parallel randomized trial

NCT02229383

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Once Weekly Exenatide Therapy Added to Titrated Basal Insulin Glargine Compared to Placebo Added to Titrated Basal Insulin Glargine in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Glargine With or Without Metformin

Type 2 diabetes (adults)NCT02229383S000703

Design

Randomized: 464
Start year: 2014
Treatment: 28 weeks, follow-up 38 weeks
Countries: Hungary, Poland, Romania, Slovakia, South Africa, United States (126 sites)
Sponsor: AstraZeneca (industry)
Eligibility: adults; insulin glargine 20 U/d or more with or without metformin; HbA1c 7.0 to 10.5 percent at randomization

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: hypothetical
Analysis population: modified itt
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Exenatide extended release 2 mg subcutaneous once weekly Exenatide QW 2 mg plus insulin glargine	titrated insulin glargine with or without metformin; lifestyle: standard	233	231	211
A2	Placebo Placebo plus insulin glargine	titrated insulin glargine with or without metformin; lifestyle: standard	231	230	207

Baseline characteristics

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

Characteristic	Statistic	Exenatide extended release 2 mg subcutaneous once weekly A1	Placebo A2
age: 65 or older	n	50	58
age: 65 or older	percent	21.6	25.2
age	mean (years)	57.8	57.6
age	sd (years)	9.0	10.3
asian	n	4	2
asian	percent	1.7	0.9
black	n	19	28
black	percent	8.2	12.2
bmi	mean (kg/m2)	33.3	34.1
bmi	sd (kg/m2)	6.1	6.6
diabetes duration	mean (years)	11.5	11.1
diabetes duration	sd (years)	6.6	6.1
egfr	mean (mL/min/1.73 m2)	90.7	91.1
egfr	sd (mL/min/1.73 m2)	17.8	19.2
hba1c	mean (percent)	8.53	8.53
hba1c	sd (percent)	0.91	0.92
hispanic	n	65	65
hispanic	percent	28.1	28.3
insulin dose	mean (U/day)	50.1	52.0
insulin dose	sd (U/day)	21.4	25.0
other background metformin alone	n	121	117
other background metformin alone	percent	52.4	50.9
other background metformin prior su	n	73	70
other background metformin prior su	percent	31.6	30.4
other background none	n	29	33
other background none	percent	12.6	14.3
other background prior su alone	n	8	10
other background prior su alone	percent	3.5	4.3
other male	n	114	107
other male	percent	49.4	46.5
other race other	n	3	4
other race other	percent	1.3	1.7
weight	mean (kg)	93.3	94.7
weight	sd (kg)	20.0	19.8
white	n	205	196
white	percent	88.7	85.2

Analyses this trial contributes to

Results

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

HbA1c change (3 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
28	A1 vs A2	md	-0.73 percent		-0.93 to -0.53		hypothetical; modified itt; R0014763:Table 2
28	A1	change	-0.96 percent	0.08		231	hypothetical; modified itt; R0014763:Table 2
28	A2	change	-0.23 percent	0.08		230	hypothetical; modified itt; R0014763:Table 2

Body weight change in kilograms (diabetes) (3 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
28	A1	change	-1.04 kg	0.26		231	hypothetical; modified itt; R0014763:Table 2
28	A1 vs A2	md	-1.50 kg		-2.17 to -0.84		hypothetical; modified itt; R0014763:Table 2
28	A2	change	0.46 kg	0.25		230	hypothetical; modified itt; R0014763:Table 2

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	Events / N	Detail
28	A1	responders		75 / 231	hypothetical; modified itt; R0014763:Table 2
28	A1 vs A2	rd	25.1		hypothetical; modified itt; R0014763:Table 2
28	A2	responders		17 / 230	hypothetical; modified itt; R0014763:Table 2

Level 2 or 3 hypoglycemia (participants) (4 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 232	not stated; safety; R0014763:Table 3
A1	events	13 / 232	not stated; safety; R0014763:Table 3
A2	events	13 / 231	not stated; safety; R0014763:Table 3
A2	events	0 / 231	not stated; safety; R0014763:Table 3

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
28	A1	change	-2.6 mmHg	0.9		231	hypothetical; modified itt; R0014763:Table 2
28	A1 vs A2	md	-1.8 mmHg		-4.0 to 0.4		hypothetical; modified itt; R0014763:Table 2
28	A2	change	-0.7 mmHg	0.9		230	hypothetical; modified itt; R0014763:Table 2

Weight loss of 5 percent or more (3 lines; O11A)

Week	Arm	Statistic	Estimate	Events / N	Detail
28	A1	responders		24 / 231	hypothetical; modified itt; R0014763:Table 2
28	A1 vs A2	rd	6.9		hypothetical; modified itt; R0014763:Table 2
28	A2	responders		8 / 230	hypothetical; modified itt; R0014763:Table 2

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 232	not stated; safety; R0014763:Table 3
	A2	events				0 / 231	not stated; safety; R0014763:Table 3

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 232	not stated; safety; R0014763:Table 3
	A2	events				1 / 231	not stated; safety; R0014763:Table 3

Health related quality of life total score (any instrument) (3 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
28	A1	change	1.48 points	0.43		231	hypothetical; modified itt; R0014763:Supplement Table S7
28	A1 vs A2	md	1.03 points		0.19 to 1.88		hypothetical; modified itt; R0014763:Supplement Table S7
28	A2	change	0.45 points	0.43		230	hypothetical; modified itt; R0014763:Supplement Table S7

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				11 / 232	not stated; safety; R0014763:Table 3
	A2	events				11 / 231	not stated; safety; R0014763:Table 3

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	9 / 232	not stated; safety; R0014763:Figure 1
A1	events	7 / 232	not stated; safety; R0014763:Table 3
A2	events	4 / 231	not stated; safety; R0014763:Figure 1
A2	events	5 / 231	not stated; safety; R0014763:Table 3

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				12 / 232	not stated; safety; R0014763:Table 3
	A2	events				9 / 231	not stated; safety; R0014763:Table 3

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 232	not stated; safety; R0014763:Table 3
	A2	events				3 / 231	not stated; safety; R0014763:Table 3

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				11 / 232	not stated; safety; R0014763:Table 3
	A2	events				8 / 231	not stated; safety; R0014763:Table 3

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 232	not stated; safety; R0014763:Table 3
	A2	events				4 / 231	not stated; safety; R0014763:Table 3

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 232	not stated; safety; R0014763:Table 3
	A2	events				0 / 231	not stated; safety; R0014763:Table 3

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				4 / 232	not stated; safety; R0014763:Table 3
	A2	events				2 / 231	not stated; safety; R0014763:Table 3