Healthy Volunteers
Conditions
Keywords
Diabetes Mellitus, Type 2
Brief summary
The purpose of this study is to compare 2 formulations of the study drug (LY2608204) in terms of how much gets into the blood stream and how long it takes the body to get rid of it. Information about any side effects that may occur will also be collected.
Interventions
DRUGLY2608204 Reference
Administered orally
DRUGLY2608204 Test
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be a healthy male or a female who cannot become pregnant * Must have body mass index (BMI) of 18.5 to 32 kg/m², inclusive * Blood pressure as well as blood and urine laboratory test results must be acceptable for the study * The veins must be suitable for easy blood collection * Must be willing to be available for the whole study and be willing to follow study procedures * Must have given written informed consent
Exclusion criteria
* Were in another new drug or medical research study in the last 30 days * Have participated in this study or any other study with LY2608204 before * Have taken drugs similar to LY2608204 (glucokinase activators) before and was found to be allergic to the drug * Have drug allergy to more than 3 types of medications given by injection * Currently have or used to have health problems or laboratory test results that in the opinion of the doctor, could interfere with understanding the results of this study * Electrocardiogram (ECG) readings are not suitable for the study * Are infected with hepatitis B * Are infected with human immunodeficiency disease virus (HIV) * Are using or intend to use over-the-counter medication or prescription medications within 14 days, from the start of the first study dosing until end of study * Are unwilling to follow dietary restrictions/requirements for the study including (i) refrain from consuming foods or beverages containing grapefruit pomelo, star fruit, or Seville orange within 14 days of the start of the study drug dosing until collection of the last blood sample for drug assay; (ii) consume only the meals provided during dosing day at the clinical research unit (CRU) * Have a regular alcohol intake greater than 21 units per week (males) and 14 units per week (females) or are not willing to abstain from alcohol while in the research unit * Smoke more than 10 cigarettes per day or are not willing to abstain from smoking while at the clinic * Have a history of drug or alcohol abuse * Have donated 450 milliliter (mL) or more of blood in the last 3 months (this is about the same as the usual volume given in a blood donation) * The study doctor thinks the subject should not participate for any other reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | Predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 and 168 hours | Area under the concentration versus time curve from zero to infinity \[AUC(0-∞)\] was calculated from the data. The values for AUC were log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence and period, and a random factor for subject. |
| Maximum Observed Drug Concentration (Cmax) | Predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 and 168 hours | Maximum observed drug concentration (Cmax) was observed from the data. The values for Cmax were log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence and period, and a random factor for subject. |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants A single oral dose of 80 mg LY2608204 reference formulation in Period 1 and a single oral dose of 80 mg LY2608204 test formulation in Period 2; or a single oral dose of 80 mg test formulation in Period 1 and a single oral dose of 80 mg reference formulation in Period 2. There is a washout period of at least 14 days between dosing periods. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 34.3 years STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized Asian | 14 Participants |
| Race/Ethnicity, Customized White | 2 Participants |
| Region of Enrollment Singapore | 16 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 16 | 10 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 |
Outcome results
Primary
Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞])
Area under the concentration versus time curve from zero to infinity \[AUC(0-∞)\] was calculated from the data. The values for AUC were log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence and period, and a random factor for subject.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 and 168 hours
Population: All randomized participants who took at least one dose of study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2608204 Free Base (Reference Formulation) | Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 974 nanogram.hour per milliliter (ng.h/mL) | Geometric Coefficient of Variation 39 |
| LY2608204 Hydrochloride (HCl) Salt (Test Formulation) | Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) | 1080 nanogram.hour per milliliter (ng.h/mL) | Geometric Coefficient of Variation 35 |
90% CI: [1, 1.16]Mixed Models Analysis
Primary
Maximum Observed Drug Concentration (Cmax)
Maximum observed drug concentration (Cmax) was observed from the data. The values for Cmax were log-transformed and analyzed using a linear mixed effects model with fixed factor for formulation, sequence and period, and a random factor for subject.
Time frame: Predose, 1, 2, 4, 6, 8, 12, 16, 24, 48, 72, 96, 120, 144 and 168 hours
Population: All randomized participants who took at least one dose of study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2608204 Free Base (Reference Formulation) | Maximum Observed Drug Concentration (Cmax) | 24.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| LY2608204 Hydrochloride (HCl) Salt (Test Formulation) | Maximum Observed Drug Concentration (Cmax) | 30.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
90% CI: [1.07, 1.31]Mixed Models Analysis