Diabetes Mellitus, Type 2
Conditions
Brief summary
This will be the first study in which LY2881835 is given to humans in order to evaluate the safety and any side effects of LY2881835 in humans as well as how long LY2881835 stays in the body and its effect on blood sugar levels. The study consists of two parts. In part A, healthy subjects will participate and in part B, patients with type 2 Diabetes Mellitus (T2DM) will participate.
Interventions
DRUGLY2881835
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
All subjects: * Are a healthy male or a healthy female who cannot become pregnant, or are patients with Type 2 Diabetes Mellitus (T2DM) who are not taking any drugs to lower blood sugar except metformin * Have a body mass index (BMI) of at least 18.5 kilograms per meter squared (kg/m²) at screening * Have blood pressure, pulse rate and clinical laboratory tests within the normal range for the population or investigator site, or with abnormalities deemed clinical insignificant by the investigator * Have veins that are suitable for easy blood collection * Are reliable and willing to be available for the whole study and are willing to follow study procedures * Must have given written informed consent Subjects with Type 2 Diabetes Mellitus (T2DM) only: * Do not have any change to their diabetes treatment for at least 4 weeks prior to screening * Have a glycosylated hemoglobin (HbA1c) level greater than or equal to 6% and less than or equal to 11% at screening
Exclusion criteria
All subjects: * Are currently participating in or were in another new drug or medical research study in the last 30 days * Have participated in this study before * Have known allergies to compounds related to the study drug * 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 * Intend to use over-the-counter or prescription medications within 14 days prior to dosing or during the study. Hormone replacement therapy and intermittent use of paracetamol during the study is acceptable. For patients with Type 2 Diabetes Mellitus, medicines for control of high fats (For example, cholesterol), high blood pressure, are allowed. * Have electrocardiogram (ECG) readings that are not suitable for the study * Are unwilling to follow dietary restrictions/requirements for the study including 1) 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 and 2) consume only the meals provided during inpatient stays at the clinical research unit * Have a history of drug or alcohol abuse * Are infected with hepatitis B * Are infected with human immunodeficiency disease virus (HIV) * Have donated 450 milliliters (mL) or more of blood in the last 3 months or provided any blood donation within the last month from screening * 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 * The study doctor thinks the subject should not participate for any other reasons Subjects with Type 2 Diabetes Mellitus (T2DM) only: * Have health complications due to poorly controlled diabetes as shown by blood and urine laboratory test results or based on physical examination and medical assessment, as determined by the study doctor * Were hospitalised for poor control of their diabetes (ketoacidotic episode) in the last 6 months * Currently using or have used insulin in the last 1 year to control their diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Adverse Effects | Baseline to study completion up to 3 months | Clinically significant adverse effects are treatment emergent adverse events (TEAEs) possibly related to study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose | Not all the participants had quantifiable plasma concentrations at 48 hours, therefore only Cmax up to 24 hours post-dose is provided. |
| Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose | Not all the participants had quantifiable plasma concentrations at 48 hours, therefore only Tmax up to 24 hours post dose is provided. |
| Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24hours (h) post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose | Not all the participants had quantifiable plasma concentrations at 48 hours, therefore only AUC from time zero to 24 hours \[AUC(0-24 hours)\] is provided. |
| Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC) | Part A: Predose, 1.5 and 2.5 h post-dose; Part B: Predose, 1.5 and 2.5 h post-dose | Glucagon-like peptide (active GLP-1) area under the serum concentration versus time curve (AUEC) was calculated using the linear trapezoidal rule from time 0 to 2.5 hours. |
| C-Peptide Area Under the Effective Concentration Curve (AUEC) | Part A: Predose, 1.0, 1.5, 2.5, 4, 5, 6 and 24 h post-dose; Part B: Predose, 1.0, 1.5, 2.5, 4, 5, 6 and 24 h post-dose | C-Peptide area under the serum concentration versus time curve (AUEC) was calculated using the linear trapezoidal rule from time 0 to 6 hours. |
| Glucose Area Under the Effective Concentration Curve (AUEC) | Part A: Predose, 1.0, 1.5, 2.5, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18 and 24 h post-dose; Part B: Predose, 1.0, 1.5, 2.5, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18 and 24 h post-dose | Glucose area under the serum concentration versus time curve (AUEC) was calculated using the linear trapezoidal rule from time 0 to 24 hours. |
Countries
Singapore
Participant flow
Pre-assignment details
This is a 2-part (Part A and Part B) crossover study with four periods.In Part A, 8 participants were dosed at each dose level in 4 study periods (1 additional participant was dosed only in 1 study period). In Part B, a single cohort of 9 participants with type 2 diabetes mellitus (T2DM) participated in 3 dosing periods.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Part A (Healthy): Sequence 1 Participants received single oral doses of 0.5 milligram (mg), 1.5 mg, 4.5 mg LY2881835 and placebo capsules on day 1 of each treatment period as per the below dosing sequence.
Period 1: 0.5 mg LY2881835, Period 2: 1.5 mg LY2881835, Period 3: 4.5 mg LY2881835, Period 4: Placebo. | 2 |
| Cohort 1: Part A (Healthy): Sequence 2 Participants received single oral doses of 0.5 mg, 1.5 mg, 8.4 mg LY2881835 and placebo capsules on day 1 of each treatment period as per the below dosing sequence.
Period 1: 0.5 mg LY2881835, Period 2: 1.5 mg LY2881835, Period 3: Placebo, Period 4: 8.4 mg LY2881835. | 2 |
| Cohort 1: Part A (Healthy): Sequence 3 Participants received single oral doses of 0.5 mg, 4.5 mg, 8.4 mg LY2881835 and placebo capsules on day 1 of each treatment period as per the below dosing sequence.
Period 1: 0.5 mg LY2881835, Period 2: Placebo, Period 3: 4.5 mg LY2881835, Period 4: 8.4 mg LY2881835. | 2 |
| Cohort 1: Part A (Healthy): Sequence 4 Participants received single oral doses of 1.5 mg, 4.5 mg, 8.4 mg LY2881835 and placebo capsules on day 1 of each treatment period as per the below dosing sequence.
Period 1: Placebo, Period 2: 1.5 mg LY2881835, Period 3: 4.5 mg LY2881835, Period 4: 8.4 mg LY2881835. | 3 |
| Cohort 2: Part B (T2DM): Sequence 1 Participants received single oral doses of 8.4 mg LY2881835 and placebo capsules on day 1 of each treatment period as per the below dosing sequence.
Period 1: 8.4 mg LY2881835, Period 2: 8.4 mg LY2881835, Period 3: Placebo. | 3 |
| Cohort 2: Part B (T2DM): Sequence 2 Participants received single oral doses of 8.4 mg LY2881835 and placebo capsules on day 1 of each treatment period as per the below dosing sequence.
Period 1: 8.4 mg LY2881835, Period 2: Placebo, Period 3: 8.4 mg LY2881835. | 3 |
| Cohort 2: Part B (T2DM): Sequence 3 Participants received single oral doses of 8.4 mg LY2881835 and placebo capsules on day 1 of each treatment period as per the below dosing sequence.
Period 1: Placebo, Period 2: 8.4 mg LY2881835, Period 3: 8.4 mg LY2881835. | 3 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1: Part A (Healthy): Sequence 2 | Cohort 1: Part A (Healthy): Sequence 3 | Cohort 1: Part A (Healthy): Sequence 4 | Cohort 2: Part B (T2DM): Sequence 1 | Cohort 1: Part A (Healthy): Sequence 1 | Cohort 2: Part B (T2DM): Sequence 2 | Cohort 2: Part B (T2DM): Sequence 3 |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 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 |
| Age, Categorical Between 18 and 65 years | 18 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 18 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 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 |
| 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 |
| Race (NIH/OMB) Unknown or Not Reported | 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 |
| Region of Enrollment Singapore | 18 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 8 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 10 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 0 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 3 / 9 | 3 / 6 | 3 / 6 | 2 / 6 | 4 / 6 | 3 / 9 | 4 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Number of Participants With Clinically Significant Adverse Effects
Clinically significant adverse effects are treatment emergent adverse events (TEAEs) possibly related to study drug.
Time frame: Baseline to study completion up to 3 months
Population: All enrolled participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Placebo | Number of Participants With Clinically Significant Adverse Effects | 0 participants |
| Part A - 0.5 mg LY2881835 | Number of Participants With Clinically Significant Adverse Effects | 0 participants |
| Part A - 1.5 mg LY2881835 | Number of Participants With Clinically Significant Adverse Effects | 1 participants |
| Part A - 4.5 mg LY2881835 | Number of Participants With Clinically Significant Adverse Effects | 0 participants |
| Part A - 8.4 mg LY2881835 | Number of Participants With Clinically Significant Adverse Effects | 0 participants |
| Part B - Placebo | Number of Participants With Clinically Significant Adverse Effects | 1 participants |
| Part B - 8.4 mg LY2881835 | Number of Participants With Clinically Significant Adverse Effects | 2 participants |
Secondary
C-Peptide Area Under the Effective Concentration Curve (AUEC)
C-Peptide area under the serum concentration versus time curve (AUEC) was calculated using the linear trapezoidal rule from time 0 to 6 hours.
Time frame: Part A: Predose, 1.0, 1.5, 2.5, 4, 5, 6 and 24 h post-dose; Part B: Predose, 1.0, 1.5, 2.5, 4, 5, 6 and 24 h post-dose
Population: All participants who received study drug and had evaluable C-Peptide data. Each participant in group Part B, Study Periods (SP) 1, 2, 3-8.4 mg LY2881835 was dosed and had corresponding C-Peptide measures in 2 of the 3 SP in Part B resulting in 18 samples being analyzed. Analysis used data according to the treatment participants actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo | C-Peptide Area Under the Effective Concentration Curve (AUEC) | 5852.8 picomoles*hour/liter (pmol*h/L) | Standard Deviation 1266.7 |
| Part A - 0.5 mg LY2881835 | C-Peptide Area Under the Effective Concentration Curve (AUEC) | 6313.7 picomoles*hour/liter (pmol*h/L) | Standard Deviation 1870.3 |
| Part A - 1.5 mg LY2881835 | C-Peptide Area Under the Effective Concentration Curve (AUEC) | 7069.5 picomoles*hour/liter (pmol*h/L) | Standard Deviation 2065.3 |
| Part A - 4.5 mg LY2881835 | C-Peptide Area Under the Effective Concentration Curve (AUEC) | 4962.2 picomoles*hour/liter (pmol*h/L) | Standard Deviation 1192.2 |
| Part A - 8.4 mg LY2881835 | C-Peptide Area Under the Effective Concentration Curve (AUEC) | 7421.5 picomoles*hour/liter (pmol*h/L) | Standard Deviation 3047.4 |
| Part B - Placebo | C-Peptide Area Under the Effective Concentration Curve (AUEC) | 6145.6 picomoles*hour/liter (pmol*h/L) | Standard Deviation 2192.4 |
| Part B - 8.4 mg LY2881835 | C-Peptide Area Under the Effective Concentration Curve (AUEC) | 6477.8 picomoles*hour/liter (pmol*h/L) | Standard Deviation 2113.4 |
Secondary
Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC)
Glucagon-like peptide (active GLP-1) area under the serum concentration versus time curve (AUEC) was calculated using the linear trapezoidal rule from time 0 to 2.5 hours.
Time frame: Part A: Predose, 1.5 and 2.5 h post-dose; Part B: Predose, 1.5 and 2.5 h post-dose
Population: All participants who received study drug and had evaluable GLP-1 data. Each participant in group Part B, Study Periods (SP) 1, 2 and 3-8.4 mg LY2881835 was dosed and had corresponding GLP-1 measures in 2 of the 3 SP in Part B resulting in 18 samples being analyzed. Analysis used data according to the treatment participants actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo | Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC) | 3.029 picomoles*hour/liter (pmol*h/L) | Standard Deviation 1.097 |
| Part A - 0.5 mg LY2881835 | Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC) | 3.277 picomoles*hour/liter (pmol*h/L) | Standard Deviation 1.032 |
| Part A - 1.5 mg LY2881835 | Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC) | 2.838 picomoles*hour/liter (pmol*h/L) | Standard Deviation 0.759 |
| Part A - 4.5 mg LY2881835 | Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC) | 3.113 picomoles*hour/liter (pmol*h/L) | Standard Deviation 1.389 |
| Part A - 8.4 mg LY2881835 | Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC) | 3.362 picomoles*hour/liter (pmol*h/L) | Standard Deviation 0.938 |
| Part B - Placebo | Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC) | 4.249 picomoles*hour/liter (pmol*h/L) | Standard Deviation 2.14 |
| Part B - 8.4 mg LY2881835 | Glucagon-Like Peptide (Active GLP-1) Area Under the Effective Concentration Curve (AUEC) | 5.268 picomoles*hour/liter (pmol*h/L) | Standard Deviation 2.266 |
Secondary
Glucose Area Under the Effective Concentration Curve (AUEC)
Glucose area under the serum concentration versus time curve (AUEC) was calculated using the linear trapezoidal rule from time 0 to 24 hours.
Time frame: Part A: Predose, 1.0, 1.5, 2.5, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18 and 24 h post-dose; Part B: Predose, 1.0, 1.5, 2.5, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18 and 24 h post-dose
Population: All participants who received study drug and had evaluable glucose data. Each participant in group Part B, Study Periods (SP) 1, 2 and 3-8.4 mg LY2881835 was dosed and had corresponding glucose measures in 2 of the 3 SP in Part B resulting in 18 samples being analyzed. Analysis used data according to the treatment participants actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo | Glucose Area Under the Effective Concentration Curve (AUEC) | 2282 milligrams*hour/deciliter (mg*hr/dL) | Standard Deviation 291 |
| Part A - 0.5 mg LY2881835 | Glucose Area Under the Effective Concentration Curve (AUEC) | 2448 milligrams*hour/deciliter (mg*hr/dL) | Standard Deviation 183 |
| Part A - 1.5 mg LY2881835 | Glucose Area Under the Effective Concentration Curve (AUEC) | 2089 milligrams*hour/deciliter (mg*hr/dL) | Standard Deviation 146 |
| Part A - 4.5 mg LY2881835 | Glucose Area Under the Effective Concentration Curve (AUEC) | 2354 milligrams*hour/deciliter (mg*hr/dL) | Standard Deviation 72 |
| Part A - 8.4 mg LY2881835 | Glucose Area Under the Effective Concentration Curve (AUEC) | 2159 milligrams*hour/deciliter (mg*hr/dL) | Standard Deviation 133 |
| Part B - Placebo | Glucose Area Under the Effective Concentration Curve (AUEC) | 3640 milligrams*hour/deciliter (mg*hr/dL) | Standard Deviation 711 |
| Part B - 8.4 mg LY2881835 | Glucose Area Under the Effective Concentration Curve (AUEC) | 3769 milligrams*hour/deciliter (mg*hr/dL) | Standard Deviation 719 |
Secondary
Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835
Not all the participants had quantifiable plasma concentrations at 48 hours, therefore only AUC from time zero to 24 hours \[AUC(0-24 hours)\] is provided.
Time frame: Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24hours (h) post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose
Population: All participants who received study drug and had evaluable PK data. Each participant in group Part B, Study Periods 1, 2 and 3 - 8.4 mg LY2881835 was dosed and had corresponding PK measures in 2 of the 3 study periods in Part B resulting in 18 samples being analyzed. Analysis used data according to the treatment the participants actually received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo | Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | 54.8 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 39 |
| Part A - 0.5 mg LY2881835 | Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | 125 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 47 |
| Part A - 1.5 mg LY2881835 | Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | 340 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| Part A - 4.5 mg LY2881835 | Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | 767 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 48 |
| Part A - 8.4 mg LY2881835 | Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | 820 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 20 |
| Part B - Placebo | Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | 683 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| Part B - 8.4 mg LY2881835 | Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | 658 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| Part B, Study Periods 1, 2, and 3 - 8.4 mg LY2881835 | Pharmacokinetics (PK): Area Under the Curve (AUC) of LY2881835 | 717 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835
Not all the participants had quantifiable plasma concentrations at 48 hours, therefore only Cmax up to 24 hours post-dose is provided.
Time frame: Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose
Population: All participants who received study drug and had evaluable PK data. Each participant in group Part B, Study Periods 1, 2 and 3 - 8.4 mg LY2881835 was dosed and had corresponding PK measures in 2 of the 3 study periods in Part B resulting in 18 samples being analyzed. Analysis used data according to the treatment the participants actually received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo | Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | 7.44 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 16 |
| Part A - 0.5 mg LY2881835 | Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | 14.7 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| Part A - 1.5 mg LY2881835 | Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | 47.1 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Part A - 4.5 mg LY2881835 | Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | 89.9 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 42 |
| Part A - 8.4 mg LY2881835 | Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | 93.0 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 30 |
| Part B - Placebo | Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | 85.1 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| Part B - 8.4 mg LY2881835 | Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | 77.8 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| Part B, Study Periods 1, 2, and 3 - 8.4 mg LY2881835 | Pharmacokinetics (PK): Maximum Concentration (Cmax) Of LY2881835 | 85.1 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
Secondary
Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835
Not all the participants had quantifiable plasma concentrations at 48 hours, therefore only Tmax up to 24 hours post dose is provided.
Time frame: Part A: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose; Part B: Predose, 0.5, 1.5, 2.5, 4, 6, 12, 18 and 24 h post-dose
Population: All participants who received study drug and had evaluable PK data. Each participant in group Part B, Study Periods 1, 2 and 3 - 8.4 mg LY2881835 was dosed and had corresponding PK measures in 2 of the 3 study periods in Part B resulting in 18 samples being analyzed. Analysis used data according to the treatment the participants actually received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A - Placebo | Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | 2.50 hours |
| Part A - 0.5 mg LY2881835 | Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | 2.50 hours |
| Part A - 1.5 mg LY2881835 | Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | 3.25 hours |
| Part A - 4.5 mg LY2881835 | Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | 2.50 hours |
| Part A - 8.4 mg LY2881835 | Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | 4.25 hours |
| Part B - Placebo | Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | 3.25 hours |
| Part B - 8.4 mg LY2881835 | Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | 4.25 hours |
| Part B, Study Periods 1, 2, and 3 - 8.4 mg LY2881835 | Pharmacokinetics (PK): Time to Maximum Concentration (Tmax) of LY2881835 | 3.25 hours |