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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03315780
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 4
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the glucodynamic effects of dulaglutide in Japanese participants with type 2 diabetes mellitus.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Dulaglutide; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Phase 4 Study to Evaluate Glucodynamic Effects of Dulaglutide in Japanese Patients With Type 2 Diabetes Mellitus
• Actual Study Start Date: Oct 28, 2017
• Actual Primary Completion Date: Feb 28, 2018
• Actual Study Completion Date: Feb 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dulaglutide, Placebo Dulaglutide 0.75 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.	Drug: Dulaglutide; Administered SC; Other Names: LY2189265 ; Drug: Placebo; Administered SC
Experimental: Placebo, Dulaglutide Placebo administered SC once weekly for 4 weeks in Period 1 followed by Dulaglutide 0.75 mg administered SC for 4 weeks in Period 2. There is a 4 to 6 week washout period between Period 1 and Period 2.	Drug: Dulaglutide; Administered SC; Other Names: LY2189265 ; Drug: Placebo; Administered SC

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Change From Baseline in Fasting Blood Glucose [Baseline, 4 Weeks]

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

2. Change From Baseline in Postprandial Blood Glucose [Baseline, 4 Weeks]

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

3. 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.

4. 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.

5. 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.

6. 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.

7. Number of Participants Who Develop Hypoglycemic Events [Baseline through 4 weeks]

   Number of participants who develop hypoglycemic events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukuoka		Japan	812-0025

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Sep 26, 2017
• Statistical Analysis Plan - Oct 25, 2017

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03315780
• Other Study ID Numbers: 16730; H9X-JE-GBGK
• First Posted: Oct 20, 2017
• Last Update Posted: Sep 16, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Dulaglutide

Study Results

Participant Flow

Arm/Group Title	Dulaglutide Then Placebo	Placebo Then Dulaglutide
Arm/Group Description	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 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 Title: Period 1
STARTED	6	6
Received One Dose of Study Drug	6	6
COMPLETED	6	6
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	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.
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.9 (7.1)
Sex: Female, Male (Count of Participants)
Female	2 16.7%
Male	10 83.3%
Race/Ethnicity, Customized (Count of Participants)
Asian	12 100%
Region of Enrollment (Count of Participants)
Japan	12 100%
Duration of Diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.5 (7.7)
Screening HbA1c (percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of HbA1c]	7.9 (1.2)
Fasting Blood Glucose (milligram per deciliter (mg/dL)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [milligram per deciliter (mg/dL)]	164.67 (22.18)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Glucose Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC[0-4h])
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dulaglutide	Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo administered SC once weekly for four weeks.
Measure Participants	12	12
Least Squares Mean (95% Confidence Interval) [milligram*hour per deciliter (mg*h/dL)]	-238.46	15.56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dulaglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-254.02
	Confidence Interval	(2-Sided) 95%; -337.76 to -170.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose
Description	Change from baseline in fasting blood glucose obtained at pre-meal.
Time Frame	Baseline, 4 Weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dulaglutide	Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo administered SC once weekly for four weeks.
Measure Participants	12	12
Mean (Standard Deviation) [milligrams per deciliter (mg/dL)]	-39.8 (33.3)	-8.2 (21.5)

3. Secondary Outcome

Title	Change From Baseline in Postprandial Blood Glucose
Description	Change from baseline in postprandial blood glucose at 120 minutes at week 4.
Time Frame	Baseline, 4 Weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dulaglutide	Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo administered SC once weekly for four weeks.
Measure Participants	12	12
Mean (Standard Error) [mg/dL]	-67.0 (32.1)	13.9 (28.7)

4. Secondary Outcome

Title	Change From Baseline in Insulin Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dulaglutide	Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo administered SC once weekly for four weeks.
Measure Participants	12	12
Least Squares Mean (95% Confidence Interval) [insulin units*h/mL (µU*h/mL)]	25.20	-2.27

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dulaglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0100
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	27.46
	Confidence Interval	(2-Sided) 95%; 8.05 to 46.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in C-Peptide Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dulaglutide	Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo administered SC once weekly for four weeks.
Measure Participants	12	12
Least Squares Mean (95% Confidence Interval) [nanogram*h/milliliter (ng*h/mL)]	3.58	-0.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dulaglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0263
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.72
	Confidence Interval	(2-Sided) 95%; 0.63 to 6.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Glucagon Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dulaglutide	Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo administered SC once weekly for four weeks.
Measure Participants	12	12
Least Squares Mean (95% Confidence Interval) [picomole*h/Liter (pmol*h/L)]	-16.39	-7.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dulaglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0800
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.36
	Confidence Interval	(2-Sided) 95%; -20.16 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Triglyceride Area Under the Concentration Versus Time Curve From Time Zero to 4 Hours (AUC [0-4h])
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dulaglutide	Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo administered SC once weekly for four weeks.
Measure Participants	12	12
Least Squares Mean (95% Confidence Interval) [mg*h/dL]	31.02	46.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dulaglutide, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7475
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.39
	Confidence Interval	(2-Sided) 95%; -118.35 to 87.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants Who Develop Hypoglycemic Events
Description	Number of participants who develop hypoglycemic events.
Time Frame	Baseline through 4 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Dulaglutide	Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.	Placebo administered SC once weekly for four weeks.
Measure Participants	12	12
Count of Participants [Participants]	0 0%	0 NaN

Adverse Events

Time Frame	Baseline up to 14 weeks
Adverse Event Reporting Description	All participants who received at least one dose of study drug.
Arm/Group Title	Dulaglutide		Placebo
Arm/Group Description	Dulaglutide 0.75 mg administered SC once weekly for four weeks.		Placebo administered SC once weekly for four weeks.
All Cause Mortality
	Dulaglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Dulaglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Dulaglutide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)		4/12 (33.3%)
Gastrointestinal disorders
Diarrhoea	1/12 (8.3%)	1	1/12 (8.3%)	1
Nausea	1/12 (8.3%)	3	0/12 (0%)	0
Periodontal disease	0/12 (0%)	0	1/12 (8.3%)	1
Infections and infestations
Influenza	2/12 (16.7%)	2	0/12 (0%)	0
Pericoronitis	0/12 (0%)	0	1/12 (8.3%)	1
Periodontitis	0/12 (0%)	0	1/12 (8.3%)	1
Pharyngitis	1/12 (8.3%)	1	0/12 (0%)	0
Viral upper respiratory tract infection	0/12 (0%)	0	1/12 (8.3%)	1
Metabolism and nutrition disorders
Decreased appetite	1/12 (8.3%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.