Healthy Volunteers
Conditions
Brief summary
This study will include 2 groups (cohorts) of participants: In Cohort A, this study will look at the amount of LY2605541 that is present in the body after it is injected in 3 different locations in the body of the same participant. At least 16 days will pass between each injection. In Cohort B, the study will look at how the body absorbs, distributes, and disposes of LY2605541 in participants aged 65 and over. Participants may enroll in only one cohort.
Interventions
DRUGLY2605541
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Cohort A: are overtly healthy male or female participants, as determined by medical history and physical examination, aged ≥18 to ≤55 years of age * Cohort B: are male or female elderly (≥65 years of age) participants that are overtly healthy, or have stable, chronic medical conditions (including Type 2 Diabetes Mellitus \[T2DM\]) that, in the investigator's opinion, will not significantly alter the disposition of the drug, will not place the participant at increased risk by participating in the study, and will not interfere with interpretation of the data * Male participants agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product * Female participants are women of child-bearing potential who test negative for pregnancy at the time of screening based on a urine pregnancy test and agree to use a reliable method of birth control during the study and for 1 month following the last dose of the investigational product * Female participants are post-menopausal women, or women not of child-bearing potential due to surgical sterilization (at least 3 months after surgical hysterectomy, or at least 3 months after bilateral oophorectomy or bilateral tubal ligation/occlusion with or without hysterectomy) confirmed by medical history, or menopause * Have a body mass index (BMI) of 18.5 to 40 kilogram per meter square (kg/m\^2), inclusive, at time of admission for Period 1 * Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site
Exclusion criteria
* Are participants that intend to start a change in diet or lose weight during the study; participants will be expected to maintain their approximate current weight throughout the study * Are excessive smokers (\>10 cigarettes per day); participants who smoke ≤10 cigarettes per day must be able to stop smoking while residing at the clinical research unit (CRU) Healthy Participants - Cohort A * Have Type 1 Diabetes Mellitus (T1DM), Type 2 Diabetes Mellitus (T2DM), or a fasting blood glucose (BG) \>110 milligrams per deciliter (mg/dL) (6.1 millimoles per liter \[mmol/L\]) with a glycated hemoglobin (HbA1c) of \>6.2% * Intend to use over-the-counter medication within the 7 days or prescription medication within 14 days prior to dosing (apart from contraceptive medication, vitamin/mineral supplements, occasional paracetamol, thyroxine replacement therapy, and hormone replacement therapy). Antihypertensive and lipid lowering agents are permitted, but must have been administered at stable dose(s) for at least 1 month. Elderly Participants - Cohort B * Have T1DM * Are T2DM participants that require insulin treatment, or have a HbA1c of \>10% * Have started new chronic medication(s) or changed the dose of an existing chronic medication \<1 month prior to dosing. Participants are permitted to continue ongoing chronic medications (for example antihypertensive agents, aspirin, non-steroidal anti-inflammatory drugs, lipid lowering agents, thyroxine, hormone replacement therapy, and/or oral anti-diabetic if participants have T2DM). Other stable chronic conditions may be permitted if deemed acceptable by the investigators and Lilly clinical pharmacologist or clinical research physician.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours postdose | AUC from time zero to infinity (AUC(0-∞)) of LY2605541 was evaluated across injection sites (abdominal wall, arm, and thigh). |
| Pharmacokinetics: Observed Maximum Plasma Concentration (Cmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours postdose | Cmax of LY2605541 was evaluated across injection sites (abdominal wall, arm, and thigh). |
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Elderly Participants (≥65 Years of Age) Versus Participants ≤55 Years of Age (Abdominal Injection) | Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours postdose | AUC(0-∞) for LY2605541 was evaluated. |
| Pharmacokinetics: Maximum Plasma Concentration (Cmax): Elderly Participants (≥65 Years of Age) Versus Participants ≤55 Years of Age (Abdominal Injection) | Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours postdose | Cmax of LY2605541 was evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | Predose up to 24 hours post clamp procedure in all treatment periods | Rmax was evaluated across injection sites (abdominal wall, arm, and thigh). |
| Pharmacodynamics: Total Amount of Glucose Infused (Gtot): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | Predose up to 24 hours post clamp procedure in all treatment periods | Gtot was evaluated across injection sites (abdominal wall, arm, and thigh). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2605541: Cohort A (Participants ≤55 Years of Age) Participants ≤55 years of age were randomized to 1 of 6 treatment sequences (ABC, ACB, BAC, BCA, CAB, or CBA), each of which was comprised of the same 3 interventions (A, B, and C). Each intervention was separated by a 16-28 day washout.
Intervention A: participants ≤55 years of age received 1 SC injection of 0.5 U/kg of LY2605541 in the abdominal wall on Day 1 of the treatment period.
Intervention B: participants ≤55 years of age received 1 SC injection of 0.5 U/kg of LY2605541 in the upper arm on Day 1 of the treatment period.
Intervention C: participants ≤55 years of age received 1 SC injection of 0.5 U/kg of LY2605541 in the thigh on Day 1 of the treatment period. | 30 |
| LY2605541: Cohort B (Participants ≥65 Years of Age) Participants ≥65 years of age received 1 SC injection of 0.5 U/kg of LY2605541 in the abdominal wall on Day 1. | 22 |
| Total | 52 |
Baseline characteristics
| Characteristic | LY2605541: Cohort A (Participants ≤55 Years of Age) | Total | LY2605541: Cohort B (Participants ≥65 Years of Age) |
|---|---|---|---|
| Age, Continuous | 37.2 years STANDARD_DEVIATION 9.1 | 51.7 years STANDARD_DEVIATION 18.8 | 71.4 years STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 47 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 23 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 25 Participants | 15 Participants |
| Region of Enrollment United States | 30 Participants | 52 Participants | 22 Participants |
| Sex: Female, Male Female | 10 Participants | 24 Participants | 14 Participants |
| Sex: Female, Male Male | 20 Participants | 28 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 30 | 5 / 30 | 13 / 30 | 7 / 22 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 30 | 0 / 22 |
Outcome results
Primary
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Elderly Participants (≥65 Years of Age) Versus Participants ≤55 Years of Age (Abdominal Injection)
AUC(0-∞) for LY2605541 was evaluated.
Time frame: Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours postdose
Population: Participants in Cohort A and B who received LY2605541 in the abdomen and had evaluable AUC(0-∞) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541: Cohort A (Injection Site: Abdomen) | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Elderly Participants (≥65 Years of Age) Versus Participants ≤55 Years of Age (Abdominal Injection) | 124000 pmol*h/L | Geometric Coefficient of Variation 37 |
| LY2605541: Cohort A (Injection Site: Upper Arm) | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Elderly Participants (≥65 Years of Age) Versus Participants ≤55 Years of Age (Abdominal Injection) | 134000 pmol*h/L | Geometric Coefficient of Variation 30 |
Primary
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A)
AUC from time zero to infinity (AUC(0-∞)) of LY2605541 was evaluated across injection sites (abdominal wall, arm, and thigh).
Time frame: Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours postdose
Population: Participants in Cohort A who received LY2605541 and had evaluable AUC(0-∞) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541: Cohort A (Injection Site: Abdomen) | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 124000 picomoles*hours/liter (pmol*h/L) | Geometric Coefficient of Variation 37 |
| LY2605541: Cohort A (Injection Site: Upper Arm) | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 133000 picomoles*hours/liter (pmol*h/L) | Geometric Coefficient of Variation 39 |
| LY2605541: Cohort A (Injection Site: Thigh) | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 135000 picomoles*hours/liter (pmol*h/L) | Geometric Coefficient of Variation 36 |
Primary
Pharmacokinetics: Maximum Plasma Concentration (Cmax): Elderly Participants (≥65 Years of Age) Versus Participants ≤55 Years of Age (Abdominal Injection)
Cmax of LY2605541 was evaluated.
Time frame: Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours postdose
Population: Participants in Cohort A and B who received LY2605541 in the abdomen and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541: Cohort A (Injection Site: Abdomen) | Pharmacokinetics: Maximum Plasma Concentration (Cmax): Elderly Participants (≥65 Years of Age) Versus Participants ≤55 Years of Age (Abdominal Injection) | 1839.17 pmol/L | Geometric Coefficient of Variation 59 |
| LY2605541: Cohort A (Injection Site: Upper Arm) | Pharmacokinetics: Maximum Plasma Concentration (Cmax): Elderly Participants (≥65 Years of Age) Versus Participants ≤55 Years of Age (Abdominal Injection) | 1829.92 pmol/L | Geometric Coefficient of Variation 49 |
Primary
Pharmacokinetics: Observed Maximum Plasma Concentration (Cmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A)
Cmax of LY2605541 was evaluated across injection sites (abdominal wall, arm, and thigh).
Time frame: Predose and 2, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, and 216 hours postdose
Population: Participants in Cohort A who received LY2605541 and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541: Cohort A (Injection Site: Abdomen) | Pharmacokinetics: Observed Maximum Plasma Concentration (Cmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 1839.17 picomoles/liter (pmol/L) | Geometric Coefficient of Variation 59 |
| LY2605541: Cohort A (Injection Site: Upper Arm) | Pharmacokinetics: Observed Maximum Plasma Concentration (Cmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 1700.68 picomoles/liter (pmol/L) | Geometric Coefficient of Variation 54 |
| LY2605541: Cohort A (Injection Site: Thigh) | Pharmacokinetics: Observed Maximum Plasma Concentration (Cmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 2027.99 picomoles/liter (pmol/L) | Geometric Coefficient of Variation 66 |
Secondary
Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A)
Rmax was evaluated across injection sites (abdominal wall, arm, and thigh).
Time frame: Predose up to 24 hours post clamp procedure in all treatment periods
Population: Participants in Cohort A who received LY2605541 and had evaluable Rmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541: Cohort A (Injection Site: Abdomen) | Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 0.944 milligrams/minute/kilogram (mg/min/kg) | Geometric Coefficient of Variation 88 |
| LY2605541: Cohort A (Injection Site: Upper Arm) | Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 0.935 milligrams/minute/kilogram (mg/min/kg) | Geometric Coefficient of Variation 83 |
| LY2605541: Cohort A (Injection Site: Thigh) | Pharmacodynamics: Maximum Glucose Infusion Rate (Rmax): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 0.738 milligrams/minute/kilogram (mg/min/kg) | Geometric Coefficient of Variation 144 |
Secondary
Pharmacodynamics: Total Amount of Glucose Infused (Gtot): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A)
Gtot was evaluated across injection sites (abdominal wall, arm, and thigh).
Time frame: Predose up to 24 hours post clamp procedure in all treatment periods
Population: Participants in Cohort A who received LY2605541 and had evaluable Gtot data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2605541: Cohort A (Injection Site: Abdomen) | Pharmacodynamics: Total Amount of Glucose Infused (Gtot): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 674 milligrams/kilograms (mg/kg) | Geometric Coefficient of Variation 109 |
| LY2605541: Cohort A (Injection Site: Upper Arm) | Pharmacodynamics: Total Amount of Glucose Infused (Gtot): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 633 milligrams/kilograms (mg/kg) | Geometric Coefficient of Variation 102 |
| LY2605541: Cohort A (Injection Site: Thigh) | Pharmacodynamics: Total Amount of Glucose Infused (Gtot): Injection Site (Arm and Thigh) Versus Abdominal Wall Injection (Cohort A) | 454 milligrams/kilograms (mg/kg) | Geometric Coefficient of Variation 204 |