Trial Outcomes & Findings for Study of How Dulaglutide Compares to Placebo in Participants With Type 2 Diabetes Who Are Also on Sulfonylurea Therapy (AWARD-8) (NCT NCT01769378)

NCT ID: NCT01769378

Last Updated: 2016-01-25

Results Overview

Least Squares Means (LS Means) of the HbA1c change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline HbA1c as covariate, via a Mixed-effects model for repeated measures (MMRM) analysis using restricted maximum likelihood (REML).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 300 participants
• Primary outcome timeframe: Baseline, 24 Weeks
• Results posted on: 2016-01-25

Participant Flow

Participant milestones

Measure	Dulaglutide Dulaglutide 1.5 milligram (mg) administered subcutaneously (SQ) once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Overall Study STARTED	240	60
Overall Study Received at Least 1 Dose of Study Drug	239	60
Overall Study COMPLETED	215	56
Overall Study NOT COMPLETED	25	4

Reasons for withdrawal

Measure	Dulaglutide Dulaglutide 1.5 milligram (mg) administered subcutaneously (SQ) once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Overall Study Adverse Event	10	0
Overall Study Entry criteria not met	1	0
Overall Study Protocol Violation	1	1
Overall Study Withdrawal by Subject	10	3
Overall Study Sponsor Decision	1	0
Overall Study Lost to Follow-up	2	0

Baseline Characteristics

Study of How Dulaglutide Compares to Placebo in Participants With Type 2 Diabetes Who Are Also on Sulfonylurea Therapy (AWARD-8)

Baseline characteristics by cohort

Measure	Dulaglutide n=239 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Total n=299 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	182 Participants n=5 Participants	49 Participants n=7 Participants	231 Participants n=5 Participants
Age, Categorical >=65 years	57 Participants n=5 Participants	11 Participants n=7 Participants	68 Participants n=5 Participants
Age, Continuous	57.73 years STANDARD_DEVIATION 10.20 • n=5 Participants	58.23 years STANDARD_DEVIATION 7.40 • n=7 Participants	57.83 years STANDARD_DEVIATION 9.70 • n=5 Participants
Sex: Female, Male Female	135 Participants n=5 Participants	32 Participants n=7 Participants	167 Participants n=5 Participants
Sex: Female, Male Male	104 Participants n=5 Participants	28 Participants n=7 Participants	132 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	112 Participants n=5 Participants	27 Participants n=7 Participants	139 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	127 Participants n=5 Participants	33 Participants n=7 Participants	160 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	21 Participants n=5 Participants	5 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) White	202 Participants n=5 Participants	47 Participants n=7 Participants	249 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Argentina	29 participants n=5 Participants	8 participants n=7 Participants	37 participants n=5 Participants
Region of Enrollment Austria	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Region of Enrollment Romania	78 participants n=5 Participants	18 participants n=7 Participants	96 participants n=5 Participants
Region of Enrollment United States	57 participants n=5 Participants	14 participants n=7 Participants	71 participants n=5 Participants
Region of Enrollment South Africa	7 participants n=5 Participants	3 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Mexico	40 participants n=5 Participants	10 participants n=7 Participants	50 participants n=5 Participants
Region of Enrollment Slovenia	13 participants n=5 Participants	3 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Croatia	9 participants n=5 Participants	2 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Puerto Rico	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 24 Weeks

Population: Participants who were randomized and received at least one dose of study drug with evaluable HbA1c data at both baseline and post-baseline.

Least Squares Means (LS Means) of the HbA1c change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline HbA1c as covariate, via a Mixed-effects model for repeated measures (MMRM) analysis using restricted maximum likelihood (REML).

Outcome measures

Measure	Dulaglutide n=215 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=53 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Change From Baseline in Glycosylated Hemoglobin A1c (HbA1c) at 24 Weeks	-1.38 percent change of HbA1c Standard Error 0.08	-0.11 percent change of HbA1c Standard Error 0.14

SECONDARY outcome

Timeframe: 24 Weeks

Population: Participants who were randomized and received at least one dose of study drug with evaluable HbA1c data.

The percentage of participants who achieved the target HbA1c values at endpoint will be analyzed with a repeated logistic regression model (the generalized estimation equation [GEE] model). The model includes country, treatment, visit and treatment interaction and baseline HbA1c as a continuous covariate.

Outcome measures

Measure	Dulaglutide n=215 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=53 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks Percent Achieved <7.0 HbA1c Level	55.3 percentage of participants	18.9 percentage of participants
Percentage of Participants Who Achieve HbA1c <7.0% and ≤6.5% at 24 Weeks Percent Achieved ≤6.5 HbA1c Level	40.0 percentage of participants	9.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 24 Weeks

Population: Participants who received at least one dose of study drug and had evaluable FSG data at both baseline and post-baseline. LOCF was used to impute missing post-baseline values. If no data after date of randomization, the endpoint was considered missing.

LS Means of the FSG from baseline to primary endpoint was adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline FSG as covariate, via Analysis of Covariance Model (ANCOVA) with Last Observation Carried Forward (LOCF).

Outcome measures

Measure	Dulaglutide n=218 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=51 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Change From Baseline in Fasting Serum Glucose (FSG) at 24 Weeks	-30.60 milligrams per deciliter (mg/dL) Standard Error 4.46	2.93 milligrams per deciliter (mg/dL) Standard Error 6.76

SECONDARY outcome

Timeframe: Baseline, 24 Weeks

Population: Participants who received at least one dose of study drug and had evaluable body weight data at both baseline and post-baseline.

LS Means of the body weight change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline body weight as covariate, via a MMRM analysis using REML.

Outcome measures

Measure	Dulaglutide n=212 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=53 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Change From Baseline in Body Weight at 24 Weeks	-0.91 kilograms (kg) Standard Error 0.21	-0.24 kilograms (kg) Standard Error 0.40

SECONDARY outcome

Timeframe: Baseline, 24 Weeks

Population: Participants who received at least one dose of study drug and evaluable BMI data at both baseline and post-baseline.

LS Means of the BMI change from baseline to primary endpoint was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline BMI as covariate, via a MMRM analysis using REML.

Outcome measures

Measure	Dulaglutide n=212 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=53 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Change From Baseline in Body Mass Index (BMI) at 24 Weeks	-0.32 kilograms per/square meter kg/m^2 Standard Error 0.08	-0.10 kilograms per/square meter kg/m^2 Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline, 24 Weeks

Population: Participants who received at least one dose of study drug and had evaluable SMPG data at both baseline and post-baseline.

LS Means of the SMPG change from baseline to primary endpoint at week 24 was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect and baseline SMPG value as covariate, via a MMRM analysis using REML.

Outcome measures

Measure	Dulaglutide n=203 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=49 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Change From Baseline in Mean of All 7-Point Self Monitored Plasma Glucose (SMPG) at 24 Weeks	-37.22 mg/dL Standard Error 3.10	-8.27 mg/dL Standard Error 4.77

SECONDARY outcome

Timeframe: Baseline through 24 Weeks, 30-day Follow Up

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

Information on cardiovascular (CV) risk factors was collected at baseline. Deaths and nonfatal cardiovascular adverse events (AEs) were adjudicated by an external committee of physicians with cardiology expertise. Nonfatal cardiovascular AEs to be adjudicated included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions, and cerebrovascular events, including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with CV events confirmed by adjudication is summarized cumulatively at 24 weeks plus 30-day follow up. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.

Outcome measures

Measure	Dulaglutide n=239 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Number of Participants With Reported and Adjudicated Cardiovascular Events Any reported CV events	2 participants	0 participants
Number of Participants With Reported and Adjudicated Cardiovascular Events Any adjudicated nonfatal CV events	2 participants	0 participants
Number of Participants With Reported and Adjudicated Cardiovascular Events Any confirmed adjudicated CV deaths	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline through 24 Weeks, 30-day Follow Up

Population: ITT population: all randomized participants who received at least one dose of study drug.

The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 24 weeks plus 30-day follow up. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Outcome measures

Measure	Dulaglutide n=239 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Number of Participants With Adjudicated Acute Pancreatitis Events	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, 24 Weeks

Population: Participants who received at least one dose of study drug and evaluable calcitonin data at baseline and post-baseline.

Outcome measures

Measure	Dulaglutide n=215 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=59 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Change From Baseline in Calcitonin at 24 Weeks	0.00 picogram per milliliter (pg/ml) Interval 0.0 to 0.0	0.00 picogram per milliliter (pg/ml) Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: Baseline through 24 Weeks

Population: ITT Population: all randomized participants who received at least one dose of study drug.

Hypoglycemic events (HE) were classified as severe (defined as episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (defined as any time a participant feels that he/she is experiencing symptoms and/or signs associated with hypoglycemia, and has a plasma glucose level of =<3.9 mmol/L), asymptomatic (defined as events not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose of =<3.9 mmol/L), nocturnal (defined as any hypoglycemic event that occurred between bedtime and waking), or probable symptomatic (defined as events during which symptoms of hypoglycemia were not accompanied by a plasma glucose determination). Percentage is calculated as the number of participants reporting HE each visit/ the total number of participants reporting HE during the entire study treatment period.

Outcome measures

Measure	Dulaglutide n=239 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Percentage of Participants With Self-Reported Events of Hypoglycemia Symptomatic	11.3 percentage of participants	1.7 percentage of participants
Percentage of Participants With Self-Reported Events of Hypoglycemia Asymptomatic	13.4 percentage of participants	1.7 percentage of participants
Percentage of Participants With Self-Reported Events of Hypoglycemia Probable	2.5 percentage of participants	0.0 percentage of participants
Percentage of Participants With Self-Reported Events of Hypoglycemia Severe	0 percentage of participants	0 percentage of participants
Percentage of Participants With Self-Reported Events of Hypoglycemia Nocturnal	6.7 percentage of participants	1.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 24 weeks

Population: ITT population: all randomized participants who received at least one dose of study drug.

The hypoglycemia rate per 30 days during defined period is calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period*30 days.

Outcome measures

Measure	Dulaglutide n=239 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Rate of HE Adjusted Per 30 Days Severe HE	0 number of events/participants/30 days Standard Deviation 0.0	0 number of events/participants/30 days Standard Deviation 0.0
Rate of HE Adjusted Per 30 Days Total HE	0.19 number of events/participants/30 days Standard Deviation 0.59	0.01 number of events/participants/30 days Standard Deviation 0.03
Rate of HE Adjusted Per 30 Days Documented symptomatic HE	0.07 number of events/participants/30 days Standard Deviation 0.33	0.00 number of events/participants/30 days Standard Deviation 0.02
Rate of HE Adjusted Per 30 Days Asymptomatic HE	0.11 number of events/participants/30 days Standard Deviation 0.45	0.00 number of events/participants/30 days Standard Deviation 0.02
Rate of HE Adjusted Per 30 Days Nocturnal HE	0.02 number of events/participants/30 days Standard Deviation 0.16	0.00 number of events/participants/30 days Standard Deviation 0.02
Rate of HE Adjusted Per 30 Days Probable symptomatic HE	0.01 number of events/participants/30 days Standard Deviation 0.04	0 number of events/participants/30 days Standard Deviation 0.0

SECONDARY outcome

Timeframe: Baseline through 24 Weeks

Population: ITT population: all randomized participants who received at least one dose of study drug.

Additional Intervention: any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation.

Outcome measures

Measure	Dulaglutide n=239 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Percentage of Participants Requiring Additional Intervention for Severe, Persistent Hyperglycemia	2.1 percentage of participants	11.7 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 24 Weeks

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

An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period.

Outcome measures

Measure	Dulaglutide n=239 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Time to Initiation of Additional Intervention for Severe, Persistent Hyperglycemia	22.59 weeks Standard Error 0.36	22.47 weeks Standard Error 0.66

SECONDARY outcome

Timeframe: Baseline up to 4 Weeks Post-Last Dose of Study Drug

Population: ITT population: all randomized participants who received at least one dose of study drug.

Number of participants with treatment emergent (TE) dulaglutide anti-drug antibodies from postbaseline to follow up were summarized. A participant is considered to have TE dulaglutide ADA if the participant has at least one titer that is treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.

Outcome measures

Measure	Dulaglutide n=239 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Dulaglutide Anti-Drug Antibodies (ADA)	2 participants	—

SECONDARY outcome

Timeframe: Baseline, 24 Weeks

Population: All participants who received at least one dose of study drug and had evaluable lipase data at both baseline and post-baseline. LOCF was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.

A summary of changes in lipase evaluation from baseline to endpoint.

Outcome measures

Measure	Dulaglutide n=233 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Change From Baseline in Lipase	8.0 Units/Liter Interval 1.0 to 18.0	4.5 Units/Liter Interval -2.5 to 15.5

SECONDARY outcome

Timeframe: Baseline, 24 Weeks

Population: Participants who received at least one dose of study drug and had evaluable amylase data at both baseline and post-baseline. LOCF was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.

A summary of changes in amylase evaluation from baseline to endpoint.

Outcome measures

Measure	Dulaglutide n=233 Participants Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 Participants Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Change From Baseline in Amylase	8.0 Units/Liter Interval 1.0 to 18.0	2.0 Units/Liter Interval -5.0 to 11.0

Adverse Events

Dulaglutide

Serious events: 9 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dulaglutide n=239 participants at risk Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 participants at risk Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Nervous system disorders Cerebrovascular accident	0.42% 1/239 • Number of events 1	0.00% 0/60
Cardiac disorders Angina pectoris	0.42% 1/239 • Number of events 1	0.00% 0/60
Infections and infestations Osteomyelitis	0.42% 1/239 • Number of events 1	0.00% 0/60
Infections and infestations Otitis media	0.42% 1/239 • Number of events 1	0.00% 0/60
Infections and infestations Pulmonary tuberculosis	0.42% 1/239 • Number of events 1	0.00% 0/60
Injury, poisoning and procedural complications Ulna fracture	0.42% 1/239 • Number of events 1	0.00% 0/60
Metabolism and nutrition disorders Hypoglycemia	0.42% 1/239 • Number of events 1	0.00% 0/60
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.42% 1/239 • Number of events 1	0.00% 0/60
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anaplastic astrocytoma	0.42% 1/239 • Number of events 1	0.00% 0/60

Other adverse events

Measure	Dulaglutide n=239 participants at risk Dulaglutide 1.5 mg administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.	Placebo n=60 participants at risk Placebo administered SQ once weekly for 24 weeks added to the participant's prescribed glimepiride dose.
Gastrointestinal disorders Diarrhoea	8.4% 20/239 • Number of events 30	0.00% 0/60
Gastrointestinal disorders Eructation	5.9% 14/239 • Number of events 24	0.00% 0/60
Gastrointestinal disorders Nausea	10.5% 25/239 • Number of events 31	0.00% 0/60
Metabolism and nutrition disorders Hyperglycemia	0.42% 1/239 • Number of events 1	5.0% 3/60 • Number of events 3

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60