Type 2 Diabetes
Conditions
Brief summary
The purpose of this study is to evaluate the glucodynamic effects of dulaglutide in Japanese participants with type 2 diabetes mellitus.
Interventions
DRUGDulaglutide
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
20 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Have type 2 diabetes (based on the World Health Organization \[WHO\] diagnostic criteria) for at least 1 year. * Have diet and exercise therapy only (no oral antihyperglycemic medication for at least 3 months prior to screening). * Have a fasting blood glucose value of ≥120 and ≤200 milligrams per deciliter (mg/dL) at screening. * Have a screening body weight of ≥50 and ≤80 kilograms.
Exclusion criteria
* Have known allergies to dulaglutide, or other glucagon-like peptide-1 (GLP-1) receptor agonists. * Have had a clinically significant cardiovascular disease. * Have a known clinically significant gastric emptying abnormality or have undergone gastric bypass surgery or restrictive bariatric surgery. * Have acute or chronic hepatitis, signs and symptoms of any other liver disease. * Have a history of chronic pancreatitis or acute idiopathic pancreatitis, or were diagnosed with any type of acute pancreatitis. * Have an estimated glomerular filtration rate (eGFR) \<30 milliliters/minute/1.73 meter squared. * In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glucose Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC[0-4h]) | Baseline, 4 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Postprandial Blood Glucose | Baseline, 4 Weeks | Change from baseline in postprandial blood glucose at 120 minutes at week 4. |
| Change From Baseline in Insulin Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | Baseline, 4 Weeks | 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. |
| Change From Baseline in C-Peptide Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | Baseline, 4 Weeks | 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. |
| Change From Baseline in Fasting Blood Glucose | Baseline, 4 Weeks | Change from baseline in fasting blood glucose obtained at pre-meal. |
| Change From Baseline in Triglyceride Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | Baseline, 4 Weeks | 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. |
| Number of Participants Who Develop Hypoglycemic Events | Baseline through 4 weeks | Number of participants who develop hypoglycemic events. |
| Change From Baseline in Glucagon Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | Baseline, 4 Weeks | 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall 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. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 7.1 |
| Duration of Diabetes | 8.5 years STANDARD_DEVIATION 7.7 |
| Fasting Blood Glucose | 164.67 milligram per deciliter (mg/dL) STANDARD_DEVIATION 22.18 |
| Race/Ethnicity, Customized Asian | 12 Participants |
| Region of Enrollment Japan | 12 Participants |
| Screening HbA1c | 7.9 percentage of HbA1c STANDARD_DEVIATION 1.2 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 5 / 12 | 4 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Change From Baseline in Glucose Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC[0-4h])
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.
Time frame: Baseline, 4 Weeks
Population: All participants who receive at least one dose of study drug and have evaluable pharmacodynamic data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dulaglutide | Change From Baseline in Glucose Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC[0-4h]) | -238.46 milligram*hour per deciliter (mg*h/dL) |
| Placebo | Change From Baseline in Glucose Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC[0-4h]) | 15.56 milligram*hour per deciliter (mg*h/dL) |
p-value: <0.000195% CI: [-337.76, -170.28]Mixed Models Analysis
Secondary
Change From Baseline in C-Peptide Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])
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.
Time frame: Baseline, 4 Weeks
Population: All participants who received at least one dose of study drug and had evaluable c-peptide data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dulaglutide | Change From Baseline in C-Peptide Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | 3.58 nanogram*h/milliliter (ng*h/mL) |
| Placebo | Change From Baseline in C-Peptide Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | -0.14 nanogram*h/milliliter (ng*h/mL) |
p-value: 0.026395% CI: [0.63, 6.81]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Blood Glucose
Change from baseline in fasting blood glucose obtained at pre-meal.
Time frame: Baseline, 4 Weeks
Population: All participants who received at least one dose of study drug and evaluable had fasting blood glucose data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Change From Baseline in Fasting Blood Glucose | -39.8 milligrams per deciliter (mg/dL) | Standard Deviation 33.3 |
| Placebo | Change From Baseline in Fasting Blood Glucose | -8.2 milligrams per deciliter (mg/dL) | Standard Deviation 21.5 |
Secondary
Change From Baseline in Glucagon Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])
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.
Time frame: Baseline, 4 Weeks
Population: All participants who received at least one dose of study drug and had evaluable glucagon data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dulaglutide | Change From Baseline in Glucagon Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | -16.39 picomole*h/Liter (pmol*h/L) |
| Placebo | Change From Baseline in Glucagon Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | -7.02 picomole*h/Liter (pmol*h/L) |
p-value: 0.0895% CI: [-20.16, 1.43]Mixed Models Analysis
Secondary
Change From Baseline in Insulin Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])
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.
Time frame: Baseline, 4 Weeks
Population: All participants who received at least one dose of study drug and had evaluable insulin data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dulaglutide | Change From Baseline in Insulin Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | 25.20 insulin units*h/mL (µU*h/mL) |
| Placebo | Change From Baseline in Insulin Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | -2.27 insulin units*h/mL (µU*h/mL) |
p-value: 0.0195% CI: [8.05, 46.87]Mixed Models Analysis
Secondary
Change From Baseline in Postprandial Blood Glucose
Change from baseline in postprandial blood glucose at 120 minutes at week 4.
Time frame: Baseline, 4 Weeks
Population: All participants who received at least one dose of study drug and had evaluable postprandial blood glucose data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dulaglutide | Change From Baseline in Postprandial Blood Glucose | -67.0 mg/dL | Standard Error 32.1 |
| Placebo | Change From Baseline in Postprandial Blood Glucose | 13.9 mg/dL | Standard Error 28.7 |
Secondary
Change From Baseline in Triglyceride Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])
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.
Time frame: Baseline, 4 Weeks
Population: All participants who received at least one dose of study drug and had evaluable triglyceride data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Dulaglutide | 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 |
| Placebo | Change From Baseline in Triglyceride Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h]) | 46.41 mg*h/dL |
p-value: 0.747595% CI: [-118.35, 87.57]Mixed Models Analysis
Secondary
Number of Participants Who Develop Hypoglycemic Events
Number of participants who develop hypoglycemic events.
Time frame: Baseline through 4 weeks
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dulaglutide | Number of Participants Who Develop Hypoglycemic Events | 0 Participants |
| Placebo | Number of Participants Who Develop Hypoglycemic Events | 0 Participants |