Healthy
Conditions
Brief summary
The purpose of this study is to determine how the body handles LY3185643 and rGlucagon and what effects LY3185643 and rGlucagon have on the body. This study will also help to determine if LY3185643 is safe and well-tolerated. This study will last at least 35 days, not including screening.
Interventions
DRUGLY3185643
Administered SC
DRUGrGlucagon
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy as determined by medical history and physical examination * Body mass index of 18.0 to 30.0 kilograms per square meter (kg/m²)
Exclusion criteria
* Have participated, within the last 30 days, in a clinical trial involving an investigational product * Known allergies to LY3185643 or rGlucagon, related compounds, or any components of the formulation * History or electrocardiogram (ECG) evidence of heart block, or any abnormality in the 12-lead ECG * Abnormal blood pressure * History of recurring symptomatic postural hypotension irrespective of the decrease in blood pressure, or asymptomatic postural hypotension at screening as defined as a decrease in systolic blood pressure greater than or equal to (≥) 20 millimeter of Mercury (mm Hg) within 3 minutes when changing from supine to standing position * History of vasovagal response such as fainting * History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational product; or of interfering with the interpretation of data * History of/current insulinoma and/or pheochromocytoma * Have used systemic glucocorticoids within 3 months before entry into the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 0 (pre-dose), 15, 30, 60, 120 and 180 minutes post-dose | Maximum observed plasma concentration (Cmax) was assessed for LY3185643 and rGlucagon. |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 0 (pre-dose), 15, 30, 60, 120 and 180 minutes post-dose | Area under the concentration versus time curve from zero to infinity (AUC0-inf) was assessed for LY3185643 and rGlucagon. |
| Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | -5, 0 (pre-dose), 5, 10, 15, 22, 30, 45, 60, 75, 90, 105, 120, 150, 180 minutes post-dose | Cmax was assessed for LY3185643 and rGlucagon. |
| Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | -5, 0 (predose), 5, 15, 30, 60 and 120 minutes post-dose | Cmax was assessed for C-peptide of LY3185643 and rGlucagon |
| Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | -5, 0 (pre-dose), 5, 10, 15, 22, 30, 45, 60, 75, 90, 105, 120, 150, 180 minutes post-dose | Area under the concentration versus time curve from time zero to 3 hours \[AUC (0-3)\] was assessed for LY3185643 and rGlucagon. |
| Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | -5, 0 (pre-dose), 5, 15, 30, 60 and 120 minutes post-dose | Area under the concentration versus time curve from time zero to 3 hours \[AUC (0-3)\] was assessed for C-peptide of LY3185643 and rGlucagon. |
Countries
Singapore
Participant flow
Pre-assignment details
Crossover study with three periods. Each participant received up to 3 doses of study drug (rGlucagon and/or LY3185643) in a dosing day as per the dosing sequence in each period with 7 to 12 days washout period.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A (Sequence 1,9,7: 6,4,8:5,3,2) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 1-9-7 in Treatment Period 1, Dosing Sequence: 6-4-8 in Treatment Period 2 and Dosing Sequence: 5-3-2 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 3 |
| Cohort B (Sequence 2,7,8: 4,5,9: 6,1,3 ) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 2-7-8 in Treatment Period 1, Dosing Sequence: 4-5-9 in Treatment Period 2 and Dosing Sequence: 6-1-3 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 2 |
| Cohort C (Sequence 3,8,9: 5,6,7: 4,2,1) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 3-8-9 in Treatment Period 1, Dosing Sequence: 5-6-7 in Treatment Period 2 and Dosing Sequence: 4-2-1 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 3 |
| Cohort D (Sequence 4,6,2: 3,9,1: 8,7,5) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 4-6-2 in Treatment Period 1, Dosing Sequence: 3-9-1 in Treatment Period 2 and Dosing Sequence: 8-7-5 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 3 |
| Cohort E (Sequence 5,4,3: 1,7,2: 9,8,6) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 5-4-3 in Treatment Period 1, Dosing Sequence: 1-7-2 in Treatment Period 2 and Dosing Sequence: 9-8-6 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 2 |
| Cohort F (Sequence 6,5,1: 2,8,3: 7,9,4) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 6-5-1 in Treatment Period 1, Dosing Sequence: 2-8-3 in Treatment Period 2 and Dosing Sequence: 7-9-4 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 3 |
| Cohort G (Sequence 7,1,4: 9,2,6: 9,2,6) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 7-1-4 in Treatment Period 1, Dosing Sequence: 9-2-6 in Treatment Period 2 and Dosing Sequence: 9-2-6 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 2 |
| Cohort H (Sequence 8,2,5: 7,3,4: 1,6,9) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 8-2-5 in Treatment Period 1, Dosing Sequence: 7-3-4 in Treatment Period 2 and Dosing Sequence: 1-6-9 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 3 |
| Cohort I (Sequence 9,3,6: 8,1,5: 2,4,7) ) LY3185643 and rGlucagon were administered as single SC doses with Dosing Sequence 9-3-6 in Treatment Period 1, Dosing Sequence: 8-1-5 in Treatment Period 2 and Dosing Sequence: 2-4-7 in Treatment Period 3.
Dose assignment was: Dose 1 = 10 μg LY3185643; Dose 2 = 25 μg LY3185643; Dose 3 = 50 μg LY3185643; Dose 4 = 100 μg LY3185643; Dose 5 = 200 μg LY3185643; Dose 6 = 10 μg rGlucagon; Dose 7 = 25 μg rGlucagon; Dose 8 = 50 μg rGlucagon; Dose 9 = 200 μg rGlucagon. | 2 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 | Adverse Event | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Scheduling Conflicts | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 2 | Scheduling Conflicts | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort B (Sequence 2,7,8: 4,5,9: 6,1,3 ) | Cohort C (Sequence 3,8,9: 5,6,7: 4,2,1) | Cohort D (Sequence 4,6,2: 3,9,1: 8,7,5) | Cohort E (Sequence 5,4,3: 1,7,2: 9,8,6) | Cohort A (Sequence 1,9,7: 6,4,8:5,3,2) | Cohort F (Sequence 6,5,1: 2,8,3: 7,9,4) | Cohort G (Sequence 7,1,4: 9,2,6: 9,2,6) | Cohort H (Sequence 8,2,5: 7,3,4: 1,6,9) | Cohort I (Sequence 9,3,6: 8,1,5: 2,4,7) ) |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 23 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Singapore | 23 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 23 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 2 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 23 | 0 / 21 | 0 / 22 | 0 / 22 | 0 / 21 | 0 / 21 | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 3 / 20 | 3 / 23 | 3 / 21 | 5 / 22 | 4 / 22 | 2 / 21 | 1 / 21 | 2 / 22 | 2 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 23 | 0 / 21 | 0 / 22 | 0 / 22 | 0 / 21 | 0 / 21 | 0 / 22 | 0 / 20 |
Outcome results
Primary
Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon
Area under the concentration versus time curve from time zero to 3 hours \[AUC (0-3)\] was assessed for LY3185643 and rGlucagon.
Time frame: -5, 0 (pre-dose), 5, 10, 15, 22, 30, 45, 60, 75, 90, 105, 120, 150, 180 minutes post-dose
Population: All randomized participants who received at least one dose of study drug (LY3185643, C-peptide) and with a baseline and at least 1 postbaseline measurement for each dose with evaluable LY3185643 and rGlucagon PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 1.46 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 7.52 |
| 25 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 18.9 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 15.3 |
| 50 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 29.7 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 21.1 |
| 100 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 45.1 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 27.1 |
| 200 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 71.5 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 37.8 |
| 10 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 0.594 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 11.9 |
| 25 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 7.74 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 15.6 |
| 50 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 12.1 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 14.4 |
| 200 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of Blood Glucose of LY3185643 and rGlucagon | 24.0 milligram*hour per deciliter (mg*hr/dL) | Standard Deviation 15.8 |
Primary
Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon
Area under the concentration versus time curve from time zero to 3 hours \[AUC (0-3)\] was assessed for C-peptide of LY3185643 and rGlucagon.
Time frame: -5, 0 (pre-dose), 5, 15, 30, 60 and 120 minutes post-dose
Population: All randomized participants who received at least one dose of study drug (C-peptide of LY3185643 and rGlucagon) and with a baseline and at least 1 postbaseline measurement for each dose with evaluable LY3185643 and rGlucagon PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | 25.0 picomole*hour per liter (pmol*h/L) | Standard Deviation 60.5 |
| 25 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | 246 picomole*hour per liter (pmol*h/L) | Standard Deviation 194 |
| 50 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | 354 picomole*hour per liter (pmol*h/L) | Standard Deviation 388 |
| 100 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | 669 picomole*hour per liter (pmol*h/L) | Standard Deviation 441 |
| 200 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | 1170 picomole*hour per liter (pmol*h/L) | Standard Deviation 529 |
| 10 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | -28.3 picomole*hour per liter (pmol*h/L) | Standard Deviation 82.2 |
| 25 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | 82.1 picomole*hour per liter (pmol*h/L) | Standard Deviation 130 |
| 50 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | 167 picomole*hour per liter (pmol*h/L) | Standard Deviation 162 |
| 200 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Area Under the Concentration Time Curve (AUC) of C-Peptide of LY3185643 and rGlucagon | 626 picomole*hour per liter (pmol*h/L) | Standard Deviation 325 |
Primary
Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon
Cmax was assessed for LY3185643 and rGlucagon.
Time frame: -5, 0 (pre-dose), 5, 10, 15, 22, 30, 45, 60, 75, 90, 105, 120, 150, 180 minutes post-dose
Population: All randomized participants who received at least one dose of study drug (LY3185643, rGlucagon) and with a baseline and at least 1 postbaseline measurement for each dose with evaluable LY3185643 and rGlucagon PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 5.54 milligram per deciliter (mg/dL) | Standard Deviation 2.66 |
| 25 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 15.1 milligram per deciliter (mg/dL) | Standard Deviation 9.94 |
| 50 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 24.0 milligram per deciliter (mg/dL) | Standard Deviation 16.6 |
| 100 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 37.1 milligram per deciliter (mg/dL) | Standard Deviation 20.6 |
| 200 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 53.2 milligram per deciliter (mg/dL) | Standard Deviation 17.7 |
| 10 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 4.37 milligram per deciliter (mg/dL) | Standard Deviation 3.39 |
| 25 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 12.5 milligram per deciliter (mg/dL) | Standard Deviation 11.1 |
| 50 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 16.9 milligram per deciliter (mg/dL) | Standard Deviation 11.4 |
| 200 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of Blood Glucose of LY3185643 and rGlucagon | 38.1 milligram per deciliter (mg/dL) | Standard Deviation 13.9 |
Primary
Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon
Cmax was assessed for C-peptide of LY3185643 and rGlucagon
Time frame: -5, 0 (predose), 5, 15, 30, 60 and 120 minutes post-dose
Population: All randomized participants who received at least one dose of study drug (C-peptide of LY3185643 and rGlucagon) and with a baseline and at least 1 postbaseline measurement for each dose with evaluable LY3185643 and rGlucagon PD data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 10 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 50.2 picomole per liter (pmol/L) | Standard Deviation 44.7 |
| 25 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 201 picomole per liter (pmol/L) | Standard Deviation 168 |
| 50 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 324 picomole per liter (pmol/L) | Standard Deviation 330 |
| 100 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 555 picomole per liter (pmol/L) | Standard Deviation 387 |
| 200 ug LY3185643 | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 969 picomole per liter (pmol/L) | Standard Deviation 451 |
| 10 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 25.4 picomole per liter (pmol/L) | Standard Deviation 34.1 |
| 25 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 119 picomole per liter (pmol/L) | Standard Deviation 98.9 |
| 50 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 218 picomole per liter (pmol/L) | Standard Deviation 154 |
| 200 ug rGlucagon | Pharmacodynamics (PD): Change From Baseline in Maximum Concentration (Cmax) of C-peptide of LY3185643 and rGlucagon | 577 picomole per liter (pmol/L) | Standard Deviation 292 |
Primary
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon
Area under the concentration versus time curve from zero to infinity (AUC0-inf) was assessed for LY3185643 and rGlucagon.
Time frame: 0 (pre-dose), 15, 30, 60, 120 and 180 minutes post-dose
Population: All randomized participants who received at least one dose of study drug (LY3185643, rGlucagon) and with a baseline and at least 1 postbaseline measurement for each dose with evaluable LY3185643 and rGlucagon PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 ug LY3185643 | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 356 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 30 |
| 25 ug LY3185643 | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 1200 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 21 |
| 50 ug LY3185643 | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 2230 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 21 |
| 100 ug LY3185643 | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 4430 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 21 |
| 200 ug LY3185643 | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 9120 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 17 |
| 10 ug rGlucagon | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | NA picogram*hour per milliliter (pg*hr/mL) | — |
| 25 ug rGlucagon | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 189 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 57 |
| 50 ug rGlucagon | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 249 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 24 |
| 200 ug rGlucagon | Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3185643 and rGlucagon | 764 picogram*hour per milliliter (pg*hr/mL) | Geometric Coefficient of Variation 26 |
Primary
Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon
Maximum observed plasma concentration (Cmax) was assessed for LY3185643 and rGlucagon.
Time frame: 0 (pre-dose), 15, 30, 60, 120 and 180 minutes post-dose
Population: All randomized participants who received at least one dose of study drug (LY3185643, rGlucagon) and with a baseline and at least 1 postbaseline measurement for each dose with evaluable LY3185643 and rGlucagon PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 10 ug LY3185643 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 191 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 49 |
| 25 ug LY3185643 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 658 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 36 |
| 50 ug LY3185643 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 1110 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 40 |
| 100 ug LY3185643 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 2010 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 40 |
| 200 ug LY3185643 | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 3830 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 38 |
| 10 ug rGlucagon | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 53.7 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 31 |
| 25 ug rGlucagon | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 204 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 70 |
| 50 ug rGlucagon | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 283 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 44 |
| 200 ug rGlucagon | Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY3185643 and rGlucagon | 897 picogram per milliliter (pg/mL) | Geometric Coefficient of Variation 49 |