A Study of Investigational Dulaglutide Doses in Participa... | NCT02973100

ID	Type	Description	Link
H9X-MC-GBGJ	Other Identifier	Eli Lilly and Company
2016-002494-34	EudraCT Number

Label	Type	Description	Intervention Names
Dulaglutide 4.5mg	Experimental	4.5mg of Dulaglutide administered subcutaneously (SC)	Drug: Dulaglutide
Dulaglutide 3.0mg	Experimental	3.0mg of Dulaglutide administered SC	Drug: Dulaglutide
Dulaglutide 1.5mg	Active Comparator	1.5mg of Dulaglutide administered SC	Drug: Dulaglutide
Placebo	Placebo Comparator	Placebo administered SC	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Dulaglutide	Drug	Administered SC	Dulaglutide 1.5mg Dulaglutide 3.0mg Dulaglutide 4.5mg

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline as a covariate, pooled country, treatment, time, treatment*time as fixed effects.	Baseline, Week 18

Measure	Description	Time Frame
Percentage of Participants With HbA1c of <7.0%	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.	Week 18
Change From Baseline in Fasting Serum Glucose (FSG)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have had type 2 diabetes (T2D) for ≥6 months according to the World Health Organization (WHO) classification
Have HbA1c of 7.0% to 10.0%, inclusive, as assessed by the central laboratory
Have been treated with stable doses of metformin for at least 3 months
Have a body mass index (BMI) ≥25 kilograms per square meter

Exclusion Criteria:

Have type 1 diabetes (T1D)
Have used any glucose-lowering medication other than metformin 3 months prior to study entry or during screening/lead-in period or have used any glucagon-like peptide-1 receptor agonists (GLP-1 RAs) at any time in the past
Have had any of the following cardiovascular conditions: acute myocardial infarction (MI), New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident (stroke)
Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial
Have had chronic or acute pancreatitis any time prior to study entry
Have an estimated glomerular filtration rate (eGFR) <45 milliliters/minute/1.73 square meter, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation
Have serum calcitonin ≥20 picograms per milliliter, as determined by the central laboratory at study entry

Name	Affiliation	Role
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 Director

Facility	Status	City	State	ZIP	Country	Contacts
Parexel Early Phase Unit at Glendale		Glendale	California	91206-4140	United States
Marin Endocrine Associates

Label	URL
A Study of Investigational Dulaglutide Doses in Participants With Type 2 Diabetes on Metformin Monotherapy	View source

ID	Title	Description
FG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.
FG001	Dulaglutide 1.5 Milligrams (mg)	Participants received 1.5mg of dulaglutide QW by SC injection.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
SAP	No	Yes	No	Statistical Analysis Plan	Dec 8, 2016	May 8, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Hemoglobin A1c (HbA1c)

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline as a covariate, pooled country, treatment, time, treatment*time as fixed effects.

All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue data for Hemoglobin A1c.

Posted

Least Squares Mean

Standard Error

Percentage of glycosylated hemoglobin

Baseline, Week 18

ID	Title	Description
OG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.
OG001	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
OG002	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.
OG003	Dulaglutide 4.5mg	Participants received 4.5mg of dulaglutide QW by SC injection.

Units	Counts
Participants	OG00070 OG00173 OG00273 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.44± 0.101 OG001-1.23± 0.099 OG002-1.31± 0.099 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		<.001		Mean Difference (Final Values)	-0.80			2-Sided	95	-1.07	-0.53					Superiority
OG000 OG002		Mixed Models Analysis		<0.001

Secondary

Percentage of Participants With HbA1c of <7.0%

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue data for Hemoglobin A1c.

Posted

Number

Percentage of Participants

Week 18

ID	Title	Description
OG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.
OG001	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
OG002	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.
OG003	Dulaglutide 4.5mg	Participants received 4.5mg of dulaglutide QW by SC injection.

Secondary

Change From Baseline in Fasting Serum Glucose (FSG)

Fasting serum glucose (FSG) is a test to determine how much glucose (sugar) is in a serum sample after an overnight fast. Least Squares (LS) means was determined by MMRM methodology with baseline as a covariate, pooled country, baseline HbA1c strata using >=8% as cutoff, treatment, time, treatment*time as fixed effects.

All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue data for FSG.

Posted

Least Squares Mean

Standard Error

millimole/liter (mmol/L)

Baseline, Week 18

ID	Title	Description
OG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.
OG001	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
OG002	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.
OG003	Dulaglutide 4.5mg	Participants received 4.5mg of dulaglutide QW by SC injection.

Secondary

Change From Baseline in Body Weight

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline as a covariate, pooled country, baseline HbA1c strata using >=8% as cutoff, treatment, time, treatment*time as fixed effects.

All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue data for body weight.

Posted

Least Squares Mean

Standard Error

Kilograms (Kg)

Baseline, Week 18

ID	Title	Description
OG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.
OG001	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
OG002	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.
OG003	Dulaglutide 4.5mg	Participants received 4.5mg of dulaglutide QW by SC injection.

Secondary

Percentage of Participants Discontinuing Study Drug Due to Adverse Events

Adverse event (AE) defined as any unfavorable medical event, newly emerged or a deterioration of a preexisting condition, in other words any untoward medical occurrence in a patient administered a pharmaceutical product, without regard to the possibility of a causal relationship, that occurred after the visit for informed consent and up to the visit for completion of administration, or discontinuation.

All randomized participants who received study drug and had postbaseline data for safety analyses.

Posted

Number

Percentage of Participants

Baseline through Week 18

ID	Title	Description
OG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.
OG001	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
OG002	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.
OG003	Dulaglutide 4.5mg

Secondary

Rate of Documented Symptomatic Hypoglycemia

Hypoglycemic events (HE) were classified as severe, documented symptomatic (defined as an HE with typical symptoms of hypoglycemia and a blood glucose level of ≤3.9 millimoles per liter [mmol/L]). Hypoglycemia rate per 30 days was summarized at each visit by treatment group. The rate of hypoglycemia was analyzed using a generalized estimation equations model with a negative binomial distribution and a Log link. LS mean was determined by MMRM methodology with baseline hypoglycemia rate, pooled country, HbA1c at Baseline, treatment, with log of exposure in days divided by 365.25 as the offset.

All randomized participants who received at least one dose of study drug and had postbaseline values, excluding post rescue values for hypoglycemic episodes.

Posted

Least Squares Mean

Standard Error

Episodes/participant/365.25 days

Week 18

ID	Title	Description
OG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.
OG001	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
OG002	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.

Secondary

Pharmacokinetics (PK): The Maximum Drug Concentration at Steady State (Cmax,ss) of Dulaglutide

Plasma samples for PK analysis were combined measure obtained from 0, 2, 4, 6, 10, 18, 22 weeks and until early termination of the visit. Cmax takes all time points post dose into account and one value was reported.

All randomized participants who received at least one dose of the study drug and have evaluable PK data.

Posted

Mean

90% Confidence Interval

nanogram per milliliter (ng/mL)

0, 2, 4, 6, 10, 18, 22 weeks and early termination

ID	Title	Description
OG000	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
OG001	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.
OG002	Dulaglutide 4.5mg	Participants received 4.5mg of dulaglutide QW by SC injection.

Units	Counts
Participants

Secondary

Pharmacokinetics: Area Under the Concentration-Time Curve at Steady State From Time Zero to 168 Hours (AUC[0-168], ss) of Dulaglutide

AUC[0-168h] is a combined measure obtained from 0, 2, 4, 6, 10, 18, 22 weeks and until early termination of the visit.

All randomized participants who received at least one dose of the study drug and have evaluable PK data.

Posted

Mean

90% Confidence Interval

nanogram*hour per milliliter (ng*h/mL)

0, 2, 4, 6, 10, 18, 22 weeks and early termination

ID	Title	Description
OG000	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
OG001	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.
OG002	Dulaglutide 4.5mg	Participants received 4.5mg of dulaglutide QW by SC injection.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG0030 events0 affected76 at risk
Atrioventricular block second degree	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected81 at risk EG0020 events0 affected79 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected81 at risk EG0020 events0 affected79 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected81 at risk EG0020 events0 affected79 at risk EG003
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG003
Cholecystitis infective	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Fungal oesophagitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Peritonsillar abscess	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Traumatic intracranial haemorrhage	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG003
Hyperglycaemic hyperosmolar nonketotic syndrome	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected81 at risk EG0020 events0 affected79 at risk EG003
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003
Hypotension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0021 events1 affected79 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0010 events0 affected81 at risk EG0022 events2 affected79 at risk EG00310 events4 affected76 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0014 events3 affected81 at risk EG0021 events1 affected79 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0015 events5 affected81 at risk EG0024 events4 affected79 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00010 events9 affected81 at risk EG00117 events9 affected81 at risk EG00234 events18 affected79 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG00110 events6 affected81 at risk EG0025 events5 affected79 at risk EG003
Eructation	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0013 events3 affected81 at risk EG0021 events1 affected79 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0015 events5 affected81 at risk EG0021 events1 affected79 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0005 events4 affected81 at risk EG00145 events18 affected81 at risk EG00232 events20 affected79 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0006 events4 affected81 at risk EG00120 events9 affected81 at risk EG00215 events9 affected79 at risk EG003
Fatigue	General disorders	MedDRA 20.0	Systematic Assessment	EG0003 events2 affected81 at risk EG0011 events1 affected81 at risk EG0024 events4 affected79 at risk EG003
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0011 events1 affected81 at risk EG0024 events4 affected79 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0005 events3 affected81 at risk EG0011 events1 affected81 at risk EG0025 events5 affected79 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0007 events5 affected81 at risk EG0012 events2 affected81 at risk EG0026 events6 affected79 at risk EG003
Weight decreased	Investigations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected81 at risk EG0016 events3 affected81 at risk EG0026 events5 affected79 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0013 events3 affected81 at risk EG00217 events13 affected79 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0010 events0 affected81 at risk EG0022 events1 affected79 at risk EG003
Dizziness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0006 events4 affected81 at risk EG0016 events4 affected81 at risk EG0026 events5 affected79 at risk EG003
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG00011 events7 affected81 at risk EG0014 events4 affected81 at risk EG00213 events10 affected79 at risk EG003
Hypertension	Vascular disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected81 at risk EG0011 events1 affected81 at risk EG0024 events4 affected79 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Title	Description
BG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.
BG001	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.
BG002	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.
BG003	Dulaglutide 4.5mg	Participants received 4.5mg of dulaglutide QW by SC injection.
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo once weekly (QW) by subcutaneous (SC) injection.	81	4	81	29	81
EG001	Dulaglutide 1.5mg	Participants received 1.5mg of dulaglutide QW by SC injection.	81	3	81	36	81
EG002	Dulaglutide 3.0mg	Participants received 3.0mg of dulaglutide QW by SC injection.	79	7	79	49	79
EG003	Dulaglutide 4.5mg	Participants received 4.5mg of dulaglutide QW by SC injection.	76	3	76	39	76