Trial Outcomes & Findings for A Study of the Glucodynamic Effects of Dulaglutide (LY2189265) in Japanese Participants With Type 2 Diabetes (NCT NCT03315780)

Results Overview

Least square (LS) means of glucose AUC 0-4h change from baseline was calculated using mixed-effects linear model. The model will include treatment, sequence, period, week, and treatment-by-week as fixed effects, baseline as a covariate, and participant as random effect.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

12 participants

Primary outcome timeframe

Baseline, 4 Weeks

Results posted on

2019-09-16

Participant Flow

Participant milestones

Participant milestones
Measure	Dulaglutide Then Placebo Dulaglutide 0.75 milligrams (mg) administered subcutaneously (SC) once weekly for 4 weeks in Period 1 followed by placebo administered SC once weekly for 4 weeks in period 2. There is a 4 to 6 week washout period between Period 1 and Period 2.	Placebo Then Dulaglutide Placebo administered SC once weekly for 4 weeks in Period 1 followed byDulaglutide 0.75 mg administered SC once weekly for 4 weeks in Period 2. There is a 4 to 6 week washout period between Period 1 and Period 2.
Period 1 STARTED	6	6
Period 1 Received One Dose of Study Drug	6	6
Period 1 COMPLETED	6	6
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	6	6
Period 2 COMPLETED	6	6
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of the Glucodynamic Effects of Dulaglutide (LY2189265) in Japanese Participants With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Overall n=12 Participants Participants were randomized to one of two treatment sequences: Dulaglutide 0.75 mg administered subcutaneously (SC) in Period 1 and placebo administered SC in Period 2 or placebo administered SC in Period 1 and Dulaglutide 0.75 mg administered in Period 2.
Age, Continuous	58.9 years STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants
Race/Ethnicity, Customized Asian	12 Participants n=5 Participants
Region of Enrollment Japan	12 Participants n=5 Participants
Duration of Diabetes	8.5 years STANDARD_DEVIATION 7.7 • n=5 Participants
Screening HbA1c	7.9 percentage of HbA1c STANDARD_DEVIATION 1.2 • n=5 Participants
Fasting Blood Glucose	164.67 milligram per deciliter (mg/dL) STANDARD_DEVIATION 22.18 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 4 Weeks

Population: All participants who receive at least one dose of study drug and have evaluable pharmacodynamic data.

Least square (LS) means of glucose AUC 0-4h change from baseline was calculated using mixed-effects linear model. The model will include treatment, sequence, period, week, and treatment-by-week as fixed effects, baseline as a covariate, and participant as random effect.

Outcome measures

Outcome measures
Measure	Dulaglutide n=12 Participants Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 Participants Placebo administered SC once weekly for four weeks.
Change From Baseline in Glucose Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC[0-4h])	-238.46 milligramhour per deciliter (mgh/dL) Interval -293.87 to -183.05	15.56 milligramhour per deciliter (mgh/dL) Interval -71.27 to 102.39

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

Population: All participants who received at least one dose of study drug and evaluable had fasting blood glucose data.

Change from baseline in fasting blood glucose obtained at pre-meal.

Outcome measures

Outcome measures
Measure	Dulaglutide n=12 Participants Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 Participants Placebo administered SC once weekly for four weeks.
Change From Baseline in Fasting Blood Glucose	-39.8 milligrams per deciliter (mg/dL) Standard Deviation 33.3	-8.2 milligrams per deciliter (mg/dL) Standard Deviation 21.5

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

Population: All participants who received at least one dose of study drug and had evaluable postprandial blood glucose data.

Change from baseline in postprandial blood glucose at 120 minutes at week 4.

Outcome measures

Outcome measures
Measure	Dulaglutide n=12 Participants Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 Participants Placebo administered SC once weekly for four weeks.
Change From Baseline in Postprandial Blood Glucose	-67.0 mg/dL Standard Error 32.1	13.9 mg/dL Standard Error 28.7

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

Population: All participants who received at least one dose of study drug and had evaluable insulin data.

LS mean of the insulin change from baseline was analyzed using a mixed-effects linear model. The model includes treatment, sequence, period, week and treat-by-sequence as fixed effects, baseline as a covariate and participant as random effect.

Outcome measures

Outcome measures
Measure	Dulaglutide n=12 Participants Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 Participants Placebo administered SC once weekly for four weeks.
Change From Baseline in Insulin Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])	25.20 insulin unitsh/mL (µUh/mL) Interval 7.29 to 43.1	-2.27 insulin unitsh/mL (µUh/mL) Interval -11.39 to 6.85

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

Population: All participants who received at least one dose of study drug and had evaluable c-peptide data.

LS mean of C-peptide change from baseline was analyzed using a mixed-effects linear model. The model includes treatment, sequence, period, week and treat-by-sequence as fixed effects, baseline as a covariate and participant as random effect.

Outcome measures

Outcome measures
Measure	Dulaglutide n=12 Participants Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 Participants Placebo administered SC once weekly for four weeks.
Change From Baseline in C-Peptide Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])	3.58 nanogramh/milliliter (ngh/mL) Interval 0.44 to 6.72	-0.14 nanogramh/milliliter (ngh/mL) Interval -1.24 to 0.96

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

Population: All participants who received at least one dose of study drug and had evaluable glucagon data.

LS mean of glucagon change from baseline was analyzed using a mixed-effects linear model. The model includes treatment, sequence, period, week and treat-by-sequence as fixed effects, baseline as a covariate and participant as random effect.

Outcome measures

Outcome measures
Measure	Dulaglutide n=12 Participants Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 Participants Placebo administered SC once weekly for four weeks.
Change From Baseline in Glucagon Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])	-16.39 picomoleh/Liter (pmolh/L) Interval -25.69 to -7.09	-7.02 picomoleh/Liter (pmolh/L) Interval -12.81 to -1.24

SECONDARY outcome

Timeframe: Baseline, 4 Weeks

Population: All participants who received at least one dose of study drug and had evaluable triglyceride data.

LS mean of triglyceride change from baseline was analyzed using a mixed-effects linear model. The model includes treatment, sequence, period, week and treat-by-sequence as fixed effects, baseline as a covariate and participant as random effect.

Outcome measures

Outcome measures
Measure	Dulaglutide n=12 Participants Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 Participants Placebo administered SC once weekly for four weeks.
Change From Baseline in Triglyceride Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])	31.02 mg*h/dL Interval -54.7 to 116.74	46.41 mg*h/dL Interval -76.55 to 169.38

SECONDARY outcome

Timeframe: Baseline through 4 weeks

Population: All participants who received at least one dose of study drug.

Number of participants who develop hypoglycemic events.

Outcome measures

Outcome measures
Measure	Dulaglutide n=12 Participants Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 Participants Placebo administered SC once weekly for four weeks.
Number of Participants Who Develop Hypoglycemic Events	0 Participants	0 Participants

Adverse Events

Dulaglutide

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Dulaglutide n=12 participants at risk Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo n=12 participants at risk Placebo administered SC once weekly for four weeks.
Gastrointestinal disorders Diarrhoea	8.3% 1/12 • Number of events 1 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	8.3% 1/12 • Number of events 1 • Baseline up to 14 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	8.3% 1/12 • Number of events 3 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	0.00% 0/12 • Baseline up to 14 weeks All participants who received at least one dose of study drug.
Gastrointestinal disorders Periodontal disease	0.00% 0/12 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	8.3% 1/12 • Number of events 1 • Baseline up to 14 weeks All participants who received at least one dose of study drug.
Infections and infestations Influenza	16.7% 2/12 • Number of events 2 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	0.00% 0/12 • Baseline up to 14 weeks All participants who received at least one dose of study drug.
Infections and infestations Pericoronitis	0.00% 0/12 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	8.3% 1/12 • Number of events 1 • Baseline up to 14 weeks All participants who received at least one dose of study drug.
Infections and infestations Periodontitis	0.00% 0/12 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	8.3% 1/12 • Number of events 1 • Baseline up to 14 weeks All participants who received at least one dose of study drug.
Infections and infestations Pharyngitis	8.3% 1/12 • Number of events 1 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	0.00% 0/12 • Baseline up to 14 weeks All participants who received at least one dose of study drug.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/12 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	8.3% 1/12 • Number of events 1 • Baseline up to 14 weeks All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	8.3% 1/12 • Number of events 1 • Baseline up to 14 weeks All participants who received at least one dose of study drug.	0.00% 0/12 • Baseline up to 14 weeks All participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60