parallel randomized trial

AMPLITUDE-M

A 56-week, Multicenter, Double-blind, Placebo-controlled, Randomized Study to Evaluate the Efficacy and Safety of Efpeglenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise

Type 2 diabetes (adults)NCT03353350S002081

Design

Randomized: 406
Start year: 2017
Treatment: 56 weeks, follow-up 62 weeks
Countries: Germany, Poland, United Kingdom, United States, Ukraine (48 sites)
Sponsor: Sanofi, then Hanmi Pharmaceutical (industry)
Eligibility: type 2 diabetes on diet and exercise, HbA1c 7 to 10 percent, no glucose lowering drug in prior 3 months

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: randomized
Missing data: regression imputation, 10000 imputations

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Efpeglenatide 2 mg subcutaneous once weekly Efpeglenatide 2 mg	diet and exercise; lifestyle: not reported	100	100	78
A2	Efpeglenatide 4 mg subcutaneous once weekly Efpeglenatide 4 mg	diet and exercise; lifestyle: not reported	101	101	73
A3	Efpeglenatide 6 mg subcutaneous once weekly Efpeglenatide 6 mg	diet and exercise; lifestyle: not reported	103	103	67
A4	Placebo Placebo	diet and exercise; lifestyle: not reported	102	102	75

Baseline characteristics

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

Characteristic	Statistic	Efpeglenatide 2 mg subcutaneous once weekly A1	Efpeglenatide 4 mg subcutaneous once weekly A2	Efpeglenatide 6 mg subcutaneous once weekly A3	Placebo A4
age	mean (years)	58.6	56.3	59.6	59.5
age	sd (years)	10.5	11.5	10.7	11.7
asian	n	0	1	2	2
black	n	6	13	8	10
black	percent	6.0	12.9	7.8	9.8
bmi	mean (kg/m2)	34.4	33.8	33.8	34.8
bmi	sd (kg/m2)	6.4	6.6	6.9	7.1
diabetes duration	mean (years)	5.3	4.9	5.2	5.0
diabetes duration	sd (years)	5.3	5.0	5.2	4.9
egfr	mean (mL/min/1.73 m2)	101.3	106.1	102.3	95.3
egfr	sd (mL/min/1.73 m2)	26.1	29.0	38.8	31.1
female	n	45	49	42	51
female	percent	45.0	48.5	40.8	50.0
hba1c	mean (percent)	8.1	8.1	8.1	8.0
hba1c	sd (percent)	0.9	0.9	1.0	0.9
hispanic	n	20	25	21	20
hispanic	percent	20.0	24.8	20.4	19.6
other race other	n	1	2	3	2
other race other	percent	1.0	2.0	2.9	2.0
weight	mean (kg)	98.0	95.2	96.4	97.9
weight	sd (kg)	21.6	22.7	20.9	22.7
white	n	93	86	92	90
white	percent	93.0	85.1	89.3	88.2

Analyses this trial contributes to

Results

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

HbA1c change (22 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-1.1 percent	0.1		100	not stated; randomized; R0007136:Results
30	A1	change	-1.14 percent	0.96		100	not stated; randomized; registry:outcomes
30	A1 vs A4	md	-0.5 percent		-0.9 to -0.2		not stated; randomized; R0007136:Results
30	A2	change	-1.48 percent	1.01		101	not stated; randomized; registry:outcomes
30	A2 vs A4	md	-0.8 percent		-1.2 to -0.5		not stated; randomized; R0007136:Results
30	A2	change	-1.4 percent	0.1		101	not stated; randomized; R0007136:Results
30	A3 vs A4	md	-1.0 percent		-1.4 to -0.7		not stated; randomized; R0007136:Results
30	A3	change	-1.6 percent	0.1		103	not stated; randomized; R0007136:Results
30	A3	change	-1.59 percent	1.04		103	not stated; randomized; registry:outcomes
30	A4	change	-0.46 percent	1.16		102	not stated; randomized; registry:outcomes
30	A4	change	-0.6 percent	1.2		102	not stated; randomized; R0007136:Results
56	A1	change	-1.2 percent	0.2		100	not stated; randomized; R0007136:Results
56	A1 vs A4	md	-0.8 percent		-1.5 to 0.0		not stated; randomized; R0007136:Results
56	A1	change	-1.18 percent	0.79		100	not stated; randomized; registry:outcomes
56	A2	change	-1.3 percent	0.2		101	not stated; randomized; R0007136:Results
56	A2 vs A4	md	-0.9 percent		-1.6 to -0.1		not stated; randomized; R0007136:Results
56	A2	change	-1.51 percent	0.99		101	not stated; randomized; registry:outcomes
56	A3	change	-1.3 percent	0.2		103	not stated; randomized; R0007136:Results
56	A3 vs A4	md	-0.9 percent		-1.6 to -0.2		not stated; randomized; R0007136:Results
56	A3	change	-1.51 percent	0.18		103	not stated; randomized; registry:outcomes
56	A4	change	-0.52 percent	1.18		102	not stated; randomized; registry:outcomes
56	A4	change	-0.4 percent	0.3		102	not stated; randomized; R0007136:Results

Body weight change in kilograms (diabetes) (19 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-0.8 kg	0.5		100	not stated; randomized; R0007136:Figure 2
30	A1	change	-1.01 kg	3.66		100	not stated; randomized; registry:outcomes
30	A2	change	-3.5 kg	0.6		101	not stated; randomized; R0007136:Figure 2
30	A2 vs A4	md	-2.3 kg		-3.9 to -0.7		not stated; randomized; R0007136:Results
30	A2	change	-3.34 kg	4.19		101	not stated; randomized; registry:outcomes
30	A3	change	-3.19 kg	4.77		103	not stated; randomized; registry:outcomes
30	A3	change	-3.4 kg	0.5		103	not stated; randomized; R0007136:Figure 2
30	A3 vs A4	md	-2.2 kg		-3.5 to -0.9		not stated; randomized; R0007136:Results
30	A4	change	-1.2 kg	0.5		102	not stated; randomized; R0007136:Figure 2
30	A4	change	-1.35 kg	3.15		102	not stated; randomized; registry:outcomes
56	A1	change	-1.1 kg	0.9		100	not stated; randomized; R0007136:Figure 2
56	A1	change	-0.94 kg	4.96		100	not stated; randomized; registry:outcomes
56	A2 vs A4	md	-3.6 kg		-6.8 to -0.4		not stated; randomized; R0007136:Results
56	A2	change	-4.7 kg	1.4		101	not stated; randomized; R0007136:Figure 2
56	A2	change	-3.24 kg	6.42		101	not stated; randomized; registry:outcomes
56	A3	change	-1.82 kg	5.52		103	not stated; randomized; registry:outcomes
56	A3	change	-2.2 kg	0.8		103	not stated; randomized; R0007136:Figure 2
56	A4	change	-1.26 kg	4.19		102	not stated; randomized; registry:outcomes
56	A4	change	-1.2 kg	0.8		102	not stated; randomized; R0007136:Figure 2

HbA1c below 7 percent (8 lines; O03)

Week	Arm	Statistic	Estimate	Events / N	Detail
30	A1	responders	60.0	100	not stated; randomized; R0007136:Results
30	A2	responders	65.3	101	not stated; randomized; R0007136:Results
30	A3	responders	73.8	103	not stated; randomized; R0007136:Results
30	A4	responders	25.5	102	not stated; randomized; R0007136:Results
56	A1	responders	54.0	100	not stated; randomized; R0007136:Figure 2
56	A2	responders	57.4	101	not stated; randomized; R0007136:Figure 2
56	A3	responders	57.3	103	not stated; randomized; R0007136:Figure 2
56	A4	responders	23.5	102	not stated; randomized; R0007136:Figure 2

Level 2 or 3 hypoglycemia (participants) (8 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 102	while on treatment; safety; R0007136:Table 2
A1	events	0 / 102	while on treatment; safety; R0007136:Table 2
A2	events	1 / 103	while on treatment; safety; R0007136:Table 2
A2	events	1 / 103	while on treatment; safety; R0007136:Table 2
A3	events	1 / 99	while on treatment; safety; R0007136:Table 2
A3	events	0 / 99	while on treatment; safety; R0007136:Table 2
A4	events	0 / 102	while on treatment; safety; R0007136:Table 2
A4	events	0 / 102	while on treatment; safety; R0007136:Table 2

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 102	not stated; safety; acute kidney injury; registry:adverse_events
A2	events	1 / 103	not stated; safety; acute kidney injury; registry:adverse_events
A3	events	0 / 99	not stated; safety; acute kidney injury; registry:adverse_events
A4	events	0 / 102	not stated; safety; acute kidney injury; registry:adverse_events

All cause mortality (8 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 102	not stated; safety; registry:adverse_events
A1	events	0 / 102	while on treatment; safety; R0007136:Table 2
A2	events	0 / 103	not stated; safety; registry:adverse_events
A2	events	0 / 103	while on treatment; safety; R0007136:Table 2
A3	events	1 / 99	not stated; safety; registry:adverse_events
A3	events	0 / 99	while on treatment; safety; R0007136:Table 2
A4	events	0 / 102	while on treatment; safety; R0007136:Table 2
A4	events	0 / 102	not stated; safety; registry:adverse_events

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	11 / 102	while on treatment; safety; R0007136:Table 2
A2	events	6 / 103	while on treatment; safety; R0007136:Table 2
A3	events	6 / 99	while on treatment; safety; R0007136:Table 2
A4	events	9 / 102	while on treatment; safety; R0007136:Table 2

Discontinuation due to adverse events (12 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	9 / 102	while on treatment; safety; R0007136:Table 2
A1	events	0 / 81	not stated; randomized; registry:flow
A1	events	4 / 100	not stated; randomized; registry:flow
A2	events	2 / 101	not stated; randomized; registry:flow
A2	events	10 / 103	while on treatment; safety; R0007136:Table 2
A2	events	0 / 77	not stated; randomized; registry:flow
A3	events	3 / 103	not stated; randomized; registry:flow
A3	events	17 / 99	while on treatment; safety; R0007136:Table 2
A3	events	1 / 81	not stated; randomized; registry:flow
A4	events	0 / 102	not stated; randomized; registry:flow
A4	events	1 / 80	not stated; randomized; registry:flow
A4	events	5 / 102	while on treatment; safety; R0007136:Table 2

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	6 / 102	while on treatment; safety; R0007136:Table 2
A2	events	15 / 103	while on treatment; safety; R0007136:Table 2
A3	events	22 / 99	while on treatment; safety; R0007136:Table 2
A4	events	2 / 102	while on treatment; safety; R0007136:Table 2

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	3 / 102	while on treatment; safety; R0007136:Table 2
A2	events	8 / 103	while on treatment; safety; R0007136:Table 2
A3	events	9 / 99	while on treatment; safety; R0007136:Table 2
A4	events	0 / 102	while on treatment; safety; R0007136:Table 2

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	9 / 102	while on treatment; safety; R0007136:Table 2
A2	events	17 / 103	while on treatment; safety; R0007136:Table 2
A3	events	25 / 99	while on treatment; safety; R0007136:Table 2
A4	events	9 / 102	while on treatment; safety; R0007136:Table 2

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	9 / 102	while on treatment; safety; R0007136:Table 2
A2	events	14 / 103	while on treatment; safety; R0007136:Table 2
A3	events	16 / 99	while on treatment; safety; R0007136:Table 2
A4	events	6 / 102	while on treatment; safety; R0007136:Table 2

Discontinuation due to gastrointestinal adverse events (4 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	4 / 102	while on treatment; safety; R0007136:Table 2
A2	events	7 / 103	while on treatment; safety; R0007136:Table 2
A3	events	13 / 99	while on treatment; safety; R0007136:Table 2
A4	events	2 / 102	while on treatment; safety; R0007136:Table 2

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 102	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	0 / 102	not stated; safety; R0007136:Results
A2	events	0 / 103	not stated; safety; R0007136:Results
A2	events	1 / 103	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	0 / 99	not stated; safety; R0007136:Results
A3	events	1 / 99	not stated; safety; cholelithiasis; registry:adverse_events
A4	events	1 / 102	not stated; safety; cholelithiasis; registry:adverse_events
A4	events	0 / 102	not stated; safety; R0007136:Results

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 102	not stated; safety; R0007136:Results
A2	events	0 / 103	not stated; safety; R0007136:Results
A3	events	0 / 99	not stated; safety; R0007136:Results
A4	events	0 / 102	not stated; safety; R0007136:Results

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	0 / 102	not stated; safety; diabetic retinopathy; R0007136:Results
A2	events	0 / 103	not stated; safety; diabetic retinopathy; R0007136:Results
A3	events	2 / 99	not stated; safety; diabetic retinopathy; R0007136:Results
A4	events	0 / 102	not stated; safety; diabetic retinopathy; R0007136:Results

Suicidal ideation or behavior (4 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 102	not stated; safety; suicidal ideation; registry:adverse_events
A2	events	0 / 103	not stated; safety; suicidal ideation; registry:adverse_events
A3	events	1 / 99	not stated; safety; suicidal ideation; registry:adverse_events
A4	events	0 / 102	not stated; safety; suicidal ideation; registry:adverse_events