parallel randomized trial

NCT00299871

A 13-week Multinational, Randomized, Double-Blind, Placebo-Controlled, Dose-Response Trial Assessing the Safety, Tolerability and Efficacy of AVE0010 in Metformin-Treated Subjects With Type 2 Diabetes Mellitus

Type 2 diabetes (adults)NCT00299871S001455

Design

Randomized: 542
Start year: 2006
Treatment: 13 weeks, follow-up 13 weeks
Countries: Brazil, Canada, Poland, Romania, Russian Federation, Ukraine, USA (133 sites)
Sponsor: sanofi-aventis (industry)
Eligibility: age 30 to 75; HbA1c 7.0 to below 9.0 percent on metformin at least 1000 mg/day

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: modified itt
Missing data

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Placebo Placebo pooled	metformin at least 1000 mg/day; lifestyle: standard	109	108	103
A2	Lixisenatide 5 µg injection once daily Lixisenatide 5 ug QD	metformin at least 1000 mg/day; lifestyle: standard	55	55	53
A3	Lixisenatide 10 µg injection once daily Lixisenatide 10 ug QD	metformin at least 1000 mg/day; lifestyle: standard	52	51	47
A4	Lixisenatide 20 ug subcutaneous once daily Lixisenatide 20 ug QD	metformin at least 1000 mg/day; lifestyle: standard	55	53	46
A5	Lixisenatide 30 µg injection once daily Lixisenatide 30 ug QD	metformin at least 1000 mg/day; lifestyle: standard	54	52	45
A6	Lixisenatide 5 µg injection twice daily Lixisenatide 5 ug BID	metformin at least 1000 mg/day; lifestyle: standard	53	51	51
A7	Lixisenatide 10 µg injection twice daily Lixisenatide 10 ug BID	metformin at least 1000 mg/day; lifestyle: standard	56	54	51
A8	Lixisenatide 20 µg injection twice daily Lixisenatide 20 ug BID	metformin at least 1000 mg/day; lifestyle: standard	54	52	46
A9	Lixisenatide 30 µg injection twice daily Lixisenatide 30 ug BID	metformin at least 1000 mg/day; lifestyle: standard	54	53	47

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	Lixisenatide 5 µg injection once daily A2	Lixisenatide 10 µg injection once daily A3	Lixisenatide 20 ug subcutaneous once daily A4	Lixisenatide 30 µg injection once daily A5	Lixisenatide 5 µg injection twice daily A6	Lixisenatide 10 µg injection twice daily A7	Lixisenatide 20 µg injection twice daily A8	Lixisenatide 30 µg injection twice daily A9
age	mean (years)	56.3	56.8	55.4	55.4	56.5	57.1	56.0	56.7	55.3
age	sd (years)	9.2	7.8	9.2	9.9	8.7	8.2	7.9	8.3	9.1
black	n	12	5	6	1	6	2	2	2	9
black	percent	11.0	9.1	11.5	1.8	11.1	3.8	3.6	3.7	16.7
bmi	mean (kg/m2)	31.7	30.7	31.9	32.0	31.6	31.6	32.8	32.7	32.3
bmi	sd (kg/m2)	4.2	4.6	4.0	4.3	3.6	4.2	4.4	4.4	4.5
diabetes duration	mean (years)	7.1	7.2	6.2	6.4	6.0	6.2	6.4	6.6	7.0
diabetes duration	sd (years)	5.4	4.9	4.1	6.8	4.8	6.0	5.0	5.1	5.4
hba1c	mean (percent)	7.53	7.58	7.52	7.58	7.52	7.60	7.54	7.61	7.46
hba1c	sd (percent)	0.6	0.7	0.6	0.7	0.7	0.6	0.6	0.7	0.5
other male	n	61	26	31	28	27	25	29	20	23
other male	percent	56.0	47.3	59.6	50.9	50.0	47.2	51.8	37.0	42.6
other race other	n	13	12	10	9	5	5	9	10	10
other race other	percent	11.9	21.8	19.3	16.4	9.3	9.4	16.0	18.5	18.5
weight	mean (kg)	87.7	84.6	90.5	89.4	87.6	86.5	89.8	88.5	87.5
weight	sd (kg)	14	16	17	17	15	14	17	17	14
white	n	84	38	36	45	43	46	45	42	35
white	percent	77.1	69.1	69.2	81.8	79.6	86.8	80.4	77.8	64.8

Analyses this trial contributes to

Results

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

HbA1c change (9 lines; O01)

Week	Arm	Statistic	Estimate	Detail
13	A1	change	-0.18 percent	not stated; modified itt; R0021613:Results
13	A2	change	-0.47 percent	not stated; modified itt; R0021613:Results
13	A3	change	-0.50 percent	not stated; modified itt; R0021613:Results
13	A4	change	-0.69 percent	not stated; modified itt; R0021613:Results
13	A5	change	-0.76 percent	not stated; modified itt; R0021613:Results
13	A6	change	-0.65 percent	not stated; modified itt; R0021613:Results
13	A7	change	-0.78 percent	not stated; modified itt; R0021613:Results
13	A8	change	-0.75 percent	not stated; modified itt; R0021613:Results
13	A9	change	-0.87 percent	not stated; modified itt; R0021613:Results

Body weight change in kilograms (diabetes) (9 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
13	A1	change	-1.94 kg	0.32	108	not stated; modified itt; R0021613:Table 2
13	A2	change	-2.00 kg	0.40	55	not stated; modified itt; R0021613:Table 2
13	A3	change	-2.39 kg	0.42	51	not stated; modified itt; R0021613:Table 2
13	A4	change	-3.01 kg	0.41	53	not stated; modified itt; R0021613:Table 2
13	A5	change	-3.47 kg	0.41	52	not stated; modified itt; R0021613:Table 2
13	A6	change	-2.10 kg	0.41	51	not stated; modified itt; R0021613:Table 2
13	A7	change	-2.21 kg	0.41	54	not stated; modified itt; R0021613:Table 2
13	A8	change	-2.61 kg	0.41	52	not stated; modified itt; R0021613:Table 2
13	A9	change	-3.89 kg	0.41	53	not stated; modified itt; R0021613:Table 2

HbA1c below 7 percent (1 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
13	A1	responders	32				not stated; modified itt; R0021613:Results

Level 2 or 3 hypoglycemia (participants) (18 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 109	while on treatment; safety; R0021613:Results
A1	events	1 / 109	while on treatment; safety; R0021613:Table 3
A2	events	1 / 55	while on treatment; safety; R0021613:Table 3
A2	events	0 / 55	while on treatment; safety; R0021613:Results
A3	events	0 / 52	while on treatment; safety; R0021613:Results
A3	events	2 / 52	while on treatment; safety; R0021613:Table 3
A4	events	1 / 55	while on treatment; safety; R0021613:Table 3
A4	events	0 / 55	while on treatment; safety; R0021613:Results
A5	events	0 / 54	while on treatment; safety; R0021613:Results
A5	events	1 / 54	while on treatment; safety; R0021613:Table 3
A6	events	3 / 53	while on treatment; safety; R0021613:Table 3
A6	events	0 / 53	while on treatment; safety; R0021613:Results
A7	events	1 / 56	while on treatment; safety; R0021613:Table 3
A7	events	0 / 56	while on treatment; safety; R0021613:Results
A8	events	0 / 54	while on treatment; safety; R0021613:Results
A8	events	3 / 54	while on treatment; safety; R0021613:Table 3
A9	events	0 / 54	while on treatment; safety; R0021613:Results
A9	events	1 / 54	while on treatment; safety; R0021613:Table 3

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A2	events	0 / 55	while on treatment; safety; R0021613:Table 3
A6	events	0 / 53	while on treatment; safety; R0021613:Table 3
A9	events	0 / 54	while on treatment; safety; R0021613:Table 3

Hospitalization for heart failure (3 lines; O23)

Arm	Statistic	Events / N	Detail
A2	events	0 / 55	while on treatment; safety; R0021613:Table 3
A6	events	0 / 53	while on treatment; safety; R0021613:Table 3
A9	events	0 / 54	while on treatment; safety; R0021613:Table 3

Serious adverse events (9 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	3 / 109	while on treatment; safety; R0021613:Table 3
A2	events	0 / 55	while on treatment; safety; R0021613:Table 3
A3	events	1 / 52	while on treatment; safety; R0021613:Table 3
A4	events	1 / 55	while on treatment; safety; R0021613:Table 3
A5	events	3 / 54	while on treatment; safety; R0021613:Table 3
A6	events	0 / 53	while on treatment; safety; R0021613:Table 3
A7	events	1 / 56	while on treatment; safety; R0021613:Table 3
A8	events	2 / 54	while on treatment; safety; R0021613:Table 3
A9	events	0 / 54	while on treatment; safety; R0021613:Table 3

Discontinuation due to adverse events (9 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	2 / 109	not stated; safety; R0021613:Table 1
A2	events	1 / 55	not stated; safety; R0021613:Table 1
A3	events	2 / 52	not stated; safety; R0021613:Table 1
A4	events	3 / 55	not stated; safety; R0021613:Table 1
A5	events	6 / 54	not stated; safety; R0021613:Table 1
A6	events	0 / 53	not stated; safety; R0021613:Table 1
A7	events	2 / 56	not stated; safety; R0021613:Table 1
A8	events	8 / 54	not stated; safety; R0021613:Table 1
A9	events	5 / 54	not stated; safety; R0021613:Table 1

Nausea (9 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	5 / 109	while on treatment; safety; R0021613:Table 3
A2	events	4 / 55	while on treatment; safety; R0021613:Table 3
A3	events	6 / 52	while on treatment; safety; R0021613:Table 3
A4	events	14 / 55	while on treatment; safety; R0021613:Table 3
A5	events	19 / 54	while on treatment; safety; R0021613:Table 3
A6	events	4 / 53	while on treatment; safety; R0021613:Table 3
A7	events	8 / 56	while on treatment; safety; R0021613:Table 3
A8	events	12 / 54	while on treatment; safety; R0021613:Table 3
A9	events	18 / 54	while on treatment; safety; R0021613:Table 3

Vomiting (9 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 109	while on treatment; safety; R0021613:Table 3
A2	events	2 / 55	while on treatment; safety; R0021613:Table 3
A3	events	3 / 52	while on treatment; safety; R0021613:Table 3
A4	events	3 / 55	while on treatment; safety; R0021613:Table 3
A5	events	10 / 54	while on treatment; safety; R0021613:Table 3
A6	events	3 / 53	while on treatment; safety; R0021613:Table 3
A7	events	4 / 56	while on treatment; safety; R0021613:Table 3
A8	events	5 / 54	while on treatment; safety; R0021613:Table 3
A9	events	2 / 54	while on treatment; safety; R0021613:Table 3

Diarrhea (9 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	8 / 109	while on treatment; safety; R0021613:Table 3
A2	events	3 / 55	while on treatment; safety; R0021613:Table 3
A3	events	4 / 52	while on treatment; safety; R0021613:Table 3
A4	events	5 / 55	while on treatment; safety; R0021613:Table 3
A5	events	4 / 54	while on treatment; safety; R0021613:Table 3
A6	events	3 / 53	while on treatment; safety; R0021613:Table 3
A7	events	4 / 56	while on treatment; safety; R0021613:Table 3
A8	events	6 / 54	while on treatment; safety; R0021613:Table 3
A9	events	14 / 54	while on treatment; safety; R0021613:Table 3

Acute pancreatitis (9 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 109	while on treatment; safety; R0021613:Results
A2	events	0 / 55	while on treatment; safety; R0021613:Results
A3	events	0 / 52	while on treatment; safety; R0021613:Results
A4	events	0 / 55	while on treatment; safety; R0021613:Results
A5	events	0 / 54	while on treatment; safety; R0021613:Results
A6	events	0 / 53	while on treatment; safety; R0021613:Results
A7	events	0 / 56	while on treatment; safety; R0021613:Results
A8	events	0 / 54	while on treatment; safety; R0021613:Results
A9	events	0 / 54	while on treatment; safety; R0021613:Results

Death by suicide (3 lines; O35B)

Arm	Statistic	Events / N	Detail
A2	events	0 / 55	while on treatment; safety; R0021613:Table 3
A6	events	0 / 53	while on treatment; safety; R0021613:Table 3
A9	events	0 / 54	while on treatment; safety; R0021613:Table 3