parallel randomized trial

NCT05086445

A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3502970 in Japanese Participants With Type 2 Diabetes Mellitus

Type 2 diabetes (adults)NCT05086445S001999

Design

Randomized: 62
Start year: 2021
Treatment: 12 weeks, follow-up 14 weeks
Countries: Japan (5 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: Japanese; age 20 to 70; BMI 20 to 35; HbA1c 7.0 to 10.0 diet only or 6.5 to 9.0 on one OAM, withdrawn 28 days

Conduct and analysis

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

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Placebo Placebo, pooled across cohorts	none, oral agents withdrawn 28 days before dosing; lifestyle: none	11	11
A2	Orforglipron 12 mg oral once daily Orforglipron 12 mg	none, oral agents withdrawn 28 days before dosing; lifestyle: none	14	14
A3	Orforglipron 24 mg oral once daily Orforglipron 24 mg	none, oral agents withdrawn 28 days before dosing; lifestyle: none	17	17
A4	Orforglipron 45 mg oral once daily Orforglipron 45 mg	none, oral agents withdrawn 28 days before dosing; lifestyle: none	18	18

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	Orforglipron 12 mg oral once daily A2	Orforglipron 24 mg oral once daily A3	Orforglipron 45 mg oral once daily A4
age	mean (years)	57.7	56.3	53.4	57.6
age	sd (years)	5.8	8.6	10.0	6.2
bmi	mean (kg/m2)	27.6	28.3	27.2	26.1
bmi	sd (kg/m2)	3.7	3.3	4.5	4.7
diabetes duration	max (years)	24.0	20.0	17.0	32.0
diabetes duration	mean (years)	9.4	6.1	5.5	8.9
diabetes duration	min (years)	2.0	2.0	2.0	1.0
diabetes duration	sd (years)	6.3	5.5	3.9	7.8
hba1c	mean (percent)	7.8	8.0	7.9	7.8
hba1c	sd (percent)	1.1	0.8	0.7	0.9
other male	n	10	13	17	18
other male	percent	90.9	92.9	100	100
weight	mean (kg)	79.4	82.8	80.8	74.7
weight	sd (kg)	10.1	9.5	15.2	16.3

Analyses this trial contributes to

Results

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

HbA1c change (7 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
12	A1	change	0.67 percent	0.20 to 1.14	10	not stated; modified itt; registry:outcomes
12	A2	change	-2.16 percent	-2.45 to -1.87	12	not stated; modified itt; registry:outcomes
12	A2 vs A1	md	-2.83 percent	-3.38 to -2.28		not stated; modified itt; R0003844:Figure 1b
12	A3	change	-2.17 percent	-2.44 to -1.91	14	not stated; modified itt; registry:outcomes
12	A3 vs A1	md	-2.84 percent	-3.38 to -2.30		not stated; modified itt; R0003844:Figure 1b
12	A4	change	-2.28 percent	-2.52 to -2.04	17	not stated; modified itt; registry:outcomes
12	A4 vs A1	md	-2.95 percent	-3.48 to -2.42		not stated; modified itt; R0003844:Figure 1b

Body weight change in kilograms (diabetes) (14 lines; O02)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
12	A1	change	0.3 kg			not stated; modified itt; R0003844:Results
12	A2 vs A1	md	-2.6 kg	-5.1 to -0.1		not stated; modified itt; R0003844:Figure 1c
12	A2	change	-2.9 kg			not stated; modified itt; R0003844:Results
12	A3 vs A1	md	-5.9 kg	-8.3 to -3.5		not stated; modified itt; R0003844:Figure 1c
12	A3	change	-6.3 kg			not stated; modified itt; R0003844:Results
12	A4 vs A1	md	-4.5 kg	-6.8 to -2.1		not stated; modified itt; R0003844:Figure 1c
12	A4	change	-4.8 kg			not stated; modified itt; R0003844:Results
12.43	A1	change	-0.5 kg	-2.3 to 1.3	10	not stated; modified itt; registry:outcomes
12.43	A2 vs A1	md	-2.9 kg	-5.3 to -0.4		not stated; modified itt; registry:outcomes
12.43	A2	change	-3.4 kg	-5.0 to -1.7	12	not stated; modified itt; registry:outcomes
12.43	A3 vs A1	md	-6.4 kg	-8.7 to -4.0		not stated; modified itt; registry:outcomes
12.43	A3	change	-6.9 kg	-8.4 to -5.4	14	not stated; modified itt; registry:outcomes
12.43	A4	change	-4.9 kg	-6.3 to -3.5	17	not stated; modified itt; registry:outcomes
12.43	A4 vs A1	md	-4.3 kg	-6.6 to -2.1		not stated; modified itt; registry:outcomes

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Table 2
A2	events	0 / 14	not stated; safety; R0003844:Table 2
A3	events	1 / 17	not stated; safety; R0003844:Table 2
A4	events	0 / 18	not stated; safety; R0003844:Table 2

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Table 2
A2	events	0 / 14	not stated; safety; R0003844:Table 2
A3	events	0 / 17	not stated; safety; R0003844:Table 2
A4	events	0 / 18	not stated; safety; R0003844:Table 2

Hospitalization for heart failure (4 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Table 2
A2	events	0 / 14	not stated; safety; R0003844:Table 2
A3	events	0 / 17	not stated; safety; R0003844:Table 2
A4	events	0 / 18	not stated; safety; R0003844:Table 2

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Table 2
A2	events	0 / 14	not stated; safety; R0003844:Table 2
A3	events	0 / 17	not stated; safety; R0003844:Table 2
A4	events	0 / 18	not stated; safety; R0003844:Table 2

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Results
A2	events	1 / 14	not stated; safety; R0003844:Results
A3	events	1 / 17	not stated; safety; R0003844:Results
A4	events	0 / 18	not stated; safety; R0003844:Results

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	2 / 11	not stated; safety; R0003844:Table 2
A2	events	9 / 14	not stated; safety; R0003844:Table 2
A3	events	4 / 17	not stated; safety; R0003844:Table 2
A4	events	6 / 18	not stated; safety; R0003844:Table 2

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 11	not stated; safety; R0003844:Table 2
A2	events	3 / 14	not stated; safety; R0003844:Table 2
A3	events	2 / 17	not stated; safety; R0003844:Table 2
A4	events	1 / 18	not stated; safety; R0003844:Table 2

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	2 / 11	not stated; safety; R0003844:Table 2
A2	events	1 / 14	not stated; safety; R0003844:Table 2
A3	events	2 / 17	not stated; safety; R0003844:Table 2
A4	events	0 / 18	not stated; safety; R0003844:Table 2

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	1 / 11	not stated; safety; R0003844:Table 2
A2	events	2 / 14	not stated; safety; R0003844:Table 2
A3	events	3 / 17	not stated; safety; R0003844:Table 2
A4	events	5 / 18	not stated; safety; R0003844:Table 2

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Results
A2	events	1 / 14	not stated; safety; R0003844:Results
A3	events	0 / 17	not stated; safety; R0003844:Results
A4	events	0 / 18	not stated; safety; R0003844:Results

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Table 2
A2	events	0 / 14	not stated; safety; R0003844:Table 2
A3	events	0 / 17	not stated; safety; R0003844:Table 2
A4	events	0 / 18	not stated; safety; R0003844:Table 2

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Table 2
A2	events	0 / 14	not stated; safety; R0003844:Table 2
A3	events	0 / 17	not stated; safety; R0003844:Table 2
A4	events	0 / 18	not stated; safety; R0003844:Table 2

Diabetic retinopathy complications (8 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; diabetic retinopathy; registry:adverse_events
A1	events	0 / 11	not stated; safety; vitreous haemorrhage; registry:adverse_events
A2	events	0 / 14	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	0 / 14	not stated; safety; vitreous haemorrhage; registry:adverse_events
A3	events	1 / 17	not stated; safety; diabetic retinopathy; registry:adverse_events
A3	events	1 / 17	not stated; safety; vitreous haemorrhage; registry:adverse_events
A4	events	0 / 18	not stated; safety; diabetic retinopathy; registry:adverse_events
A4	events	0 / 18	not stated; safety; vitreous haemorrhage; registry:adverse_events

Death by suicide (4 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 11	not stated; safety; R0003844:Table 2
A2	events	0 / 14	not stated; safety; R0003844:Table 2
A3	events	0 / 17	not stated; safety; R0003844:Table 2
A4	events	0 / 18	not stated; safety; R0003844:Table 2