Diabetes Mellitus, Type 1
Conditions
Brief summary
This study involves taking a single dose of 100 milligrams (mg) or 300 mg LY2409021 or placebo (an inactive medicine) taken as up to 3 capsules by mouth. The study will evaluate if this drug will reduce the amount of insulin a type 1 diabetic needs over 24 hours. This study includes a 7-day hospitalization period at the clinical research unit (CRU) and will involve screening within 30 days of the start of the study as well as telephone consultations within 5 days after discharge from the CRU.
Interventions
DRUGLY2409021
Administered orally
DRUGPlacebo
Administered orally
DRUGGlucagon
Administered via intramuscular injection
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have had type 1 diabetes mellitus (T1DM) based on the World Health Organization classification for at least 1 year and have a daily insulin dose ≤1.5 international units (IU) per kilogram (kg) of body weight * Have a glycated hemoglobin A1c (HbA1c) of no greater than 9.0% as measured at screening * Have a body mass index (BMI) ≥19.0 and ≤35.0 kilograms per meter squared (kg/m\^2) * Have given written informed consent approved by Lilly
Exclusion criteria
* Received any oral or injectable medication intended for the treatment of diabetes mellitus other than insulins in the 3 months prior to screening * Have had more than 1 episode of severe hypoglycemia within 3 months prior to entry into the study, or are currently diagnosed as having hypoglycemia unawareness * Are pregnant or intend to become pregnant during the course of the study * Women who are breastfeeding * Have a history of stroke, myocardial infarction, heart failure, unstable angina, or a coronary revascularization procedure within 6 months of screening * Have fasting triglycerides \>500 milligrams per deciliter (mg/dL) (5.65 millimoles per liter \[mmol/L\]) * Have obvious clinical signs, symptoms, or laboratory evidence of liver disease (alanine transaminase \[ALT\] or aspartate transaminase \[AST\] greater than 2 times the upper limit of normal at screening) * Have a history of renal transplantation or are currently receiving renal dialysis or have a screening creatinine \>2.0 mg/dL (177 micromoles per liter \[μmol/L\]) * Have had any other disease, illness, or condition (including known diabetic autonomic neuropathy, drug or alcohol abuse, or psychiatric disorder) within the 6 months prior to screening that precludes the participant from following and completing the study or could increase their risk for hypoglycemia, according to the investigator's judgment * Are currently enrolled in, have completed, or have discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose | Baseline (Day 1), Day 2 | The mean absolute change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | Predose (Day 2) through 120 hours postdose (Day 7) | — |
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2409021 | Predose (Day 2) through 120 hours postdose (Day 7) | Exposure in terms of AUC of LY2409021 from time 0 extrapolated to infinity (AUCinf) is reported. |
| Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose During Drug Washout Period | Baseline (Day 1), Day 3 up to Day 6 | Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis. |
| Pharmacodynamics: Percentage Change From Baseline to Day 2 in 24-hour Insulin | Baseline (Day 1), Day 2 | The percentage change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported. |
| Pharmacodynamics: Maximum Concentration (Cmax) of Glucose Concentration After 1 Milligram (mg) Glucagon Injection on Day 3 | Day 3 | The Cmax of glucose following a single dose of glucagon (1 mg) administered via an intramuscular injection is reported. |
| Pharmacodynamics: Area Under the Glucose Concentration Curve After a Single Dose of Glucagon on Day 3 | Day 3 | Area under the glucose concentration curve from time 0 through 2 hours after a single dose of glucagon (1 milligram) administered via an intramuscular injection is reported. |
| Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose Needed to Maintain Euglycemia | Baseline (Day 1), Day 3 up to Day 6 | Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 100 mg LY2409021 LY2409021: 100 milligrams (mg), 1 capsule, administered as a single oral dose on Day 2.
Placebo: 2 capsules, administered as a single oral dose on Day 2.
Glucagon: 1 mg administered via intramuscular injection on Day 3. | 8 |
| 300 mg LY2409021 LY2409021: 300 milligrams (mg), 3 capsules (3 X 100-mg capsules), administered as a single oral dose on Day 2.
Glucagon: 1 mg administered via intramuscular injection on Day 3. | 8 |
| Placebo Placebo: 3 capsules administered as a single oral dose on Day 2.
Glucagon: 1 milligram (mg) administered via intramuscular injection on Day 3. | 4 |
| Total | 20 |
Baseline characteristics
| Characteristic | 100 mg LY2409021 | 300 mg LY2409021 | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 38.6 years STANDARD_DEVIATION 12.8 | 47.1 years STANDARD_DEVIATION 5.7 | 43.3 years STANDARD_DEVIATION 10.6 | 43.0 years STANDARD_DEVIATION 10.3 |
| Race/Ethnicity, Customized White | 8 Participants | 8 Participants | 4 Participants | 20 Participants |
| Region of Enrollment Germany | 8 Participants | 8 Participants | 4 Participants | 20 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 4 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 6 / 8 | 4 / 4 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 4 |
Outcome results
Primary
Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose
The mean absolute change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.
Time frame: Baseline (Day 1), Day 2
Population: All participants who received a dose of LY2409021 or placebo and had evaluable 24-hour insulin data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 mg LY2409021 | Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose | 1.85 insulin units | Standard Deviation 7.15 |
| 300 mg LY2409021 | Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose | 0.80 insulin units | Standard Deviation 9.63 |
| Placebo | Pharmacodynamics: Change From Baseline to Day 2 in 24-hour Insulin Dose | 7.69 insulin units | Standard Deviation 2.99 |
Comparison: The mean change on Day 2 from Day 1 in the 24-hour insulin dose for the placebo group was subtracted from each participant's change on Day 2 from Day 1 in the 24-hour insulin dose. This placebo adjusted 24-hour insulin dose was compared within the 100-mg LY2409021 dose group using a 1 sample t-test.p-value: 0.054295% CI: [-11.82, 0.14]t-test, 1 sided
Comparison: The mean change on Day 2 from Day 1 in the 24-hour insulin dose for the placebo group was subtracted from each participant's change on Day 2 from Day 1 in the 24-hour insulin dose. This placebo adjusted 24-hour insulin dose was compared within the 300-mg LY2409021 dose group.p-value: 0.082695% CI: [-14.95, 1.16]t-test, 1 sided
Secondary
Pharmacodynamics: Area Under the Glucose Concentration Curve After a Single Dose of Glucagon on Day 3
Area under the glucose concentration curve from time 0 through 2 hours after a single dose of glucagon (1 milligram) administered via an intramuscular injection is reported.
Time frame: Day 3
Population: All participants who received a dose of LY2409021 or placebo and had evaluable post-glucagon injection glucose concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 100 mg LY2409021 | Pharmacodynamics: Area Under the Glucose Concentration Curve After a Single Dose of Glucagon on Day 3 | 15534.3 milligrams * minutes per deciliter | Geometric Coefficient of Variation 21 |
| 300 mg LY2409021 | Pharmacodynamics: Area Under the Glucose Concentration Curve After a Single Dose of Glucagon on Day 3 | 14885.5 milligrams * minutes per deciliter | Geometric Coefficient of Variation 16 |
| Placebo | Pharmacodynamics: Area Under the Glucose Concentration Curve After a Single Dose of Glucagon on Day 3 | 20189.7 milligrams * minutes per deciliter | Geometric Coefficient of Variation 9 |
Comparison: Statistical analysis of the effect of LY2409021 treatment on area under the glucose concentration curve from time 0 to 2 hours postdose following an intramuscular injection of glucagon (1 milligram).p-value: 0.027895% CI: [-8256, -590]t-test, 2 sided
Comparison: Statistical analysis of the effect of LY2409021 treatment on area under the glucose concentration curve from time 0 to 2 hours postdose following an intramuscular injection of glucagon (1 milligram).p-value: 0.004695% CI: [-8371, -2004]t-test, 2 sided
Secondary
Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose During Drug Washout Period
Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis.
Time frame: Baseline (Day 1), Day 3 up to Day 6
Population: This outcome measure was not analyzed.
Secondary
Pharmacodynamics: Change From Baseline in 24 Hour Insulin Dose Needed to Maintain Euglycemia
Data were not captured, and, therefore, this outcome measure was not analyzed. Zero participants were included in the analysis.
Time frame: Baseline (Day 1), Day 3 up to Day 6
Population: This outcome measure was not analyzed.
Secondary
Pharmacodynamics: Maximum Concentration (Cmax) of Glucose Concentration After 1 Milligram (mg) Glucagon Injection on Day 3
The Cmax of glucose following a single dose of glucagon (1 mg) administered via an intramuscular injection is reported.
Time frame: Day 3
Population: All participants who received a dose of LY2409021 or placebo and had evaluable post-glucagon injection glucose concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 100 mg LY2409021 | Pharmacodynamics: Maximum Concentration (Cmax) of Glucose Concentration After 1 Milligram (mg) Glucagon Injection on Day 3 | 154.9 milligrams per deciliter | Geometric Coefficient of Variation 19 |
| 300 mg LY2409021 | Pharmacodynamics: Maximum Concentration (Cmax) of Glucose Concentration After 1 Milligram (mg) Glucagon Injection on Day 3 | 141.3 milligrams per deciliter | Geometric Coefficient of Variation 19 |
| Placebo | Pharmacodynamics: Maximum Concentration (Cmax) of Glucose Concentration After 1 Milligram (mg) Glucagon Injection on Day 3 | 201.8 milligrams per deciliter | Geometric Coefficient of Variation 11 |
Comparison: Statistical analysis of the effect of LY2409021 treatment on peak glucose concentration after an intramuscular injection of glucagon (1 milligram).p-value: 0.018795% CI: [-82, -9]t-test, 2 sided
Comparison: Statistical analysis of the effect of LY2409021 treatment on peak glucose concentration after an intramuscular injection of glucagon (1 milligram).p-value: 0.004895% CI: [-96, -23]t-test, 2 sided
Secondary
Pharmacodynamics: Percentage Change From Baseline to Day 2 in 24-hour Insulin
The percentage change in total insulin dose over 24 hours (Day 2, 24-hour insulin dose - Day 1, 24-hour insulin dose) is reported.
Time frame: Baseline (Day 1), Day 2
Population: All participants who received a dose of LY2409021 or placebo and had evaluable 24-hour insulin data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 100 mg LY2409021 | Pharmacodynamics: Percentage Change From Baseline to Day 2 in 24-hour Insulin | 5.71 percentage of insulin units | Standard Deviation 19.9 |
| 300 mg LY2409021 | Pharmacodynamics: Percentage Change From Baseline to Day 2 in 24-hour Insulin | 3.12 percentage of insulin units | Standard Deviation 18.34 |
| Placebo | Pharmacodynamics: Percentage Change From Baseline to Day 2 in 24-hour Insulin | 22.75 percentage of insulin units | Standard Deviation 22.2 |
Comparison: Analysis was performed using the percent change in insulin dose, which takes into account absolute differences in individual insulin doses. The mean percent change on Day 2 from Day 1 in the 24-hour insulin dose for the placebo group was subtracted from each participant's percent change on Day 2 from Day 1 in the 24-hour insulin dose. This placebo adjusted 24-hour insulin dose was compared within the 100-mg LY2409021 dose group using a 1 sample t-test.p-value: 0.04695% CI: [-33.7, -0.4]t-test, 1 sided
Comparison: Analysis was performed using the percent change in insulin dose, which takes into account absolute differences in individual insulin doses. The mean percent change on Day 2 from Day 1 in the 24-hour insulin dose for the placebo group was subtracted from each participant's percent change on Day 2 from Day 1 in the 24-hour insulin dose. This placebo adjusted 24-hour insulin dose was compared within the 300-mg LY2409021 dose group using a 1 sample t-test.p-value: 0.019295% CI: [-35, -4.3]t-test, 1 sided
Secondary
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2409021
Exposure in terms of AUC of LY2409021 from time 0 extrapolated to infinity (AUCinf) is reported.
Time frame: Predose (Day 2) through 120 hours postdose (Day 7)
Population: All participants who received a dose of LY2409021 and had evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 100 mg LY2409021 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2409021 | 209000 nanograms * hours per milliliter | Geometric Coefficient of Variation 30 |
| 300 mg LY2409021 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY2409021 | 506000 nanograms * hours per milliliter | Geometric Coefficient of Variation 22 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021
Time frame: Predose (Day 2) through 120 hours postdose (Day 7)
Population: All participants who received a dose of LY2409021 and had evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 100 mg LY2409021 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | 2620 nanograms per milliliter | Geometric Coefficient of Variation 23 |
| 300 mg LY2409021 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2409021 | 6090 nanograms per milliliter | Geometric Coefficient of Variation 23 |