parallel randomized trial

NCT04478708

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 133 in Subjects With Obesity

Overweight or obesity without diabetes (adults)NCT04478708S001178

Design

Randomized: 75
Start year: 2020
Treatment: 12 weeks, follow-up 29.43 weeks
Countries: United States (3 sites)
Sponsor: Amgen (industry)
Eligibility: age 18 to 65; BMI 30 to 40; HbA1c at most 6.5 or fasting glucose below 125 mg/dL

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: full analysis
Missing data: none

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Placebo SAD placebo SC (pooled cohorts)	lifestyle: not reported	12	12
A10	Maridebart cafraglutide 280 mg injection every 4 weeks AMG 133 280 mg Q4W	lifestyle: not reported		6	6
A11	Maridebart cafraglutide 420 mg injection every 4 weeks AMG 133 420 mg Q4W	lifestyle: not reported		8	4
A12	maridebart cafraglutide AMG 133 70 mg IV single dose (cohort 6)	lifestyle: not reported		6
A13	Placebo IV placebo single dose (cohort 6)	lifestyle: not reported		2
A14	maridebart cafraglutide AMG 133 280 mg Q4W (cohort 10)	lifestyle: not reported		10
A15	Placebo Placebo Q4W (cohort 10)	lifestyle: not reported		3
A2	maridebart cafraglutide AMG 133 21 mg single dose	lifestyle: not reported		6
A3	maridebart cafraglutide AMG 133 70 mg single dose	lifestyle: not reported		6
A4	maridebart cafraglutide AMG 133 140 mg single dose	lifestyle: not reported		7
A5	maridebart cafraglutide AMG 133 280 mg single dose	lifestyle: not reported		6
A6	maridebart cafraglutide AMG 133 560 mg single dose	lifestyle: not reported		6
A7	maridebart cafraglutide AMG 133 840 mg single dose	lifestyle: not reported		6
A8	Placebo MAD placebo Q4W (cohorts 7 to 9)	lifestyle: not reported		6	6
A9	Maridebart cafraglutide 140 mg injection every 4 weeks AMG 133 140 mg Q4W	lifestyle: not reported		6	6

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	AMG 133 21 mg single dose A2	AMG 133 70 mg single dose A3	AMG 133 140 mg single dose A4	AMG 133 280 mg single dose A5	AMG 133 560 mg single dose A6	AMG 133 840 mg single dose A7	Placebo A8	Maridebart cafraglutide 140 mg injection every 4 weeks A9	Maridebart cafraglutide 280 mg injection every 4 weeks A10	Maridebart cafraglutide 420 mg injection every 4 weeks A11	AMG 133 70 mg IV single dose (cohort 6) A12	Placebo A13	AMG 133 280 mg Q4W (cohort 10) A14	Placebo A15
age	mean (years)	45.7	53.8	47.8	48.0	45.5	50.2	45.7	45.7	40.3	44.5	51.6
age	sd (years)	13.4	9.5	12.9	11.9	11.6	7.2	13.7	14.0	16.6	13.8	12.8
asian	n	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0
asian	percent	0.0	0.0	0.0	0.0	0.0	0.0	16.7	0.0	16.7	0.0	0.0
black	n	4	2	2	5	3	0	0	1	3	1	1	5	0	0	0
black	percent	33.3	33.3	33.3	71.4	50.0	0.0	0.0	16.7	50.0	16.7	12.5
bmi	mean (kg/m2)	32.8	33.8	32.5	33.9	34.8	34.3	32.5	34.2	34.1	33.4	32.5
bmi	sd (kg/m2)	2.1	2.6	4.0	1.8	4.0	3.6	2.3	3.7	2.9	3.6	2.6
female	n	4	5	1	3	2	1	1	4	1	2	7	2	0	5	1
hba1c	mean (percent)	5.38	5.62	5.45	5.61	5.40	5.48	5.57	5.50	5.60	5.57	5.58
hba1c	sd (percent)	0.35	0.22	0.41	0.48	0.74	0.26	0.27	0.20	0.48	0.33	0.27
hispanic	n	5	1	2	1	1	0	5	2	2	4	4	0	2	10	3
other male	n	8	1	5	4	4	5	5	2	5	4	1
other male	percent	66.7	16.7	83.3	57.1	66.7	83.3	83.3	33.3	83.3	66.7	12.5
other race american indian alaska native	n	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
other race american indian alaska native	percent	0.0	0.0	0.0	0.0	0.0	16.7	0.0	0.0	0.0	0.0	0.0
waist	mean (cm)								108.1	105.2	106.2	102.4
waist	sd (cm)								16.7	10.0	20.9	10.8
weight	mean (kg)	97.2	94.9	104.5	95.5	101.4	107.4	98.8	98.9	101.5	98.7	90.5
weight	sd (kg)	12.4	11.0	13.0	14.5	9.7	21.0	13.5	15.8	8.3	16.5	10.3
white	n	8	4	4	2	3	5	5	5	2	5	7	1	2	10	3
white	percent	66.7	66.7	66.7	28.6	50.0	83.3	83.3	83.3	33.3	83.3	87.5

Analyses this trial contributes to

Results

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

Percent body weight change (5 lines; O10)

Week	Arm	Statistic	Estimate	Detail
4	A1	percent change	0.2 percent	not stated; full analysis; R0006305:Results
4	A2	percent change	-2.4 percent	not stated; full analysis; R0006305:Results
12	A11	percent change	-14.5 percent	not stated; full analysis; R0006305:Results
12	A8	percent change	1.5 percent	not stated; full analysis; R0006305:Results
29.43	A11	percent change	-11.2 percent	not stated; full analysis; R0006305:Results

All cause mortality (15 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 12	not stated; safety; registry:adverse_events
A10	events	0 / 6	not stated; safety; registry:adverse_events
A11	events	0 / 8	not stated; safety; registry:adverse_events
A12	events	0 / 6	not stated; safety; registry:adverse_events
A13	events	0 / 2	not stated; safety; registry:adverse_events
A14	events	0 / 10	not stated; safety; registry:adverse_events
A15	events	0 / 3	not stated; safety; registry:adverse_events
A2	events	0 / 6	not stated; safety; registry:adverse_events
A3	events	0 / 6	not stated; safety; registry:adverse_events
A4	events	0 / 7	not stated; safety; registry:adverse_events
A5	events	0 / 6	not stated; safety; registry:adverse_events
A6	events	0 / 6	not stated; safety; registry:adverse_events
A7	events	0 / 6	not stated; safety; registry:adverse_events
A8	events	0 / 6	not stated; safety; registry:adverse_events
A9	events	0 / 6	not stated; safety; registry:adverse_events

Serious adverse events (15 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	0 / 12	not stated; safety; R0006305:Results
A10	events	0 / 6	not stated; safety; R0006305:Results
A11	events	0 / 8	not stated; safety; R0006305:Results
A12	events	0 / 6	not stated; safety; registry:adverse_events
A13	events	0 / 2	not stated; safety; registry:adverse_events
A14	events	0 / 10	not stated; safety; registry:adverse_events
A15	events	0 / 3	not stated; safety; registry:adverse_events
A2	events	0 / 6	not stated; safety; R0006305:Results
A3	events	0 / 6	not stated; safety; R0006305:Results
A4	events	0 / 7	not stated; safety; R0006305:Results
A5	events	0 / 6	not stated; safety; R0006305:Results
A6	events	0 / 6	not stated; safety; R0006305:Results
A7	events	0 / 6	not stated; safety; R0006305:Results
A8	events	0 / 6	not stated; safety; R0006305:Results
A9	events	0 / 6	not stated; safety; R0006305:Results

Discontinuation due to adverse events (11 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 12	not stated; safety; R0006305:Results
A10	events	0 / 6	not stated; safety; R0006305:Results
A11	events	0 / 8	not stated; safety; R0006305:Results
A2	events	0 / 6	not stated; safety; R0006305:Results
A3	events	0 / 6	not stated; safety; R0006305:Results
A4	events	0 / 7	not stated; safety; R0006305:Results
A5	events	0 / 6	not stated; safety; R0006305:Results
A6	events	0 / 6	not stated; safety; R0006305:Results
A7	events	0 / 6	not stated; safety; R0006305:Results
A8	events	0 / 6	not stated; safety; R0006305:Results
A9	events	0 / 6	not stated; safety; R0006305:Results

Nausea (15 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	3 / 12	not stated; safety; R0006305:Table 2
A10	events	4 / 6	not stated; safety; R0006305:Table 2
A11	events	8 / 8	not stated; safety; R0006305:Table 2
A12	events	6 / 6	not stated; safety; registry:adverse_events
A13	events	0 / 2	not stated; safety; registry:adverse_events
A14	events	3 / 10	not stated; safety; registry:adverse_events
A15	events	0 / 3	not stated; safety; registry:adverse_events
A2	events	0 / 6	not stated; safety; R0006305:Table 2
A3	events	2 / 6	not stated; safety; R0006305:Table 2
A4	events	4 / 7	not stated; safety; R0006305:Table 2
A5	events	4 / 6	not stated; safety; R0006305:Table 2
A6	events	5 / 6	not stated; safety; R0006305:Table 2
A7	events	5 / 6	not stated; safety; R0006305:Table 2
A8	events	1 / 6	not stated; safety; R0006305:Table 2
A9	events	5 / 6	not stated; safety; R0006305:Table 2

Vomiting (15 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 12	not stated; safety; R0006305:Table 2
A10	events	5 / 6	not stated; safety; R0006305:Table 2
A11	events	6 / 8	not stated; safety; R0006305:Table 2
A12	events	2 / 6	not stated; safety; registry:adverse_events
A13	events	0 / 2	not stated; safety; registry:adverse_events
A14	events	7 / 10	not stated; safety; registry:adverse_events
A15	events	0 / 3	not stated; safety; registry:adverse_events
A2	events	0 / 6	not stated; safety; R0006305:Table 2
A3	events	1 / 6	not stated; safety; R0006305:Table 2
A4	events	4 / 7	not stated; safety; R0006305:Table 2
A5	events	5 / 6	not stated; safety; R0006305:Table 2
A6	events	5 / 6	not stated; safety; R0006305:Table 2
A7	events	4 / 6	not stated; safety; R0006305:Table 2
A8	events	0 / 6	not stated; safety; R0006305:Table 2
A9	events	4 / 6	not stated; safety; R0006305:Table 2

Diarrhea (15 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	2 / 12	not stated; safety; R0006305:Table 2
A10	events	0 / 6	not stated; safety; R0006305:Table 2
A11	events	2 / 8	not stated; safety; R0006305:Table 2
A12	events	0 / 6	not stated; safety; registry:adverse_events
A13	events	0 / 2	not stated; safety; registry:adverse_events
A14	events	2 / 10	not stated; safety; registry:adverse_events
A15	events	0 / 3	not stated; safety; registry:adverse_events
A2	events	0 / 6	not stated; safety; R0006305:Table 2
A3	events	0 / 6	not stated; safety; R0006305:Table 2
A4	events	0 / 7	not stated; safety; R0006305:Table 2
A5	events	0 / 6	not stated; safety; R0006305:Table 2
A6	events	0 / 6	not stated; safety; R0006305:Table 2
A7	events	0 / 6	not stated; safety; R0006305:Table 2
A8	events	0 / 6	not stated; safety; R0006305:Table 2
A9	events	1 / 6	not stated; safety; R0006305:Table 2

Constipation (15 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	1 / 12	not stated; safety; R0006305:Table 2
A10	events	1 / 6	not stated; safety; R0006305:Table 2
A11	events	0 / 8	not stated; safety; R0006305:Table 2
A12	events	3 / 6	not stated; safety; registry:adverse_events
A13	events	0 / 2	not stated; safety; registry:adverse_events
A14	events	0 / 10	not stated; safety; registry:adverse_events
A15	events	0 / 3	not stated; safety; registry:adverse_events
A2	events	0 / 6	not stated; safety; R0006305:Table 2
A3	events	0 / 6	not stated; safety; R0006305:Table 2
A4	events	0 / 7	not stated; safety; R0006305:Table 2
A5	events	1 / 6	not stated; safety; R0006305:Table 2
A6	events	0 / 6	not stated; safety; R0006305:Table 2
A7	events	3 / 6	not stated; safety; R0006305:Table 2
A8	events	0 / 6	not stated; safety; R0006305:Table 2
A9	events	2 / 6	not stated; safety; R0006305:Table 2