Healthy Volunteers
Conditions
Brief summary
This study looks at the amount of LY2605541 in the body after it is injected under the skin. The study has 3 periods, each lasting 10 days. Each participant will receive one injection in each period. At least 14 days will pass between each injection.
Interventions
DRUGLY2605541
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
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy males or females, as determined by medical history and physical examination * A body mass index of 18.5 to 30 kilograms per meter square (kg/m\^2)
Exclusion criteria
* Have a history or presence of 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 study medication; or of interfering with the interpretation of data * Are women with a positive pregnancy test or are women who are lactating * Intend to use over-the-counter medication within 7 days prior to dosing or prescription medication within 14 days prior to dosing (apart from contraceptive medication, vitamin/mineral supplements, occasional acetaminophen, and/or hormone replacement therapy) * Have donated blood of more than 500 milliliters (mL) within the last month * Have an average weekly alcohol intake that exceeds 21 units per week (for males) and 14 units per week (for females) * Are excessive consumers of xanthines (more than 10 cups of tea, coffee, cola, or hot chocolate per day) * Have a fasting blood glucose (BG) \>110 milligrams per deciliter (mg/dL) (6.1 millimoles per liter \[mmol/L\]) * Currently smoke more than 10 cigarettes per day, or are unwilling to refrain from smoking for 72 hours prior to each dosing occasion and during confinement
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of LY2605541 | Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours post dose in each period | LY2605541 exposure in terms of AUC from time 0 extrapolated to infinity (AUC\[0-inf\]) is summarized for each PEG source (LY1, LY2, or LY3). |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY2605541 | Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours post dose in each period | The maximum observed drug concentration (Cmax) of LY2605541 is summarized for each PEG source (LY1, LY2, or LY3). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucodynamics: Maximum Glucose Infusion Rate (Rmax) | Predose and up to 24 hours post dose in each period | The maximum observed glucose infusion rate following LY2605541 injection is summarized for each PEG source (LY1, LY2, or LY3). |
| Glucodynamics: Total Amount of Glucose Infused (Gtot) | Predose and up to 24 hours post dose in each period | The total amount of glucose infused following LY2605541 injection is summarized for each PEG source (LY1, LY2, or LY3). |
Countries
United States
Participant flow
Pre-assignment details
LY2605541 was manufactured using the 3 different polyethylene glycol (PEG) sources (referred to as Source 1 \[LY1\], Source 2 \[LY2\], and Source 3 \[LY3\]). Participants were randomized to 1 of 6 treatment sequences and received a single injection of LY1, LY2, or LY3 on Day 1 of each of 3 treatment periods according to their assigned treatment sequence.
Participants by arm
| Arm | Count |
|---|---|
| 0.5 U/kg LY2605541 Participants randomized to receive a single, SC injection of 0.5 U/kg LY2605541 using 3 different PEG sources on Day 1 of each of 3 treatment periods, according to their assigned treatment sequence. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 1 | Sponsor Decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 3 | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
| Washout Period 2 (at Least 14 Days) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 0.5 U/kg LY2605541 |
|---|---|
| Age, Continuous | 37.6 years STANDARD_DEVIATION 9.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 18 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 13 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 | 4 / 17 | 6 / 17 | 3 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 | 0 / 17 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of LY2605541
LY2605541 exposure in terms of AUC from time 0 extrapolated to infinity (AUC\[0-inf\]) is summarized for each PEG source (LY1, LY2, or LY3).
Time frame: Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours post dose in each period
Population: Participants who received at least 1 dose of LY2605541 and had evaluable LY2605541 concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 U/kg LY2605541 (LY1) | Pharmacokinetics: Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of LY2605541 | 128000 picomoles times hours per liter | Geometric Coefficient of Variation 23 |
| 0.5 U/kg LY2605541 (LY2) | Pharmacokinetics: Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of LY2605541 | 145000 picomoles times hours per liter | Geometric Coefficient of Variation 22 |
| 0.5 U/kg LY2605541 (LY3) | Pharmacokinetics: Area Under the Concentration Time Curve From Zero to Infinity (AUC[0-∞]) of LY2605541 | 135000 picomoles times hours per liter | Geometric Coefficient of Variation 18 |
Primary
Pharmacokinetics: Maximum Concentration (Cmax) of LY2605541
The maximum observed drug concentration (Cmax) of LY2605541 is summarized for each PEG source (LY1, LY2, or LY3).
Time frame: Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours post dose in each period
Population: Participants who received at least 1 dose of LY2605541 and had evaluable LY2605541 concentration data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 U/kg LY2605541 (LY1) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2605541 | 1980 picomoles per liter | Geometric Coefficient of Variation 39 |
| 0.5 U/kg LY2605541 (LY2) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2605541 | 2490 picomoles per liter | Geometric Coefficient of Variation 35 |
| 0.5 U/kg LY2605541 (LY3) | Pharmacokinetics: Maximum Concentration (Cmax) of LY2605541 | 2210 picomoles per liter | Geometric Coefficient of Variation 39 |
Secondary
Glucodynamics: Maximum Glucose Infusion Rate (Rmax)
The maximum observed glucose infusion rate following LY2605541 injection is summarized for each PEG source (LY1, LY2, or LY3).
Time frame: Predose and up to 24 hours post dose in each period
Population: Participants who received at least 1 dose of LY2605541 and had evaluable glucose infusion data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 U/kg LY2605541 (LY1) | Glucodynamics: Maximum Glucose Infusion Rate (Rmax) | 1.21 milligrams per minute per kilogram | Geometric Coefficient of Variation 37 |
| 0.5 U/kg LY2605541 (LY2) | Glucodynamics: Maximum Glucose Infusion Rate (Rmax) | 1.31 milligrams per minute per kilogram | Geometric Coefficient of Variation 57 |
| 0.5 U/kg LY2605541 (LY3) | Glucodynamics: Maximum Glucose Infusion Rate (Rmax) | 1.40 milligrams per minute per kilogram | Geometric Coefficient of Variation 41 |
Secondary
Glucodynamics: Total Amount of Glucose Infused (Gtot)
The total amount of glucose infused following LY2605541 injection is summarized for each PEG source (LY1, LY2, or LY3).
Time frame: Predose and up to 24 hours post dose in each period
Population: Participants who received at least 1 dose of LY2605541 and had evaluable glucose infusion data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 0.5 U/kg LY2605541 (LY1) | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 900 milligrams per kilogram | Geometric Coefficient of Variation 53 |
| 0.5 U/kg LY2605541 (LY2) | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 963 milligrams per kilogram | Geometric Coefficient of Variation 103 |
| 0.5 U/kg LY2605541 (LY3) | Glucodynamics: Total Amount of Glucose Infused (Gtot) | 1190 milligrams per kilogram | Geometric Coefficient of Variation 49 |