	A3	percent change	-6.40 percent		-8.23 to -4.58	8	not stated; modified itt; R0014885:Table 4
12	A3 vs A7	md	-7.01 percent		-9.39 to -4.63		not stated; modified itt; R0014885:Table 4
12	A5	percent change	-6.05 percent		-7.91 to -4.18	7	not stated; modified itt; R0014885:Table 4
12	A5 vs A7	md	-6.65 percent		-9.03 to -4.27		not stated; modified itt; R0014885:Table 4
12	A7	percent change	0.60 percent		-0.86 to 2.07	12	not stated; modified itt; R0014885:Table 4
16	A12	percent change	-3.3 percent	1.9			not stated; modified itt; R0013351:Table 4
16	A8	percent change	-9.5 percent	1.7			not stated; modified itt; R0013351:Table 4
16	A8 vs A12	md	-6.2 percent		-11.5 to -0.9		not stated; modified itt; R0013351:Table 4

Weight loss of 5 percent or more (4 lines; O11A)

Week	Arm	Statistic	Events / N	Detail
12	A11	responders	0 / 4	not stated; modified itt; R0013351:Results
12	A13	responders	13 / 24	not stated; modified itt; R0014885:Results
12	A7	responders	0 / 12	not stated; modified itt; R0014885:Results
16	A9	responders	0 / 4	not stated; modified itt; R0013351:Results

Weight loss of 10 percent or more (5 lines; O11B)

Week	Arm	Statistic	Events / N	Detail
12	A10	responders	4 / 8	not stated; modified itt; R0013351:Results
12	A11	responders	0 / 4	not stated; modified itt; R0013351:Results
12	A7	responders	0 / 12	not stated; modified itt; R0014885:Results
16	A8	responders	4 / 8	not stated; modified itt; R0013351:Results
16	A9	responders	0 / 4	not stated; modified itt; R0013351:Results

Weight loss of 15 percent or more (5 lines; O11C)

Week	Arm	Statistic	Events / N	Detail
12	A10	responders	2 / 8	not stated; modified itt; R0013351:Results
12	A11	responders	0 / 4	not stated; modified itt; R0013351:Results
12	A7	responders	0 / 12	not stated; modified itt; R0014885:Results
16	A8	responders	2 / 8	not stated; modified itt; R0013351:Results
16	A9	responders	0 / 4	not stated; modified itt; R0013351:Results

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A2	events	0 / 4	not stated; safety; R0014885:Supplement Table S2
A4	events	0 / 4	not stated; safety; R0014885:Supplement Table S2
A5	events	0 / 8	not stated; safety; R0014885:Supplement Table S2
A6	events	0 / 4	not stated; safety; R0014885:Supplement Table S2

All cause mortality (10 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Table 2
A10	events	0 / 8	not stated; safety; R0013351:Table 2
A11	events	0 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Table 2
A3	events	0 / 8	not stated; safety; R0014885:Table 2
A4	events	0 / 4	not stated; safety; R0014885:Table 2
A5	events	0 / 8	not stated; safety; R0014885:Table 2
A6	events	0 / 4	not stated; safety; R0014885:Table 2
A8	events	0 / 8	not stated; safety; R0013351:Table 2
A9	events	0 / 4	not stated; safety; R0013351:Table 2

Hospitalization for heart failure (10 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Table 2
A10	events	0 / 8	not stated; safety; R0013351:Table 2
A11	events	0 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Table 2
A3	events	0 / 8	not stated; safety; R0014885:Table 2
A4	events	0 / 4	not stated; safety; R0014885:Table 2
A5	events	0 / 8	not stated; safety; R0014885:Table 2
A6	events	0 / 4	not stated; safety; R0014885:Table 2
A8	events	0 / 8	not stated; safety; R0013351:Table 2
A9	events	0 / 4	not stated; safety; R0013351:Table 2

Heart failure events (6 lines; O23B)

Arm	Statistic	Events / N	Detail
A11	events	0 / 4	not stated; safety; R0013351:Supplement Table S1
A2	events	0 / 4	not stated; safety; R0014885:Supplement Table S2
A4	events	0 / 4	not stated; safety; R0014885:Supplement Table S2
A5	events	0 / 8	not stated; safety; R0014885:Supplement Table S2
A6	events	0 / 4	not stated; safety; R0014885:Supplement Table S2
A8	events	0 / 8	not stated; safety; R0013351:Supplement Table S1

Serious adverse events (10 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Table 2
A10	events	0 / 8	not stated; safety; R0013351:Table 2
A11	events	0 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Table 2
A3	events	0 / 8	not stated; safety; R0014885:Table 2
A4	events	0 / 4	not stated; safety; R0014885:Table 2
A5	events	0 / 8	not stated; safety; R0014885:Table 2
A6	events	0 / 4	not stated; safety; R0014885:Table 2
A8	events	0 / 8	not stated; safety; R0013351:Table 2
A9	events	0 / 4	not stated; safety; R0013351:Table 2

Discontinuation due to adverse events (16 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Abstract
A1	events	0 / 8	not stated; safety; R0014885:Results
A10	events	0 / 8	not stated; safety; R0013351:Table 2
A11	events	0 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Results
A2	events	0 / 4	not stated; safety; R0014885:Abstract
A3	events	0 / 8	not stated; safety; R0014885:Abstract
A3	events	0 / 8	not stated; safety; R0014885:Results
A4	events	0 / 4	not stated; safety; R0014885:Abstract
A4	events	0 / 4	not stated; safety; R0014885:Results
A5	events	0 / 8	not stated; safety; R0014885:Results
A5	events	0 / 8	not stated; safety; R0014885:Abstract
A6	events	0 / 4	not stated; safety; R0014885:Abstract
A6	events	0 / 4	not stated; safety; R0014885:Results
A8	events	0 / 8	not stated; safety; R0013351:Table 2
A9	events	0 / 4	not stated; safety; R0013351:Table 2

Nausea (10 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Table 2
A10	events	5 / 8	not stated; safety; R0013351:Table 2
A11	events	0 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Table 2
A3	events	3 / 8	not stated; safety; R0014885:Table 2
A4	events	1 / 4	not stated; safety; R0014885:Table 2
A5	events	1 / 8	not stated; safety; R0014885:Table 2
A6	events	0 / 4	not stated; safety; R0014885:Table 2
A8	events	1 / 8	not stated; safety; R0013351:Table 2
A9	events	1 / 4	not stated; safety; R0013351:Table 2

Vomiting (10 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 8	not stated; safety; R0014885:Table 2
A10	events	3 / 8	not stated; safety; R0013351:Table 2
A11	events	0 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Table 2
A3	events	0 / 8	not stated; safety; R0014885:Table 2
A4	events	0 / 4	not stated; safety; R0014885:Table 2
A5	events	1 / 8	not stated; safety; R0014885:Table 2
A6	events	0 / 4	not stated; safety; R0014885:Table 2
A8	events	3 / 8	not stated; safety; R0013351:Table 2
A9	events	0 / 4	not stated; safety; R0013351:Table 2

Diarrhea (10 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Table 2
A10	events	2 / 8	not stated; safety; R0013351:Table 2
A11	events	2 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Table 2
A3	events	3 / 8	not stated; safety; R0014885:Table 2
A4	events	1 / 4	not stated; safety; R0014885:Table 2
A5	events	3 / 8	not stated; safety; R0014885:Table 2
A6	events	0 / 4	not stated; safety; R0014885:Table 2
A8	events	4 / 8	not stated; safety; R0013351:Table 2
A9	events	2 / 4	not stated; safety; R0013351:Table 2

Constipation (10 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	1 / 8	not stated; safety; R0014885:Table 2
A10	events	1 / 8	not stated; safety; R0013351:Supplement Table S1
A11	events	0 / 4	not stated; safety; R0013351:Supplement Table S1
A2	events	0 / 4	not stated; safety; R0014885:Table 2
A3	events	0 / 8	not stated; safety; R0014885:Table 2
A4	events	0 / 4	not stated; safety; R0014885:Table 2
A5	events	0 / 8	not stated; safety; R0014885:Table 2
A6	events	1 / 4	not stated; safety; R0014885:Table 2
A8	events	0 / 8	not stated; safety; R0013351:Supplement Table S1
A9	events	0 / 4	not stated; safety; R0013351:Supplement Table S1

Discontinuation due to gastrointestinal adverse events (16 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Results
A1	events	0 / 8	not stated; safety; R0014885:Abstract
A10	events	0 / 8	not stated; safety; R0013351:Table 2
A11	events	0 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Abstract
A2	events	0 / 4	not stated; safety; R0014885:Results
A3	events	0 / 8	not stated; safety; R0014885:Results
A3	events	0 / 8	not stated; safety; R0014885:Abstract
A4	events	0 / 4	not stated; safety; R0014885:Results
A4	events	0 / 4	not stated; safety; R0014885:Abstract
A5	events	0 / 8	not stated; safety; R0014885:Results
A5	events	0 / 8	not stated; safety; R0014885:Abstract
A6	events	0 / 4	not stated; safety; R0014885:Abstract
A6	events	0 / 4	not stated; safety; R0014885:Results
A8	events	0 / 8	not stated; safety; R0013351:Table 2
A9	events	0 / 4	not stated; safety; R0013351:Table 2

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A10	events	1 / 8	not stated; safety; cholelithiasis; R0013351:Supplement Table S1
A11	events	0 / 4	not stated; safety; cholelithiasis; R0013351:Supplement Table S1
A8	events	0 / 8	not stated; safety; cholelithiasis; R0013351:Supplement Table S1
A9	events	0 / 4	not stated; safety; cholelithiasis; R0013351:Supplement Table S1

Acute pancreatitis (10 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; pancreatitis; R0014885:Results
A10	events	0 / 8	not stated; safety; pancreatitis; R0013351:Results
A11	events	0 / 4	not stated; safety; pancreatitis; R0013351:Results
A2	events	0 / 4	not stated; safety; pancreatitis; R0014885:Results
A3	events	0 / 8	not stated; safety; pancreatitis; R0014885:Results
A4	events	0 / 4	not stated; safety; pancreatitis; R0014885:Results
A5	events	0 / 8	not stated; safety; pancreatitis; R0014885:Results
A6	events	0 / 4	not stated; safety; pancreatitis; R0014885:Results
A8	events	0 / 8	not stated; safety; pancreatitis; R0013351:Results
A9	events	0 / 4	not stated; safety; pancreatitis; R0013351:Results

Medullary thyroid carcinoma (10 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Results
A10	events	0 / 8	not stated; safety; R0013351:Results
A11	events	0 / 4	not stated; safety; R0013351:Results
A2	events	0 / 4	not stated; safety; R0014885:Results
A3	events	0 / 8	not stated; safety; R0014885:Results
A4	events	0 / 4	not stated; safety; R0014885:Results
A5	events	0 / 8	not stated; safety; R0014885:Results
A6	events	0 / 4	not stated; safety; R0014885:Results
A8	events	0 / 8	not stated; safety; R0013351:Results
A9	events	0 / 4	not stated; safety; R0013351:Results

Thyroid cancer (any) (10 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Results
A10	events	0 / 8	not stated; safety; R0013351:Results
A11	events	0 / 4	not stated; safety; R0013351:Results
A2	events	0 / 4	not stated; safety; R0014885:Results
A3	events	0 / 8	not stated; safety; R0014885:Results
A4	events	0 / 4	not stated; safety; R0014885:Results
A5	events	0 / 8	not stated; safety; R0014885:Results
A6	events	0 / 4	not stated; safety; R0014885:Results
A8	events	0 / 8	not stated; safety; R0013351:Results
A9	events	0 / 4	not stated; safety; R0013351:Results

Nonarteritic anterior ischemic optic neuropathy (3 lines; O34)

Arm	Statistic	Events / N	Detail
A10	events	0 / 8	not stated; safety; R0013351:Supplement Table S1
A11	events	0 / 4	not stated; safety; R0013351:Supplement Table S1
A9	events	0 / 4	not stated; safety; R0013351:Supplement Table S1

Suicidal ideation or behavior (8 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Supplement Table S2
A11	events	0 / 4	not stated; safety; R0013351:Supplement Table S1
A2	events	0 / 4	not stated; safety; R0014885:Supplement Table S2
A4	events	0 / 4	not stated; safety; R0014885:Supplement Table S2
A5	events	0 / 8	not stated; safety; R0014885:Supplement Table S2
A6	events	0 / 4	not stated; safety; R0014885:Supplement Table S2
A8	events	0 / 8	not stated; safety; R0013351:Supplement Table S1
A9	events	0 / 4	not stated; safety; R0013351:Supplement Table S1

Death by suicide (10 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 8	not stated; safety; R0014885:Table 2
A10	events	0 / 8	not stated; safety; R0013351:Table 2
A11	events	0 / 4	not stated; safety; R0013351:Table 2
A2	events	0 / 4	not stated; safety; R0014885:Table 2
A3	events	0 / 8	not stated; safety; R0014885:Table 2
A4	events	0 / 4	not stated; safety; R0014885:Table 2
A5	events	0 / 8	not stated; safety; R0014885:Table 2
A6	events	0 / 4	not stated; safety; R0014885:Table 2
A8	events	0 / 8	not stated; safety; R0013351:Table 2
A9	events	0 / 4	not stated; safety; R0013351:Table 2