parallel randomized trial

NCT02759107

A Single- and Multiple-Ascending Dose Study in Healthy Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3298176 and Multiple Doses in Patients With Type 2 Diabetes Mellitus

Type 2 diabetes (adults)Other conditions NCT02759107S000482

Design

Randomized
Start year: 2016
Treatment: 4 weeks, follow-up 8 weeks
Countries: United States, Singapore (2 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: POC part: T2D age 21 to 70, BMI 25 or higher, HbA1c 7.0 to 11.0 percent, diet or one oral drug; healthy parts BMI 18.5 to 40

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: yes
Primary estimand: not stated
Analysis population: safety
Missing data

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	tirzepatide Part A tirzepatide 0.25 mg single dose	lifestyle: not reported	6	6
A10	tirzepatide Part B tirzepatide 4.5 mg weekly	lifestyle: not reported	6	6
A11	Tirzepatide 10 mg subcutaneous once weekly Part B tirzepatide 5/5/8/10 mg weekly	lifestyle: not reported	7	7
A12	Dulaglutide 1.5 mg subcutaneous once weekly Part B dulaglutide 1.5 mg weekly	lifestyle: not reported	4	4
A13	Placebo Part B placebo weekly	lifestyle: not reported	4	4
A14	tirzepatide Part C tirzepatide 0.5 mg weekly	diet and exercise or metformin; lifestyle: not reported	9	9
A15	Tirzepatide 5 mg subcutaneous once weekly Part C tirzepatide 5 mg weekly	diet and exercise or metformin; lifestyle: not reported	9	9
A16	Tirzepatide 10 mg subcutaneous once weekly Part C tirzepatide 5/5/10/10 mg weekly	diet and exercise or metformin; lifestyle: not reported	12	12
A17	Tirzepatide 15 mg subcutaneous once weekly Part C tirzepatide 5/5/10/15 mg weekly	diet and exercise or metformin; lifestyle: not reported	12	12
A18	Placebo Part C placebo weekly	diet and exercise or metformin; lifestyle: not reported	11	11
A2	tirzepatide Part A tirzepatide 0.5 mg single dose	lifestyle: not reported	12	12
A3	tirzepatide Part A tirzepatide 1 mg single dose	lifestyle: not reported	5	5
A4	tirzepatide Part A tirzepatide 2.5 mg single dose	lifestyle: not reported	6	6
A5	tirzepatide Part A tirzepatide 5 mg single dose	lifestyle: not reported	6	6
A6	tirzepatide Part A tirzepatide 8 mg single dose	lifestyle: not reported	7	7
A7	Placebo Part A placebo single dose	lifestyle: not reported	14	14
A8	tirzepatide Part B tirzepatide 0.5 mg weekly	lifestyle: not reported	6	6
A9	tirzepatide Part B tirzepatide 1.5 mg weekly	lifestyle: not reported	6	6

Baseline characteristics

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

Characteristic	Statistic	Part A tirzepatide 0.25 mg single dose A1	Part A tirzepatide 0.5 mg single dose A2	Part A tirzepatide 1 mg single dose A3	Part A tirzepatide 2.5 mg single dose A4	Part A tirzepatide 5 mg single dose A5	Part A tirzepatide 8 mg single dose A6	Placebo A7	Part B tirzepatide 0.5 mg weekly A8	Part B tirzepatide 1.5 mg weekly A9	Part B tirzepatide 4.5 mg weekly A10	Tirzepatide 10 mg subcutaneous once weekly A11	Dulaglutide 1.5 mg subcutaneous once weekly A12	Placebo A13	Part C tirzepatide 0.5 mg weekly A14	Tirzepatide 5 mg subcutaneous once weekly A15	Tirzepatide 10 mg subcutaneous once weekly A16	Tirzepatide 15 mg subcutaneous once weekly A17	Placebo A18	Whole trial ALL
age: 65 or older	n	0	0	1	0	0	0	0	0	0	0	0	0	0	2	1	0	1	4
age part:mad	mean (years)																			40.3
age part:mad	sd (years)																			10.9
age part:poc	mean (years)																			56.8
age part:poc	sd (years)																			6.9
age part:sad	mean (years)																			39.4
age part:sad	sd (years)																			10.3
asian	n	6	12	5	6	6	7	13	6	6	5	7	4	4	0	1	5	0	1
black	n	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	2
bmi part:mad	mean (kg/m2)																			24.3
bmi part:mad	sd (kg/m2)																			2.7
bmi part:poc	mean (kg/m2)																			31.2
bmi part:poc	sd (kg/m2)																			4.0
bmi part:sad	mean (kg/m2)																			24.7
bmi part:sad	sd (kg/m2)																			3.2
female	n	1	1	1	0	0	0	0	0	0	6	0	0	0	6	7	2	6	4
hba1c	mean (percent)														7.94	8.43	8.22	8.53	8.75
hba1c	sd (percent)														0.59	0.45	1.00	0.73	0.94
hispanic	n	0	0	0	0	0	0	0	0	0	0	0	0	0	9	8	7	12	10
other race american indian alaska native	n	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
other race multiple	n	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
other race native hawaiian pacific islander	n	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
sbp	mean (mmHg)	115.3	107.3	108.4	114.0	126.3	111.6	113.1	115.7	119.8	116.2	110.9	102.3	116.0	124.4	122.9	128.6	118.8	127.1
sbp	sd (mmHg)	13.5	12.0	4.7	13.4	12.1	6.1	12.3	6.9	17.4	16.3	12.6	1.7	18.2	23.9	13.6	15.2	9.9	24.9
weight part:mad	mean (kg)																			71.1
weight part:mad	sd (kg)																			9.4
weight part:poc	mean (kg)																			86.0
weight part:poc	sd (kg)																			15.9
weight part:sad	mean (kg)																			71.9
weight part:sad	sd (kg)																			11.1
white	n	0	0	0	0	0	0	1	0	0	0	0	0	0	9	7	7	11	7

Results

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

HbA1c change (7 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Detail
4	A14	change	-0.30 percent		not stated; other; R0014066:Supplement Table S3
4	A15	change	-0.46 percent		not stated; other; R0014066:Supplement Table S3
4	A16	change	-1.00 percent		not stated; other; R0014066:Supplement Table S3
4	A16 vs A18	md	-0.84 percent	-1.17 to -0.52	not stated; other; R0014066:Results
4	A17 vs A18	md	-0.58 percent	-0.92 to -0.24	not stated; other; R0014066:Results
4	A17	change	-0.74 percent		not stated; other; R0014066:Supplement Table S3
4	A18	change	-0.16 percent		not stated; other; R0014066:Supplement Table S3

Body weight change in kilograms (diabetes) (7 lines; O02)

Week	Arm	Statistic	Estimate	95% CI	Detail
4	A14	change	-0.70 kg		not stated; other; R0014066:Figure 5A
4	A14 vs A18	md	-0.38 kg	-1.64 to 0.88	not stated; other; R0014066:Supplement Figure S4B
4	A15 vs A18	md	-1.21 kg	-2.54 to 0.11	not stated; other; R0014066:Supplement Figure S4B
4	A15	change	-1.54 kg		not stated; other; R0014066:Figure 5A
4	A16 vs A18	md	-2.62 kg	-3.79 to -1.45	not stated; other; R0014066:Supplement Figure S4B
4	A17 vs A18	md	-2.07 kg	-3.25 to -0.88	not stated; other; R0014066:Supplement Figure S4B
4	A18	change	-0.32 kg		not stated; other; R0014066:Figure 5A

Level 2 or 3 hypoglycemia (participants) (10 lines; O04)

Arm	Statistic	Events / N	Detail
A14	events	0 / 9	not stated; safety; R0014066:Table 3
A14	events	0 / 9	not stated; safety; R0014066:Table 3
A15	events	0 / 9	not stated; safety; R0014066:Table 3
A15	events	0 / 9	not stated; safety; R0014066:Table 3
A16	events	0 / 12	not stated; safety; R0014066:Table 3
A16	events	2 / 12	not stated; safety; R0014066:Table 3
A17	events	0 / 12	not stated; safety; R0014066:Table 3
A17	events	1 / 12	not stated; safety; R0014066:Table 3
A18	events	0 / 11	not stated; safety; R0014066:Table 3
A18	events	1 / 11	not stated; safety; R0014066:Table 3

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	Detail
4	A14	change	4.88 mmHg	not stated; other; R0014066:Supplement Table S5
4	A15	change	-6.61 mmHg	not stated; other; R0014066:Supplement Table S5
4	A16	change	-1.85 mmHg	not stated; other; R0014066:Supplement Table S5
4	A17	change	-5.32 mmHg	not stated; other; R0014066:Supplement Table S5
4	A18	change	5.02 mmHg	not stated; other; R0014066:Supplement Table S5

All cause mortality (5 lines; O20)

Arm	Statistic	Events / N	Detail
A14	events	0 / 9	not stated; safety; R0014066:Results
A15	events	0 / 9	not stated; safety; R0014066:Results
A16	events	0 / 12	not stated; safety; R0014066:Results
A17	events	0 / 12	not stated; safety; R0014066:Results
A18	events	0 / 11	not stated; safety; R0014066:Results

Hospitalization for heart failure (5 lines; O23)

Arm	Statistic	Events / N	Detail
A14	events	0 / 9	not stated; safety; R0014066:Table 3
A15	events	0 / 9	not stated; safety; R0014066:Table 3
A16	events	0 / 12	not stated; safety; R0014066:Table 3
A17	events	0 / 12	not stated; safety; R0014066:Table 3
A18	events	0 / 11	not stated; safety; R0014066:Table 3

Serious adverse events (18 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A10	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A11	events	0 / 7	not stated; safety; R0014066:Supplement Table S4
A12	events	1 / 4	not stated; safety; R0014066:Supplement Table S4
A13	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A14	events	0 / 9	not stated; safety; R0014066:Table 3
A15	events	0 / 9	not stated; safety; R0014066:Table 3
A16	events	0 / 12	not stated; safety; R0014066:Table 3
A17	events	0 / 12	not stated; safety; R0014066:Table 3
A18	events	0 / 11	not stated; safety; R0014066:Table 3
A2	events	0 / 12	not stated; safety; R0014066:Supplement Table S4
A3	events	0 / 5	not stated; safety; R0014066:Supplement Table S4
A4	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A5	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A6	events	0 / 7	not stated; safety; R0014066:Supplement Table S4
A7	events	0 / 14	not stated; safety; R0014066:Supplement Table S4
A8	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A9	events	0 / 6	not stated; safety; R0014066:Supplement Table S4

Discontinuation due to adverse events (25 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A10	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A11	events	1 / 7	not stated; safety; decreased appetite; R0014066:Supplement Figure S5
A11	events	2 / 7	not stated; safety; R0014066:Supplement Table S4
A11	events	1 / 7	not stated; safety; vomiting; R0014066:Supplement Figure S5
A12	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A13	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A14	events	0 / 9	not stated; safety; R0014066:Table 3
A15	events	3 / 9	not stated; safety; R0014066:Table 3
A15	events	1 / 9	not stated; safety; supraventricular tachycardia; R0014066:Supplement Figure S5
A15	events	1 / 9	not stated; randomized; registry:flow
A16	events	0 / 12	not stated; safety; R0014066:Table 3
A17	events	2 / 12	not stated; randomized; registry:flow
A17	events	0 / 12	not stated; safety; R0014066:Table 3
A17	events	1 / 12	not stated; safety; diarrhoea; R0014066:Supplement Figure S5
A17	events	1 / 12	not stated; safety; increased pancreatic enzymes; R0014066:Supplement Figure S5
A18	events	0 / 11	not stated; safety; R0014066:Table 3
A2	events	0 / 12	not stated; safety; R0014066:Supplement Table S4
A3	events	0 / 5	not stated; safety; R0014066:Supplement Table S4
A4	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A5	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A6	events	0 / 7	not stated; safety; R0014066:Supplement Table S4
A7	events	0 / 14	not stated; safety; R0014066:Supplement Table S4
A8	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A9	events	0 / 6	not stated; safety; R0014066:Supplement Table S4

Nausea (18 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A10	events	2 / 6	not stated; safety; R0014066:Supplement Table S4
A11	events	3 / 7	not stated; safety; R0014066:Supplement Table S4
A12	events	1 / 4	not stated; safety; R0014066:Supplement Table S4
A13	events	1 / 4	not stated; safety; R0014066:Supplement Table S4
A14	events	1 / 9	not stated; safety; R0014066:Table 3
A15	events	1 / 9	not stated; safety; R0014066:Table 3
A16	events	1 / 12	not stated; safety; R0014066:Table 3
A17	events	6 / 12	not stated; safety; R0014066:Table 3
A18	events	0 / 11	not stated; safety; R0014066:Table 3
A2	events	0 / 12	not stated; safety; R0014066:Supplement Table S4
A3	events	0 / 5	not stated; safety; R0014066:Supplement Table S4
A4	events	1 / 6	not stated; safety; R0014066:Supplement Table S4
A5	events	1 / 6	not stated; safety; R0014066:Supplement Table S4
A6	events	4 / 7	not stated; safety; R0014066:Supplement Table S4
A7	events	0 / 14	not stated; safety; R0014066:Supplement Table S4
A8	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A9	events	0 / 6	not stated; safety; R0014066:Supplement Table S4

Vomiting (18 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A10	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A11	events	3 / 7	not stated; safety; R0014066:Supplement Table S4
A12	events	1 / 4	not stated; safety; R0014066:Supplement Table S4
A13	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A14	events	1 / 9	not stated; safety; R0014066:Table 3
A15	events	0 / 9	not stated; safety; R0014066:Table 3
A16	events	1 / 12	not stated; safety; R0014066:Table 3
A17	events	9 / 12	not stated; safety; R0014066:Table 3
A18	events	0 / 11	not stated; safety; R0014066:Table 3
A2	events	0 / 12	not stated; safety; R0014066:Supplement Table S4
A3	events	0 / 5	not stated; safety; R0014066:Supplement Table S4
A4	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A5	events	2 / 6	not stated; safety; R0014066:Supplement Table S4
A6	events	3 / 7	not stated; safety; R0014066:Supplement Table S4
A7	events	0 / 14	not stated; safety; R0014066:Supplement Table S4
A8	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A9	events	0 / 6	not stated; safety; R0014066:Supplement Table S4

Diarrhea (18 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; registry:adverse_events
A10	events	1 / 6	not stated; safety; R0014066:Supplement Table S4
A11	events	2 / 7	not stated; safety; R0014066:Supplement Table S4
A12	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A13	events	1 / 4	not stated; safety; R0014066:Supplement Table S4
A14	events	1 / 9	not stated; safety; R0014066:Table 3
A15	events	1 / 9	not stated; safety; R0014066:Table 3
A16	events	3 / 12	not stated; safety; R0014066:Table 3
A17	events	5 / 12	not stated; safety; R0014066:Table 3
A18	events	1 / 11	not stated; safety; R0014066:Table 3
A2	events	0 / 12	not stated; safety; registry:adverse_events
A3	events	0 / 5	not stated; safety; registry:adverse_events
A4	events	0 / 6	not stated; safety; registry:adverse_events
A5	events	0 / 6	not stated; safety; registry:adverse_events
A6	events	0 / 7	not stated; safety; registry:adverse_events
A7	events	0 / 14	not stated; safety; registry:adverse_events
A8	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A9	events	1 / 6	not stated; safety; R0014066:Supplement Table S4

Constipation (18 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; registry:adverse_events
A10	events	0 / 6	not stated; safety; registry:adverse_events
A11	events	0 / 7	not stated; safety; registry:adverse_events
A12	events	0 / 4	not stated; safety; registry:adverse_events
A13	events	0 / 4	not stated; safety; registry:adverse_events
A14	events	0 / 9	not stated; safety; registry:adverse_events
A15	events	0 / 9	not stated; safety; registry:adverse_events
A16	events	1 / 12	not stated; safety; registry:adverse_events
A17	events	2 / 12	not stated; safety; registry:adverse_events
A18	events	0 / 11	not stated; safety; registry:adverse_events
A2	events	0 / 12	not stated; safety; registry:adverse_events
A3	events	0 / 5	not stated; safety; registry:adverse_events
A4	events	0 / 6	not stated; safety; registry:adverse_events
A5	events	0 / 6	not stated; safety; registry:adverse_events
A6	events	0 / 7	not stated; safety; registry:adverse_events
A7	events	0 / 14	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

Discontinuation due to gastrointestinal adverse events (17 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A10	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A11	events	1 / 7	not stated; safety; vomiting; R0014066:Supplement Figure S5
A12	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A13	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A14	events	0 / 9	not stated; safety; R0014066:Table 3
A16	events	0 / 12	not stated; safety; R0014066:Table 3
A17	events	1 / 12	not stated; safety; diarrhoea; R0014066:Supplement Figure S5
A18	events	0 / 11	not stated; safety; R0014066:Table 3
A2	events	0 / 12	not stated; safety; R0014066:Supplement Table S4
A3	events	0 / 5	not stated; safety; R0014066:Supplement Table S4
A4	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A5	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A6	events	0 / 7	not stated; safety; R0014066:Supplement Table S4
A7	events	0 / 14	not stated; safety; R0014066:Supplement Table S4
A8	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A9	events	0 / 6	not stated; safety; R0014066:Supplement Table S4

Acute pancreatitis (18 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A10	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A11	events	0 / 7	not stated; safety; R0014066:Supplement Table S4
A12	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A13	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A14	events	0 / 9	not stated; safety; R0014066:Table 3
A15	events	0 / 9	not stated; safety; R0014066:Table 3
A16	events	0 / 12	not stated; safety; R0014066:Table 3
A17	events	0 / 12	not stated; safety; R0014066:Table 3
A18	events	0 / 11	not stated; safety; R0014066:Table 3
A2	events	0 / 12	not stated; safety; R0014066:Supplement Table S4
A3	events	0 / 5	not stated; safety; R0014066:Supplement Table S4
A4	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A5	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A6	events	0 / 7	not stated; safety; R0014066:Supplement Table S4
A7	events	0 / 14	not stated; safety; R0014066:Supplement Table S4
A8	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A9	events	0 / 6	not stated; safety; R0014066:Supplement Table S4

Death by suicide (18 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6	not stated; safety; R0014066:Results
A10	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A11	events	0 / 7	not stated; safety; R0014066:Supplement Table S4
A12	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A13	events	0 / 4	not stated; safety; R0014066:Supplement Table S4
A14	events	0 / 9	not stated; safety; R0014066:Results
A15	events	0 / 9	not stated; safety; R0014066:Results
A16	events	0 / 12	not stated; safety; R0014066:Results
A17	events	0 / 12	not stated; safety; R0014066:Results
A18	events	0 / 11	not stated; safety; R0014066:Results
A2	events	0 / 12	not stated; safety; R0014066:Results
A3	events	0 / 5	not stated; safety; R0014066:Results
A4	events	0 / 6	not stated; safety; R0014066:Results
A5	events	0 / 6	not stated; safety; R0014066:Results
A6	events	0 / 7	not stated; safety; R0014066:Results
A7	events	0 / 14	not stated; safety; R0014066:Results
A8	events	0 / 6	not stated; safety; R0014066:Supplement Table S4
A9	events	0 / 6	not stated; safety; R0014066:Supplement Table S4