Diabetes Mellitus, Type 2
Conditions
Brief summary
The aim of this trial is to evaluate the safety of the study drug in healthy participants and participants with diabetes. It will investigate how much of the study drug 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. The study consists of two parts. Part A will study healthy participants in up to 3 dosing periods over approximately 6 weeks. Part B will study participants with diabetes in up to 3 dosing periods over approximately 6 weeks.
Interventions
DRUGPlacebo
Administered orally as capsules
DRUGLY2922083
Administered orally as capsules
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
No
Inclusion criteria
For all participants : * Must be a male, or a female who cannot become pregnant, and who is either a healthy participant, or who has type 2 diabetes * Have a screening body mass index (BMI) of at least 18.0 kilograms per square meter (kg/m\^2) * Have blood pressure, pulse rate, blood and urine laboratory test results acceptable for the study For participants with T2DM: * Do not have any change to their diabetes treatment (exercise with or without metformin) for at least 4 weeks prior to screening * Have a glycated hemoglobin (HbA1c) value of greater than or equal to 6% and less than or equal to 11% at screening
Exclusion criteria
For all participants : * Are currently participating in another clinical study or completed one in the last 30 days * Are allergic to LY2922083 or other related drugs * Have a history of significant heart, lung, liver, kidney, stomach or brain disease, or have any medical problems which may cause an increased risk during the study * Have electrocardiogram (ECG) readings that are not suitable for the study * Have a history of hepatitis or jaundice * Are infected with hepatitis B * Are infected with hepatitis C * Are infected with human immunodeficiency virus (HIV) * Have donated more than 450 milliliters (mL) of blood in the last 3 months or have donated any blood in the last month * Have a regular alcohol intake greater than 21 units/week (male), or 14 units/week (female), or are unwilling to stop alcohol as required by the study restrictions (1 unit = 360 mL of beer, or 150 mL of wine, or 45 mL of spirits) * Smoke more than 10 cigarettes per day or are not willing to abstain from smoking while at the clinic For participants with T2DM : * Have had heart disease or stroke within 6 months before entering the study * 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 * Have been hospitalized for poor control of diabetes (keto-acidotic episode) in the last 6 months * Have used insulin to control diabetes in the last 1 year * Show symptoms of high blood sugar (for example, frequent urination, always feeling thirsty, or unexpected weight loss)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | Baseline through study completion (up to 70 days) | Events deemed by the Investigator to be SAEs related to study drug administration are reported. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | Predose up to 72 hours (h) after each dose of study drug (Part A: predose, 0.5, 1.5, 2.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose. Part B: predose, 0.5, 1.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose.) | — |
| PK: Maximum Concentration (Cmax) of LY2922083 | Predose up to 72 h after each dose of study drug (Part A: predose, 0.5, 1.5, 2.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose. Part B: predose, 0.5, 1.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose.) | — |
| Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | Baseline (predose for Part A and Day -1 time-matched for Part B), up to 24 h postdose (1.5, 2.5, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, and 24 h postdose) | Least Squares (LS) mean values were adjusted for baseline, treatment, period, treatment sequence, participant and error. |
| Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | Baseline (predose for Part A and Day -1 time-matched for Part B), up to 6 h postdose (1.5, 2.5, 4, 4.5, 5, and 6 h postdose) | LS mean values were adjusted for baseline, treatment, period, treatment sequence, participant and error. |
Countries
Singapore
Participant flow
Pre-assignment details
Single ascending dose crossover study with 2 parts and 3 periods per part. Part A had 3 cohorts (healthy participants). Part B had 1 cohort \[with type 2 diabetes mellitus (T2DM)\]. Participants in Part A, Cohort 3 completed 2 periods, as ninth (contingency) dose not tested based on interim data. There was ≥10 days between dosing for any participant.
Participants by arm
| Arm | Count |
|---|---|
| Part A, Cohort 1, Sequence 1 Healthy participants received a single oral dose of the following:
Period 1: Placebo Period 2: 1.5 milligrams (mg) LY2922083 Period 3: 5 mg LY2922083 | 3 |
| Part A, Cohort 1, Sequence 2 Healthy participants received a single oral dose of the following:
Period 1: 0.5 mg LY2922083 Period 2: Placebo Period 3: 5 mg LY2922083 | 3 |
| Part A, Cohort 1, Sequence 3 Healthy participants received a single oral dose of the following:
Period 1: 0.5 mg LY2922083 Period 2: 1.5 mg LY2922083 Period 3: Placebo | 3 |
| Part A, Cohort 2, Sequence 1 Healthy participants received a single oral dose of the following:
Period 1: Placebo Period 2: 50 mg LY2922083 Period 3: 150 mg LY2922083 | 3 |
| Part A, Cohort 2, Sequence 2 Healthy participants received a single oral dose of the following:
Period 1: 15 mg LY2922083 Period 2: Placebo Period 3: 150 mg LY2922083 | 3 |
| Part A, Cohort 2, Sequence 3 Healthy participants received a single oral dose of the following:
Period 1: 15 mg LY2922083 Period 2: 50 mg LY2922083 Period 3: Placebo | 3 |
| Part A, Cohort 3, Sequence 1 Healthy participants received a single oral dose of the following:
Period 1: Placebo Period 2: 845 mg LY2922083 | 3 |
| Part A, Cohort 3, Sequence 2 Healthy participants received a single oral dose of the following:
Period 1: 450 mg LY2922083 Period 2: Placebo | 3 |
| Part A, Cohort 3, Sequence 3 Healthy participants received a single oral dose of the following:
Period 1: 450 mg LY2922083 Period 2: 845 mg LY2922083 | 3 |
| Part B, Cohort 1, Sequence 1 Participants with T2DM received a single oral dose of the following:
Period 1: Placebo Period 2: 450 mg LY2922083 Period 3: 845 mg LY2922083 | 3 |
| Part B, Cohort 1, Sequence 2 Participants with T2DM received a single oral dose of the following:
Period 1: 150 mg LY2922083 Period 2: Placebo Period 3: 845 mg LY2922083 | 3 |
| Part B, Cohort 1, Sequence 3 Participants with T2DM received a single oral dose of the following:
Period 1: 150 mg LY2922083 Period 2: 450 mg LY2922083 Period 3: Placebo | 3 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Intervention Period 2 and Washout | Contingency dose not tested | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 3 | 0 | 0 | 0 |
| Intervention Period 2 and Washout | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A, Cohort 1, Sequence 2 | Part A, Cohort 1, Sequence 3 | Part A, Cohort 2, Sequence 1 | Part A, Cohort 2, Sequence 2 | Part A, Cohort 2, Sequence 3 | Part A, Cohort 1, Sequence 1 | Part A, Cohort 3, Sequence 1 | Part A, Cohort 3, Sequence 2 | Part A, Cohort 3, Sequence 3 | Part B, Cohort 1, Sequence 1 | Part B, Cohort 1, Sequence 2 | Part B, Cohort 1, Sequence 3 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 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 | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 35 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 3 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 | 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 | 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 | 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Singapore | 36 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 34 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 3 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 | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 32 | 1 / 6 | 2 / 6 | 0 / 6 | 2 / 6 | 5 / 6 | 9 / 12 | 8 / 12 | 6 / 12 |
| serious Total, serious adverse events | 0 / 32 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Number of Participants With 1 or More Serious Adverse Event(s) (SAEs)
Events deemed by the Investigator to be SAEs related to study drug administration are reported. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline through study completion (up to 70 days)
Population: Safety population: all participants who received at least 1 dose of study drug or placebo, and had at least 1 postdose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo (Parts A and B) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| 0.5 mg LY2922083 (Part A) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| 1.5 mg LY2922083 (Part A) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| 5 mg LY2922083 (Part A) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| 15 mg LY2922083 (Part A) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| 50 mg LY2922083 (Part A) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| 150 mg LY2922083 (Parts A and B) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| 450 mg LY2922083 (Parts A and B) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
| 845 mg LY2922083 (Parts A and B) | Number of Participants With 1 or More Serious Adverse Event(s) (SAEs) | 0 Participants |
Secondary
Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)]
Least Squares (LS) mean values were adjusted for baseline, treatment, period, treatment sequence, participant and error.
Time frame: Baseline (predose for Part A and Day -1 time-matched for Part B), up to 24 h postdose (1.5, 2.5, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, and 24 h postdose)
Population: All participants who received at least 1 dose of the study drug or placebo and had sufficient pharmacodynamic data to calculate glucose AUEC(0-24).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts A and B) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 7.08 millimoles*hour per liter (mmol*h/L) | Standard Error 1.17 |
| 0.5 mg LY2922083 (Part A) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 6.32 millimoles*hour per liter (mmol*h/L) | Standard Error 2.86 |
| 1.5 mg LY2922083 (Part A) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | -0.02 millimoles*hour per liter (mmol*h/L) | Standard Error 2.84 |
| 5 mg LY2922083 (Part A) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 12.34 millimoles*hour per liter (mmol*h/L) | Standard Error 2.78 |
| 15 mg LY2922083 (Part A) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 8.88 millimoles*hour per liter (mmol*h/L) | Standard Error 3 |
| 50 mg LY2922083 (Part A) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 8.40 millimoles*hour per liter (mmol*h/L) | Standard Error 2.94 |
| 150 mg LY2922083 (Parts A and B) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 4.78 millimoles*hour per liter (mmol*h/L) | Standard Error 2.73 |
| 450 mg LY2922083 (Parts A and B) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 6.13 millimoles*hour per liter (mmol*h/L) | Standard Error 2.87 |
| 845 mg LY2922083 (Parts A and B) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 3.68 millimoles*hour per liter (mmol*h/L) | Standard Error 2.87 |
| 450 mg LY2922083 (Part B) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 4.60 millimoles*hour per liter (mmol*h/L) | Standard Error 1.9 |
| 845 mg LY2922083 (Part B) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 8.48 millimoles*hour per liter (mmol*h/L) | Standard Error 3.56 |
| 450 mg LY2922083 (Part B) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 1.18 millimoles*hour per liter (mmol*h/L) | Standard Error 3.18 |
| 845 mg LY2922083 (Part B) | Change From Baseline in Blood Glucose Area Under the Effective Concentration Curve From Time 0 to 24 h Postdose [AUEC(0-24)] | 3.05 millimoles*hour per liter (mmol*h/L) | Standard Error 3.24 |
Secondary
Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)]
LS mean values were adjusted for baseline, treatment, period, treatment sequence, participant and error.
Time frame: Baseline (predose for Part A and Day -1 time-matched for Part B), up to 6 h postdose (1.5, 2.5, 4, 4.5, 5, and 6 h postdose)
Population: All participants who received at least 1 dose of the study drug or placebo and had sufficient pharmacodynamic data to calculate C-peptide AUEC(0-6).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts A and B) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 6638.85 picomoles*hour per liter (pmol*h/L) | Standard Error 557.21 |
| 0.5 mg LY2922083 (Part A) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 6518.87 picomoles*hour per liter (pmol*h/L) | Standard Error 1195.43 |
| 1.5 mg LY2922083 (Part A) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 8107.68 picomoles*hour per liter (pmol*h/L) | Standard Error 1194.99 |
| 5 mg LY2922083 (Part A) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 5742.81 picomoles*hour per liter (pmol*h/L) | Standard Error 1172.87 |
| 15 mg LY2922083 (Part A) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 8283.17 picomoles*hour per liter (pmol*h/L) | Standard Error 1225.04 |
| 50 mg LY2922083 (Part A) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 6715.88 picomoles*hour per liter (pmol*h/L) | Standard Error 1221.1 |
| 150 mg LY2922083 (Parts A and B) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 5653.51 picomoles*hour per liter (pmol*h/L) | Standard Error 1140.26 |
| 450 mg LY2922083 (Parts A and B) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 4525.49 picomoles*hour per liter (pmol*h/L) | Standard Error 1204.61 |
| 845 mg LY2922083 (Parts A and B) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 5554.47 picomoles*hour per liter (pmol*h/L) | Standard Error 1203.47 |
| 450 mg LY2922083 (Part B) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 1670.60 picomoles*hour per liter (pmol*h/L) | Standard Error 580.54 |
| 845 mg LY2922083 (Part B) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 2865.28 picomoles*hour per liter (pmol*h/L) | Standard Error 1174.05 |
| 450 mg LY2922083 (Part B) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 1061.59 picomoles*hour per liter (pmol*h/L) | Standard Error 1178.54 |
| 845 mg LY2922083 (Part B) | Change From Baseline in C-Peptide Area Under the Effective Concentration Curve From Time 0 to 6 h Postdose [AUEC(0-6)] | 512.14 picomoles*hour per liter (pmol*h/L) | Standard Error 1180.77 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083
Time frame: Predose up to 72 hours (h) after each dose of study drug (Part A: predose, 0.5, 1.5, 2.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose. Part B: predose, 0.5, 1.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose.)
Population: All participants who received at least 1 dose of the study drug and had sufficient PK data to calculate AUC(0-∞).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts A and B) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 25.9 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| 0.5 mg LY2922083 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 79.5 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 47 |
| 1.5 mg LY2922083 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 220 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 52 |
| 5 mg LY2922083 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 612 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| 15 mg LY2922083 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 1560 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| 50 mg LY2922083 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 3270 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 34 |
| 150 mg LY2922083 (Parts A and B) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 10200 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| 450 mg LY2922083 (Parts A and B) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 16900 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 42 |
| 845 mg LY2922083 (Parts A and B) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 4900 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 117 |
| 450 mg LY2922083 (Part B) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 10400 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 60 |
| 845 mg LY2922083 (Part B) | Pharmacokinetics (PK): Area Under the Concentration Curve From Time 0 to Infinite Time [AUC(0-∞)] of LY2922083 | 24400 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 89 |
Secondary
PK: Maximum Concentration (Cmax) of LY2922083
Time frame: Predose up to 72 h after each dose of study drug (Part A: predose, 0.5, 1.5, 2.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose. Part B: predose, 0.5, 1.5, 4, 6, 12, 18, 24, 36, 48 and 72 h postdose.)
Population: All participants who received at least 1 dose of the study drug and had sufficient PK data to calculate Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Parts A and B) | PK: Maximum Concentration (Cmax) of LY2922083 | 2.36 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| 0.5 mg LY2922083 (Part A) | PK: Maximum Concentration (Cmax) of LY2922083 | 8.64 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| 1.5 mg LY2922083 (Part A) | PK: Maximum Concentration (Cmax) of LY2922083 | 20.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 29 |
| 5 mg LY2922083 (Part A) | PK: Maximum Concentration (Cmax) of LY2922083 | 66.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| 15 mg LY2922083 (Part A) | PK: Maximum Concentration (Cmax) of LY2922083 | 152 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| 50 mg LY2922083 (Part A) | PK: Maximum Concentration (Cmax) of LY2922083 | 327 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 67 |
| 150 mg LY2922083 (Parts A and B) | PK: Maximum Concentration (Cmax) of LY2922083 | 927 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
| 450 mg LY2922083 (Parts A and B) | PK: Maximum Concentration (Cmax) of LY2922083 | 1720 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
| 845 mg LY2922083 (Parts A and B) | PK: Maximum Concentration (Cmax) of LY2922083 | 407 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 131 |
| 450 mg LY2922083 (Part B) | PK: Maximum Concentration (Cmax) of LY2922083 | 808 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| 845 mg LY2922083 (Part B) | PK: Maximum Concentration (Cmax) of LY2922083 | 2220 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 73 |