parallel randomized trial

NCT03856047

Investigation of Safety and Efficacy of NNC0174-0833 for Weight Management - a Dose Finding Trial.

Overweight or obesity without diabetes (adults)NCT03856047S001532

Design

Randomized: 706
Start year: 2019
Treatment: 26 weeks, follow-up 32 weeks
Countries: multinational
Sponsor: Novo Nordisk (industry)
Eligibility: age 18 or older; BMI 30 or more, or 27 or more with hypertension or dyslipidemia; no diabetes

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: full analysis
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Cagrilintide Cagrilintide 0.3 mg QW	lifestyle: standard	101	101	93
A2	Cagrilintide Cagrilintide 0.6 mg QW	lifestyle: standard	100	100	92
A3	Cagrilintide Cagrilintide 1.2 mg QW	lifestyle: standard	102	102	90
A4	Cagrilintide Cagrilintide 2.4 mg QW	lifestyle: standard	102	102	93
A5	Cagrilintide Cagrilintide 4.5 mg QW	lifestyle: standard	101	101	94
A6	Liraglutide 3.0 mg subcutaneous once daily Liraglutide 3.0 mg QD	lifestyle: standard	99	99	86
A7	Placebo Placebo pooled	lifestyle: standard	101	101	85

Baseline characteristics

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

Characteristic	Statistic	Cagrilintide A1	Cagrilintide A2	Cagrilintide A3	Cagrilintide A4	Cagrilintide A5	Liraglutide 3.0 mg subcutaneous once daily A6	Placebo A7
age	mean (years)	53.5	53.2	52.1	52.7	51.5	51.5	51.4
age	sd (years)	10.3	11.0	8.7	9.8	12.7	9.3	11.9
asian	n	13	14	15	11	9	13	17
asian	percent	12.9	14.0	14.7	10.8	8.9	13.1	16.8
black	n	9	5	8	9	5	0	9
black	percent	8.9	5.0	7.8	8.8	5.0		8.9
bmi	mean (kg/m2)	38.4	37.2	37.1	37.9	38.4	38.4	37.4
bmi	sd (kg/m2)	7.5	6.9	6.2	7.6	7.7	7.4	5.7
female	n	56	62	63	75	56	65	59
female	percent	55.4	62.0	61.8	73.5	55.4	65.7	58.4
hba1c	mean (percent)	5.6	5.6	5.6	5.6	5.6	5.6	5.6
hba1c	sd (percent)	0.4	0.4	0.4	0.4	0.3	0.4	0.4
hispanic	n	2	1	4	2	3	5	4
hispanic	percent	2.0	1.0	3.9	2.0	3.0	5.1	4.0
other race american indian alaska native	n	1	1	0	0	0	0	0
other race american indian alaska native	percent	1.0	1.0
other race other	n	1	5	4	2	4	4	4
other race other	percent	1.0	5.0	3.9	2.0	4.0	4.0	4.0
sbp	mean (mmHg)	134.1	131.9	132.5	129.4	132.7	131.8	131.9
sbp	sd (mmHg)	15.7	15.9	14.8	12.6	15.7	13.7	13.2
waist	mean (cm)	116.2	114.5	113.5	113.7	118.9	116.3	114.7
waist	sd (cm)	16.0	15.1	15.0	14.6	17.6	15.4	13.7
weight	mean (kg)	109.8	106.2	104.4	106.8	111.0	107.8	106.2
weight	sd (kg)	25.1	23.8	21.5	24.1	28.6	24.1	21.6
white	n	77	75	75	80	83	82	71
white	percent	76.2	75.0	73.5	78.4	82.2	82.8	70.3

Analyses this trial contributes to

Results

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

Systolic blood pressure change (24 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A7	md	-1.0 mmHg		-4.5 to 2.5		hypothetical; full analysis; R0017871:Table 2
26	A1	change	-4.9 mmHg	8.7		63	while on treatment; safety; registry:outcomes
26	A1 vs A6	md	-0.4 mmHg		-3.9 to 3.2		hypothetical; full analysis; R0017871:Table 2
26	A1	change	-4.7 mmHg	1.3		101	hypothetical; full analysis; R0017871:Table 2
26	A2 vs A6	md	-0.6 mmHg		-4.2 to 2.9		hypothetical; full analysis; R0017871:Table 2
26	A2 vs A7	md	-1.3 mmHg		-4.9 to 2.3		hypothetical; full analysis; R0017871:Table 2
26	A2	change	-0.9 mmHg	8.1		63	while on treatment; safety; registry:outcomes
26	A2	change	-4.9 mmHg	1.3		100	hypothetical; full analysis; R0017871:Table 2
26	A3	change	-4.9 mmHg	9.7		58	while on treatment; safety; registry:outcomes
26	A3	change	-5.5 mmHg	1.4		102	hypothetical; full analysis; R0017871:Table 2
26	A3 vs A6	md	-1.2 mmHg		-4.9 to 2.5		hypothetical; full analysis; R0017871:Table 2
26	A3 vs A7	md	-1.8 mmHg		-5.5 to 1.9		hypothetical; full analysis; R0017871:Table 2
26	A4	change	-5.0 mmHg	8.4		66	while on treatment; safety; registry:outcomes
26	A4 vs A7	md	-4.3 mmHg		-7.8 to -0.8		hypothetical; full analysis; R0017871:Table 2
26	A4 vs A6	md	-3.7 mmHg		-7.2 to -0.1		hypothetical; full analysis; R0017871:Table 2
26	A4	change	-8.0 mmHg	1.3		102	hypothetical; full analysis; R0017871:Table 2
26	A5	change	-6.5 mmHg	1.3		101	hypothetical; full analysis; R0017871:Table 2
26	A5 vs A6	md	-2.2 mmHg		-5.7 to 1.3		hypothetical; full analysis; R0017871:Table 2
26	A5 vs A7	md	-2.8 mmHg		-6.4 to 0.7		hypothetical; full analysis; R0017871:Table 2
26	A5	change	-6.2 mmHg	8.5		68	while on treatment; safety; registry:outcomes
26	A6 vs A7	md	-0.7 mmHg		-4.2 to 2.9		hypothetical; full analysis; R0017871:Table 2
26	A6	change	-4.3 mmHg	1.3		99	hypothetical; full analysis; R0017871:Table 2
26	A7	change	-3.8 mmHg	7.1		47	while on treatment; safety; registry:outcomes
26	A7	change	-3.6 mmHg	1.3		101	hypothetical; full analysis; R0017871:Table 2

Percent body weight change (37 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A7	md	-3.26 percent		-4.77 to -1.75		treatment policy; full analysis; R0017871:Figure 2G
26	A1	percent change	-6.1 percent	3.9		96	treatment policy; full analysis; registry:outcomes
26	A1 vs A7	md	-3.0 percent		-4.6 to -1.4		hypothetical; full analysis; R0017871:Table 2
26	A1	percent change	-6.0 percent	0.6		101	hypothetical; full analysis; R0017871:Table 2
26	A1 vs A6	md	3.0 percent		1.4 to 4.6		hypothetical; full analysis; R0017871:Table 2
26	A1 vs A6	md	2.53 percent		0.87 to 4.18		treatment policy; full analysis; R0017871:Figure 2H
26	A2 vs A6	md	1.81 percent		0.16 to 3.46		treatment policy; full analysis; R0017871:Figure 2H
26	A2	percent change	-6.8 percent	0.6		100	hypothetical; full analysis; R0017871:Table 2
26	A2 vs A6	md	2.2 percent		0.6 to 3.8		hypothetical; full analysis; R0017871:Table 2
26	A2 vs A7	md	-3.8 percent		-5.4 to -2.2		hypothetical; full analysis; R0017871:Table 2
26	A2	percent change	-6.9 percent	5.4		97	treatment policy; full analysis; registry:outcomes
26	A2 vs A7	md	-4.01 percent		-5.52 to -2.50		treatment policy; full analysis; R0017871:Figure 2G
26	A3 vs A6	md	-0.1 percent		-1.8 to 1.6		hypothetical; full analysis; R0017871:Table 2
26	A3 vs A7	md	-5.62 percent		-7.13 to -4.11		treatment policy; full analysis; R0017871:Figure 2G
26	A3 vs A6	md	-0.17 percent		-1.82 to 1.48		treatment policy; full analysis; R0017871:Figure 2H
26	A3	percent change	-8.5 percent	5.4		98	treatment policy; full analysis; registry:outcomes
26	A3	percent change	-9.1 percent	0.7		102	hypothetical; full analysis; R0017871:Table 2
26	A3 vs A7	md	-6.1 percent		-7.8 to -4.4		hypothetical; full analysis; R0017871:Table 2
26	A4	percent change	-9.5 percent	6.2		99	treatment policy; full analysis; registry:outcomes
26	A4	percent change	-9.7 percent	0.6		102	hypothetical; full analysis; R0017871:Table 2
26	A4 vs A6	md	-0.7 percent		-2.3 to 0.9		hypothetical; full analysis; R0017871:Table 2
26	A4 vs A7	md	-6.7 percent		-8.3 to -5.1		hypothetical; full analysis; R0017871:Table 2
26	A4 vs A6	md	-1.10 percent		-2.75 to 0.54		treatment policy; full analysis; R0017871:Figure 2H
26	A4 vs A7	md	-6.64 percent		-8.15 to -5.14		treatment policy; full analysis; R0017871:Figure 2G
26	A5	percent change	-10.8 percent	5.5		97	treatment policy; full analysis; registry:outcomes
26	A5 vs A7	md	-7.8 percent		-9.4 to -6.2		hypothetical; full analysis; R0017871:Table 2
26	A5 vs A6	md	-1.8 percent		-3.5 to -0.2		hypothetical; full analysis; R0017871:Table 2
26	A5	percent change	-10.8 percent	0.6		101	hypothetical; full analysis; R0017871:Table 2
26	A5 vs A7	md	-7.74 percent		-9.25 to -6.23		treatment policy; full analysis; R0017871:Figure 2G
26	A5 vs A6	md	-2.33 percent		-3.98 to -0.68		treatment policy; full analysis; R0017871:Figure 2H
26	A6	percent change	-9.0 percent	0.6		99	hypothetical; full analysis; R0017871:Table 2
26	A6	percent change	-8.5 percent	5.6		95	treatment policy; full analysis; registry:outcomes
26	A6 vs A7	md	-5.53 percent		-7.05 to -4.01		treatment policy; full analysis; R0017871:Figure 2G
26	A6 vs A7	md	-6.0 percent		-7.6 to -4.4		hypothetical; full analysis; R0017871:Table 2
26	A7	percent change	-3.0 percent	0.6		101	hypothetical; full analysis; R0017871:Table 2
26	A7	percent change	-3.0 percent	5.2		95	treatment policy; full analysis; registry:outcomes
32	A6	percent change	-7.2 percent				not stated; other; R0017871:Results

Weight loss of 5 percent or more (14 lines; O11A)

Week	Arm	Statistic	Estimate	Events / N	Detail
26	A1	responders	57.5	101	hypothetical; full analysis; R0017871:Table 2
26	A1	responders	57.47	83	not stated; full analysis; registry:outcomes
26	A2	responders	62.0	100	hypothetical; full analysis; R0017871:Table 2
26	A2	responders	61.98	82	not stated; full analysis; registry:outcomes
26	A3	responders	75.84	72	not stated; full analysis; registry:outcomes
26	A3	responders	75.8	102	hypothetical; full analysis; R0017871:Table 2
26	A4	responders	74.1	102	hypothetical; full analysis; R0017871:Table 2
26	A4	responders	74.12	80	not stated; full analysis; registry:outcomes
26	A5	responders	88.7	101	hypothetical; full analysis; R0017871:Table 2
26	A5	responders	88.74	80	not stated; full analysis; registry:outcomes
26	A6	responders	76.16	78	not stated; full analysis; registry:outcomes
26	A6	responders	76.2	99	hypothetical; full analysis; R0017871:Table 2
26	A7	responders	30.90	79	not stated; full analysis; registry:outcomes
26	A7	responders	30.9	101	hypothetical; full analysis; R0017871:Table 2

Weight loss of 10 percent or more (14 lines; O11B)

Week	Arm	Statistic	Estimate	Events / N	Detail
26	A1	responders	15.3	101	hypothetical; full analysis; R0017871:Table 2
26	A1	responders	15.28	83	not stated; full analysis; registry:outcomes
26	A2	responders	24.1	100	hypothetical; full analysis; R0017871:Table 2
26	A2	responders	24.06	82	not stated; full analysis; registry:outcomes
26	A3	responders	35.8	102	hypothetical; full analysis; R0017871:Table 2
26	A3	responders	35.79	72	not stated; full analysis; registry:outcomes
26	A4	responders	44.0	102	hypothetical; full analysis; R0017871:Table 2
26	A4	responders	43.97	80	not stated; full analysis; registry:outcomes
26	A5	responders	53.49	80	not stated; full analysis; registry:outcomes
26	A5	responders	53.5	101	hypothetical; full analysis; R0017871:Table 2
26	A6	responders	39.4	99	hypothetical; full analysis; R0017871:Table 2
26	A6	responders	39.43	78	not stated; full analysis; registry:outcomes
26	A7	responders	10.4	101	hypothetical; full analysis; R0017871:Table 2
26	A7	responders	10.44	79	not stated; full analysis; registry:outcomes

Weight loss of 15 percent or more (7 lines; O11C)

Week	Arm	Statistic	Estimate	Events / N	Detail
26	A1	responders	3.1	101	hypothetical; full analysis; R0017871:Figure 3
26	A2	responders	5.4	100	hypothetical; full analysis; R0017871:Figure 3
26	A3	responders	14.5	102	hypothetical; full analysis; R0017871:Figure 3
26	A4	responders	21.7	102	hypothetical; full analysis; R0017871:Figure 3
26	A5	responders	18.7	101	hypothetical; full analysis; R0017871:Results
26	A6	responders	14.0	99	hypothetical; full analysis; R0017871:Results
26	A7	responders	2.9	101	hypothetical; full analysis; R0017871:Results

All cause mortality (14 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 101	not stated; safety; registry:adverse_events
A1	events	0 / 101	while on treatment; safety; R0017871:Table 3
A2	events	0 / 100	not stated; safety; registry:adverse_events
A2	events	0 / 100	while on treatment; safety; R0017871:Table 3
A3	events	0 / 102	while on treatment; safety; R0017871:Table 3
A3	events	0 / 102	not stated; safety; registry:adverse_events
A4	events	0 / 102	while on treatment; safety; R0017871:Table 3
A4	events	0 / 102	not stated; safety; registry:adverse_events
A5	events	0 / 101	while on treatment; safety; R0017871:Table 3
A5	events	0 / 101	not stated; safety; registry:adverse_events
A6	events	0 / 99	while on treatment; safety; R0017871:Table 3
A6	events	0 / 99	not stated; safety; registry:adverse_events
A7	events	0 / 101	not stated; safety; registry:adverse_events
A7	events	0 / 101	while on treatment; safety; R0017871:Table 3

Serious adverse events (7 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	6 / 101	while on treatment; safety; R0017871:Table 3
A2	events	2 / 100	while on treatment; safety; R0017871:Table 3
A3	events	7 / 102	while on treatment; safety; R0017871:Table 3
A4	events	3 / 102	while on treatment; safety; R0017871:Table 3
A5	events	4 / 101	while on treatment; safety; R0017871:Table 3
A6	events	4 / 99	while on treatment; safety; R0017871:Table 3
A7	events	3 / 101	while on treatment; safety; R0017871:Table 3

Discontinuation due to adverse events (7 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	2 / 101	while on treatment; safety; R0017871:Table 3
A2	events	4 / 100	while on treatment; safety; R0017871:Table 3
A3	events	6 / 102	while on treatment; safety; R0017871:Table 3
A4	events	6 / 102	while on treatment; safety; R0017871:Table 3
A5	events	1 / 101	while on treatment; safety; R0017871:Table 3
A6	events	7 / 99	while on treatment; safety; R0017871:Table 3
A7	events	3 / 101	while on treatment; safety; R0017871:Table 3

Nausea (7 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	20 / 101	while on treatment; safety; R0017871:Table 3
A2	events	27 / 100	while on treatment; safety; R0017871:Table 3
A3	events	37 / 102	while on treatment; safety; R0017871:Table 3
A4	events	32 / 102	while on treatment; safety; R0017871:Table 3
A5	events	47 / 101	while on treatment; safety; R0017871:Table 3
A6	events	39 / 99	while on treatment; safety; R0017871:Table 3
A7	events	18 / 101	while on treatment; safety; R0017871:Table 3

Vomiting (7 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	6 / 101	while on treatment; safety; R0017871:Table 3
A2	events	6 / 100	while on treatment; safety; R0017871:Table 3
A3	events	5 / 102	while on treatment; safety; R0017871:Table 3
A4	events	9 / 102	while on treatment; safety; R0017871:Table 3
A5	events	8 / 101	while on treatment; safety; R0017871:Table 3
A6	events	20 / 99	while on treatment; safety; R0017871:Table 3
A7	events	3 / 101	while on treatment; safety; R0017871:Table 3

Diarrhea (7 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	15 / 101	while on treatment; safety; R0017871:Table 3
A2	events	10 / 100	while on treatment; safety; R0017871:Table 3
A3	events	8 / 102	while on treatment; safety; R0017871:Table 3
A4	events	18 / 102	while on treatment; safety; R0017871:Table 3
A5	events	7 / 101	while on treatment; safety; R0017871:Table 3
A6	events	18 / 99	while on treatment; safety; R0017871:Table 3
A7	events	9 / 101	while on treatment; safety; R0017871:Table 3

Constipation (7 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	11 / 101	while on treatment; safety; R0017871:Table 3
A2	events	9 / 100	while on treatment; safety; R0017871:Table 3
A3	events	8 / 102	while on treatment; safety; R0017871:Table 3
A4	events	17 / 102	while on treatment; safety; R0017871:Table 3
A5	events	21 / 101	while on treatment; safety; R0017871:Table 3
A6	events	26 / 99	while on treatment; safety; R0017871:Table 3
A7	events	7 / 101	while on treatment; safety; R0017871:Table 3

Discontinuation due to gastrointestinal adverse events (2 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A3	events				2 / 102	not stated; safety; R0017871:Results
	A4	events				1 / 102	not stated; safety; R0017871:Results

Gallbladder and biliary disease (7 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 101	while on treatment; safety; R0017871:Table 3
A2	events	1 / 100	while on treatment; safety; R0017871:Table 3
A3	events	2 / 102	while on treatment; safety; R0017871:Table 3
A4	events	1 / 102	while on treatment; safety; R0017871:Table 3
A5	events	1 / 101	while on treatment; safety; R0017871:Table 3
A6	events	1 / 99	while on treatment; safety; R0017871:Table 3
A7	events	0 / 101	while on treatment; safety; R0017871:Table 3

Acute pancreatitis (7 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 101	not stated; safety; R0017871:Results
A2	events	0 / 100	not stated; safety; R0017871:Results
A3	events	0 / 102	not stated; safety; R0017871:Results
A4	events	0 / 102	not stated; safety; R0017871:Results
A5	events	0 / 101	not stated; safety; R0017871:Results
A6	events	1 / 99	not stated; safety; R0017871:Results
A7	events	0 / 101	not stated; safety; R0017871:Results

Any cancer (7 lines; O39)

Arm	Statistic	Events / N	Detail
A1	events	0 / 101	treatment policy; safety; R0017871:Results
A2	events	1 / 100	treatment policy; safety; R0017871:Results
A3	events	2 / 102	treatment policy; safety; R0017871:Results
A4	events	0 / 102	treatment policy; safety; R0017871:Results
A5	events	0 / 101	treatment policy; safety; R0017871:Results
A6	events	1 / 99	treatment policy; safety; R0017871:Results
A7	events	1 / 101	treatment policy; safety; R0017871:Results