Type 2 Diabetes
Conditions
Keywords
Pediatrics
Brief summary
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of the study drug dulaglutide compared to placebo in pediatric participants with type 2 diabetes. The study duration is approximately 60 weeks.
Interventions
DRUGDulaglutide
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Have type 2 diabetes, treated with diet and exercise, with or without metformin and/or basal insulin. Metformin and/or basal insulin dose must be stable for at least 8 weeks prior to study screening. * Have HbA1c \>6.5% to ≤11% at screening visit. If newly diagnosed and not on medicine for diabetes, HbA1c must be between \>6.5 % to ≤9%. * Have a BMI (body mass index) \>85 percentile for age, gender and body weight ≥50 kilograms (110 pounds).
Exclusion criteria
* Known type 1 diabetes, or positive GAD65 or IA2 antibodies, or history of diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. * A history of, or at risk for pancreatitis. * Self or family history of Multiple Endocrine Neoplasia (MEN) type 2A or B, thyroid C-cell hyperplasia or medullary thyroid cancer, or a blood calcitonin result ≥20 picograms per milliliter (pg/ml) at screening. * A systolic blood pressure of ≥160 millimeters of mercury (mmHg) or diastolic ≥100 mmHg. * Active or treated cancer. * A blood disorder where an accurate HbA1c may not be obtainable. * A female of childbearing age, sexually active and not on birth control. * Pregnant or plan to be pregnant during the study, or breastfeeding. * Taking any diabetic medication other than metformin or basal insulin and have not stopped it 3 months prior to the screening visit (6 weeks for bolus or mealtime insulin). * Have taken oral steroids within the last 60 days or more than 20 days use within the past year or 1000 micrograms fluticasone propionate per day. * Using prescription weight loss medications in the last 30 days, or plan to use. * Taking psychiatric medications for depression or illness or attention deficit hyperactivity disorder (ADHD) if, the doses has changed within the last 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses) at Week 26 | Baseline, Week 26 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean in HbA1c was calculated using a restricted maximum likelihood (REML) based mixed-effects model for repeated measures (MMRM) and adjusted by, baseline + insulin Use + metformin Use + treatment + time + treatment\*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | Baseline, Week 26 | Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis and adjusted by baseline, strata, treatment, time, treatment\*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group \[ less than (\<) 8%, greater than or equal to (\>=) 8%). |
| Percentage of Participants With HbA1c ≤7.0% | Week 26 | The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. |
| Change From Baseline in Body Mass Index (BMI) at Week 26 | Baseline, Week 26 | BMI is an estimate of body fat based on body weight divided by height squared. LS mean were calculated using a MMRM analysis and adjusted by baseline, strata, treatment, time, treatment\*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group (\< 8%, \>= 8%). |
| Percentage of Participants With Self-Reported Events of Hypoglycemia | Week 26 | Summary and analysis of Incidence of all hypoglycemia with Plasma Glucose \<54mg/dL. |
| Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia | Week 26 | Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia was summarized. |
| Number of Participants With Adjudicated Pancreatitis | Week 26 | The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Change From Baseline in Pancreatic Enzymes at Week 26 | Baseline, Week 26 | Serum Amylase (total and pancreas-derived) and lipase concentrations were measured. |
| Change From Baseline in HbA1c (Individual Doses) at Week 26 | Baseline, Week 26 | HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean in HbA1c was calculated using a REML based MMRM and adjusted by, baseline + insulin use + metformin use + treatment + time + treatment\*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline). |
| Change From Baseline in Serum Calcitonin at Week 26 | Baseline, Week 26 | Change from Baseline in Serum Calcitonin was evaluated. |
| Percentage of Participants With Allergic, Hypersensitivity Reactions | Week 26 | The percentage of Participants with Allergic and hypersensitivity reactions that were considered possibly related to study drug by the investigator are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Percentage of Participants With Injection Site Reactions | Week 26 | The percentage of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
| Number of Participants With Anti-Dulaglutide Antibodies | Baseline through Week 56 | Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 26 and 56. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. |
| Pharmacokinetics (PK): Maximum Concentration of Dulaglutide at Steady-state (Cmax,ss) | Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit | PK: Maximum Concentration of Dulaglutide at steady-state (Cmax,ss) was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9. |
| PK: Area Under the Concentration Time Curve Over a 1-week Interval of Dulaglutide at Steady-State [AUC(0-168)ss] | Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit | PK: Area Under the Concentration Time Curve over a 1-week interval of Dulaglutide at Steady-State \[AUC(0-168)ss\] was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9. |
| Number of Participants With Thyroid Treatment-Emergent Adverse Events | Week 26 | Number of Participants with Thyroid Treatment-Emergent Adverse Events were summarized. |
Countries
Brazil, France, Germany, Hungary, India, Mexico, Puerto Rico, Saudi Arabia, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo/0.75 mg Dulaglutide Participants received placebo administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week dulaglutide for 26 weeks during the OLE. | 51 |
| 0.75 mg Dulaglutide Participants received 0.75 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 0.75 mg/week for 26 weeks during the OLE. | 51 |
| 1.5 mg Dulaglutide Participants received 1.5 mg/week dulaglutide administered SC for 26 weeks during the double-blind period and open-label 1.5 mg/week for 26 weeks during the OLE. | 52 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Period | Adverse Event | 1 | 0 | 1 |
| Double-Blind Period | Lost to Follow-up | 0 | 1 | 0 |
| Double-Blind Period | Physician Decision | 1 | 0 | 0 |
| Double-Blind Period | Protocol Violation | 1 | 0 | 0 |
| Double-Blind Period | Withdrawal by Parent or Guardian | 0 | 0 | 1 |
| Double-Blind Period | Withdrawal by Subject | 1 | 1 | 0 |
| Open Label Extension (OLE) | Physician Decision | 1 | 2 | 2 |
| Open Label Extension (OLE) | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Placebo/0.75 mg Dulaglutide | 0.75 mg Dulaglutide | 1.5 mg Dulaglutide |
|---|---|---|---|---|
| Age, Continuous | 14.50 years STANDARD_DEVIATION 2.04 | 14.20 years STANDARD_DEVIATION 2.08 | 14.70 years STANDARD_DEVIATION 2.21 | 14.70 years STANDARD_DEVIATION 1.81 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 85 Participants | 26 Participants | 31 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 65 Participants | 25 Participants | 18 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 2 Participants | 2 Participants |
| Percentage of Hemoglobin A1c (HbA1c) at Baseline | 8.08 Percentage of HbA1c STANDARD_DEVIATION 1.26 | 8.14 Percentage of HbA1c STANDARD_DEVIATION 1.12 | 7.92 Percentage of HbA1c STANDARD_DEVIATION 1.27 | 8.16 Percentage of HbA1c STANDARD_DEVIATION 1.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 16 Participants | 6 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 11 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 5 Participants | 9 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 3 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 84 Participants | 25 Participants | 29 Participants | 30 Participants |
| Region of Enrollment Brazil | 16 Participants | 4 Participants | 7 Participants | 5 Participants |
| Region of Enrollment France | 4 Participants | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Germany | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Region of Enrollment India | 11 Participants | 3 Participants | 4 Participants | 4 Participants |
| Region of Enrollment Mexico | 36 Participants | 14 Participants | 12 Participants | 10 Participants |
| Region of Enrollment Puerto Rico | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Saudi Arabia | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Turkey | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United Kingdom | 5 Participants | 3 Participants | 2 Participants | 0 Participants |
| Region of Enrollment United States | 71 Participants | 22 Participants | 21 Participants | 28 Participants |
| Sex: Female, Male Female | 110 Participants | 41 Participants | 35 Participants | 34 Participants |
| Sex: Female, Male Male | 44 Participants | 10 Participants | 16 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 51 | 0 / 52 | 0 / 47 | 0 / 49 | 0 / 50 |
| other Total, other adverse events | 26 / 51 | 25 / 51 | 28 / 52 | 18 / 47 | 16 / 49 | 20 / 50 |
| serious Total, serious adverse events | 3 / 51 | 1 / 51 | 1 / 52 | 0 / 47 | 1 / 49 | 2 / 50 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses) at Week 26
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Least square (LS) mean in HbA1c was calculated using a restricted maximum likelihood (REML) based mixed-effects model for repeated measures (MMRM) and adjusted by, baseline + insulin Use + metformin Use + treatment + time + treatment\*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline).
Time frame: Baseline, Week 26
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses) at Week 26 | 0.5 percentage of HbA1C | Standard Error 0.24 |
| Pooled Dulaglutide | Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses) at Week 26 | -0.7 percentage of HbA1C | Standard Error 0.16 |
p-value: <0.00195% CI: [-1.8, -0.7]Mixed Models Analysis
Secondary
Change From Baseline in Body Mass Index (BMI) at Week 26
BMI is an estimate of body fat based on body weight divided by height squared. LS mean were calculated using a MMRM analysis and adjusted by baseline, strata, treatment, time, treatment\*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group (\< 8%, \>= 8%).
Time frame: Baseline, Week 26
Population: All randomized participants who received at least one dose of study drug and had evaluable BMI data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Body Mass Index (BMI) at Week 26 | -0.0 kilograms/square meter (kg/m^2) | Standard Error 0.21 |
| Pooled Dulaglutide | Change From Baseline in Body Mass Index (BMI) at Week 26 | -0.2 kilograms/square meter (kg/m^2) | Standard Error 0.2 |
| 1.5 mg Dulaglutide | Change From Baseline in Body Mass Index (BMI) at Week 26 | -0.1 kilograms/square meter (kg/m^2) | Standard Error 0.19 |
| Pooled Dulaglutide | Change From Baseline in Body Mass Index (BMI) at Week 26 | -0.1 kilograms/square meter (kg/m^2) | Standard Error 0.14 |
p-value: 0.68995% CI: [-0.7, 0.5]Mixed Models Analysis
p-value: 0.92495% CI: [-0.6, 0.5]Mixed Models Analysis
p-value: 0.77695% CI: [-0.6, 0.4]Mixed Models Analysis
Secondary
Change From Baseline in Fasting Blood Glucose (FBG) at Week 26
Fasting blood glucose is a test to determine how much glucose (sugar) is in a blood sample after an overnight fast. Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis and adjusted by baseline, strata, treatment, time, treatment\*time, (Type III sum of squares). Variance-Covariance structure = Unstructured (for actual value) / Unstructured (for change from baseline). Strata refer to: insulin use + metformin use + baseline HbA1c group \[ less than (\<) 8%, greater than or equal to (\>=) 8%).
Time frame: Baseline, Week 26
Population: All randomized participants who received at least one dose of study drug and had evaluable fasting blood glucose data. Only pre-rescue measurements were used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | 0.96 millimoles per liter (mmol/L) | Standard Error 0.45 |
| Pooled Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | -0.47 millimoles per liter (mmol/L) | Standard Error 0.41 |
| 1.5 mg Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | -1.54 millimoles per liter (mmol/L) | Standard Error 0.41 |
| Pooled Dulaglutide | Change From Baseline in Fasting Blood Glucose (FBG) at Week 26 | -1.03 millimoles per liter (mmol/L) | Standard Error 0.29 |
p-value: 0.02195% CI: [-2.65, -0.22]Mixed Models Analysis
p-value: <0.00195% CI: [-3.72, -1.29]Mixed Models Analysis
p-value: <0.00195% CI: [-3.03, -0.91]Mixed Models Analysis
Secondary
Change From Baseline in HbA1c (Individual Doses) at Week 26
HbA1c is a form of hemoglobin that is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean in HbA1c was calculated using a REML based MMRM and adjusted by, baseline + insulin use + metformin use + treatment + time + treatment\*time (Type III sum of squares). Variance-covariance structure = unstructured (for actual value) / unstructured (for change from baseline).
Time frame: Baseline, Week 26
Population: All randomized participants who received at least one dose of study drug and had evaluable baseline and post-baseline HbA1c.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in HbA1c (Individual Doses) at Week 26 | 0.5 percentage of HbA1c | Standard Error 0.24 |
| Pooled Dulaglutide | Change From Baseline in HbA1c (Individual Doses) at Week 26 | -0.5 percentage of HbA1c | Standard Error 0.22 |
| 1.5 mg Dulaglutide | Change From Baseline in HbA1c (Individual Doses) at Week 26 | -1.0 percentage of HbA1c | Standard Error 0.22 |
p-value: 0.00295% CI: [-1.7, -0.4]Mixed Models Analysis
p-value: <0.00195% CI: [-2.2, -0.9]Mixed Models Analysis
Secondary
Change From Baseline in Pancreatic Enzymes at Week 26
Serum Amylase (total and pancreas-derived) and lipase concentrations were measured.
Time frame: Baseline, Week 26
Population: All randomized participants who received at least one dose of study drug and had evaluable pancreatic enzymes data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase | 0.09 Units/Liter (U/L) | Standard Deviation 17.36 |
| Placebo | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Lipase | 2.23 Units/Liter (U/L) | Standard Deviation 31.99 |
| Placebo | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase, Pancreatic | 0.60 Units/Liter (U/L) | Standard Deviation 9.94 |
| Pooled Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase | 4.80 Units/Liter (U/L) | Standard Deviation 9.39 |
| Pooled Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Lipase | 4.37 Units/Liter (U/L) | Standard Deviation 8.28 |
| Pooled Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase, Pancreatic | 1.77 Units/Liter (U/L) | Standard Deviation 4.72 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase, Pancreatic | 2.90 Units/Liter (U/L) | Standard Deviation 6.1 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase | 6.50 Units/Liter (U/L) | Standard Deviation 8.91 |
| 1.5 mg Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Lipase | 3.88 Units/Liter (U/L) | Standard Deviation 6.63 |
| Pooled Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase | 5.64 Units/Liter (U/L) | Standard Deviation 9.15 |
| Pooled Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Lipase | 4.12 Units/Liter (U/L) | Standard Deviation 7.47 |
| Pooled Dulaglutide | Change From Baseline in Pancreatic Enzymes at Week 26 | Serum Amylase, Pancreatic | 2.32 Units/Liter (U/L) | Standard Deviation 5.45 |
Secondary
Change From Baseline in Serum Calcitonin at Week 26
Change from Baseline in Serum Calcitonin was evaluated.
Time frame: Baseline, Week 26
Population: All randomized participants who received at least one dose of study drug and had evaluable serum calcitonin data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Serum Calcitonin at Week 26 | 0.38 nanograms per liter (ng/L) | Standard Deviation 1.7 |
| Pooled Dulaglutide | Change From Baseline in Serum Calcitonin at Week 26 | 0.28 nanograms per liter (ng/L) | Standard Deviation 0.72 |
| 1.5 mg Dulaglutide | Change From Baseline in Serum Calcitonin at Week 26 | 0.10 nanograms per liter (ng/L) | Standard Deviation 0.5 |
| Pooled Dulaglutide | Change From Baseline in Serum Calcitonin at Week 26 | 0.19 nanograms per liter (ng/L) | Standard Deviation 0.62 |
Secondary
Number of Participants With Adjudicated Pancreatitis
The number of participants with pancreatitis confirmed by adjudication is summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Week 26
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Adjudicated Pancreatitis | 0 participants |
| Pooled Dulaglutide | Number of Participants With Adjudicated Pancreatitis | 0 participants |
| 1.5 mg Dulaglutide | Number of Participants With Adjudicated Pancreatitis | 0 participants |
| Pooled Dulaglutide | Number of Participants With Adjudicated Pancreatitis | 0 participants |
Secondary
Number of Participants With Anti-Dulaglutide Antibodies
Dulaglutide anti-drug antibodies (ADA) were assessed at baseline, Weeks 26 and 56. A participant was considered to have treatment-emergent (TE) dulaglutide ADAs if the participant had at least 1 titer that was TE relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement.
Time frame: Baseline through Week 56
Population: All randomized participants who received at least 1 dose of study drug and had at least one post-baseline Dulaglutide ADA test result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Anti-Dulaglutide Antibodies | 3 participants |
| Pooled Dulaglutide | Number of Participants With Anti-Dulaglutide Antibodies | 3 participants |
| 1.5 mg Dulaglutide | Number of Participants With Anti-Dulaglutide Antibodies | 3 participants |
Secondary
Number of Participants With Thyroid Treatment-Emergent Adverse Events
Number of Participants with Thyroid Treatment-Emergent Adverse Events were summarized.
Time frame: Week 26
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Thyroid Treatment-Emergent Adverse Events | 0 Participants |
| Pooled Dulaglutide | Number of Participants With Thyroid Treatment-Emergent Adverse Events | 0 Participants |
| 1.5 mg Dulaglutide | Number of Participants With Thyroid Treatment-Emergent Adverse Events | 0 Participants |
| Pooled Dulaglutide | Number of Participants With Thyroid Treatment-Emergent Adverse Events | 0 Participants |
Secondary
Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia
Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia was summarized.
Time frame: Week 26
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia | 17.6 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia | 3.9 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia | 1.9 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants Requiring Rescue for Severe, Persistent Hyperglycemia | 2.9 percentage of participants |
Secondary
Percentage of Participants With Allergic, Hypersensitivity Reactions
The percentage of Participants with Allergic and hypersensitivity reactions that were considered possibly related to study drug by the investigator are presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Week 26
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Allergic, Hypersensitivity Reactions | 2.0 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants With Allergic, Hypersensitivity Reactions | 3.9 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants With Allergic, Hypersensitivity Reactions | 1.9 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants With Allergic, Hypersensitivity Reactions | 2.9 percentage of participants |
Secondary
Percentage of Participants With HbA1c ≤7.0%
The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
Time frame: Week 26
Population: All randomized participants who received at least 1 dose of study drug and had evaluable baseline and post-baseline HbA1c.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With HbA1c ≤7.0% | 18.42 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants With HbA1c ≤7.0% | 60.00 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants With HbA1c ≤7.0% | 53.19 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants With HbA1c ≤7.0% | 56.52 percentage of participants |
p-value: <0.00195% CI: [3.491, 34.902]Regression, Logistic
p-value: <0.00195% CI: [3.653, 37.253]Regression, Logistic
p-value: <0.00195% CI: [4.163, 30.932]Regression, Logistic
Secondary
Percentage of Participants With Injection Site Reactions
The percentage of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Week 26
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Injection Site Reactions | 9.8 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants With Injection Site Reactions | 9.8 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants With Injection Site Reactions | 7.7 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants With Injection Site Reactions | 8.7 percentage of participants |
Secondary
Percentage of Participants With Self-Reported Events of Hypoglycemia
Summary and analysis of Incidence of all hypoglycemia with Plasma Glucose \<54mg/dL.
Time frame: Week 26
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Self-Reported Events of Hypoglycemia | 1.96 percentage of participants |
| Pooled Dulaglutide | Percentage of Participants With Self-Reported Events of Hypoglycemia | 3.92 percentage of participants |
| 1.5 mg Dulaglutide | Percentage of Participants With Self-Reported Events of Hypoglycemia | 3.85 percentage of participants |
Secondary
Pharmacokinetics (PK): Maximum Concentration of Dulaglutide at Steady-state (Cmax,ss)
PK: Maximum Concentration of Dulaglutide at steady-state (Cmax,ss) was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9.
Time frame: Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Pharmacokinetics (PK): Maximum Concentration of Dulaglutide at Steady-state (Cmax,ss) | 31 nanograms per milliliter (ng/mL) |
| Pooled Dulaglutide | Pharmacokinetics (PK): Maximum Concentration of Dulaglutide at Steady-state (Cmax,ss) | 62 nanograms per milliliter (ng/mL) |
Secondary
PK: Area Under the Concentration Time Curve Over a 1-week Interval of Dulaglutide at Steady-State [AUC(0-168)ss]
PK: Area Under the Concentration Time Curve over a 1-week interval of Dulaglutide at Steady-State \[AUC(0-168)ss\] was derived by a population pharmacokinetics approach. As part of addendum, additional PK samples were taken at week 9.
Time frame: Week 9: pre-dose,1 to 12 hours post dose and 24 to 96 hours post dose; Week 13: predose and 1 to 12 hours post dose; Week 26: predose; Week 39: up to 2 days postdose; Week 52 and Week 56: PK sample can be taken at any time during the visit
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | PK: Area Under the Concentration Time Curve Over a 1-week Interval of Dulaglutide at Steady-State [AUC(0-168)ss] | 4170 nanogram*hour per milliliter (ng*h/ mL) |
| Pooled Dulaglutide | PK: Area Under the Concentration Time Curve Over a 1-week Interval of Dulaglutide at Steady-State [AUC(0-168)ss] | 8350 nanogram*hour per milliliter (ng*h/ mL) |