Healthy Volunteer
Conditions
Brief summary
To evaluate the safety and tolerability of LY3009104 when given orally as single and multiple doses in Japanese healthy subjects.
Interventions
DRUGPlacebo
Administered orally
DRUGLY3009104
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males or females. Male subjects: Agree to use 2 forms of highly effective methods of birth control with female partners of childbearing potential for the specified duration. Female subjects: Females must not be pregnant, breastfeeding, or at risk to become pregnant during study participation. Female subjects of childbearing potential must test negative for pregnancy at screening and agree to use 2 forms of highly effective methods of birth control, or remain abstinent for the specified duration. * Up to third generation Japanese, that is defined as all of the subject's biological grandparents are of exclusive Japanese decent and have been born in Japan. * Are between the body mass index (BMI) of 18.0 and 30.0 kg/m², inclusive at screening.
Exclusion criteria
* Are subjects who have previously completed or withdrawn from this study or any other study investigating LY3009104, and received the study drug. * Have a history of or current 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. * Show evidence of significant active neuropsychiatric disease. * Have current or recent history of herpes zoster or simplex in the last 90 days prior to randomization, or history of herpes zoster, such as disseminated herpes zoster involving multiple dermatomes, ocular involvement, including herpes zoster involving the ophthalmic branch of the trigeminal nerve. * Have or have a history of rheumatoid arthritis. * History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin. * History of stomach or intestinal surgery, except that appendectomy and/or cholecystectomy will be allowed. * Receipt of blood products within 2 months prior to study entry.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Effects | Days 1-10 for Cohorts 1 & 2, Days 1-7 for single dose of Cohorts 3 & 4, Days 8-31 for multiple doses | Adverse events were considered clinically significant effects. A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | Cmax of Day 1 is Cmax after single dose, and Cmax of Day 17 is Cmax at steady-state. |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104 | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | AUC is the measure of total plasma exposure of a drug over a given time period. AUC of Day 1 is AUC from 0 to 24 hours. AUC of Day 17 is AUC during one dosing interval at steady-state. |
| Pharmacokinetics: Half-Life(t1/2) of LY3009104 | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | Half life (t1/2) is the time measured for the plasma concentration of LY3009104 to decrease by one half. |
| Pharmacokinetics: Apparent Volume of Distribution of LY3009104 | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | Apparent volume of distribution is used to quantify the distribution of a drug between plasma and the rest of the body after dosing. It is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Day 1, it is apparent volume of distribution during the terminal phase after single dose. Day 17, it is apparent volume of distribution during the terminal phase at steady-state. |
| Pharmacokinetics: Apparent Total Body Clearance of LY3009104 | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 38 and 48 hours postdose | Apparent total body clearance is the volume of plasma from which the drug is completely removed in a given time period. For Day 1, it is apparent total body clearance of drug after single dose. For Day 17, it is apparent total body clearance of drug at steady-state. |
| Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax) | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 38 and 48 hours postdose | Tmax is time to reach maximum observed drug concentration. For Day 1, it is tmax after single dose. For Day 17, it is tmax at steady-state. |
| Pharmacokinetics: Renal Excretion of LY3009104 | Day 1: continuous for 24 hours | Percentage of LY3009104 excreted in urine from zero to 24 hours. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2 mg LY3009104 2 mg administered orally once on Day 1 (single dose) | 6 |
| 5 mg LY3009104 5 mg administered orally once on Day 1 (single dose) | 6 |
| 10 mg LY3009104 10 mg administered orally on Day 1 (single dose) and following a 7-day washout period, administered once daily for 10 days ((multiple dose) | 6 |
| 14 mg LY3009104 14 mg administered orally on Day 1 (single dose) and following a 7-day washout period, administered once daily for 10 days (multiple dose) | 7 |
| Placebo administered orally on Day 1 (single dose) and following a 7-day washout period, administered once daily for 10 days (multiple dose) | 9 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Entry criteria not met | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 2 mg LY3009104 | 5 mg LY3009104 | 10 mg LY3009104 | 14 mg LY3009104 | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 46.3 years STANDARD_DEVIATION 10.8 | 48.0 years STANDARD_DEVIATION 15 | 46.7 years STANDARD_DEVIATION 9 | 51.1 years STANDARD_DEVIATION 6.3 | 45.1 years STANDARD_DEVIATION 10.7 | 47.4 years STANDARD_DEVIATION 10.2 |
| Race/Ethnicity, Customized Asian | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 9 Participants | 34 Participants |
| Region of Enrollment United States | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 9 Participants | 34 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 7 Participants | 22 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 6 | 1 / 6 | 2 / 6 | 7 / 7 | 6 / 9 | 5 / 6 | 4 / 6 | 2 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 5 |
Outcome results
Primary
Number of Participants With Clinically Significant Effects
Adverse events were considered clinically significant effects. A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section.
Time frame: Days 1-10 for Cohorts 1 & 2, Days 1-7 for single dose of Cohorts 3 & 4, Days 8-31 for multiple doses
Population: Participants who were administered study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 2 mg LY3009104 Single Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| 2 mg LY3009104 Single Dose | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 1 Participants |
| 5 mg LY3009104 Single Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| 5 mg LY3009104 Single Dose | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 1 Participants |
| 10 mg LY3009104 Single Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| 10 mg LY3009104 Single Dose | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 2 Participants |
| 14 mg LY3009104 Single Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| 14 mg LY3009104 Single Dose | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 7 Participants |
| Placebo Single Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| Placebo Single Dose | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 6 Participants |
| 10 mg LY3009104 Multiple Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| 10 mg LY3009104 Multiple Dose | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 5 Participants |
| 14 mg LY3009104 Multiple Dose | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 4 Participants |
| 14 mg LY3009104 Multiple Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| Placebo Multiple Dose | Number of Participants With Clinically Significant Effects | Serious Adverse Events | 0 Participants |
| Placebo Multiple Dose | Number of Participants With Clinically Significant Effects | Nonserious Adverse Events | 2 Participants |
Secondary
Pharmacokinetics: Apparent Total Body Clearance of LY3009104
Apparent total body clearance is the volume of plasma from which the drug is completely removed in a given time period. For Day 1, it is apparent total body clearance of drug after single dose. For Day 17, it is apparent total body clearance of drug at steady-state.
Time frame: Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 38 and 48 hours postdose
Population: Participants who were administered study drug and had pharmacokinetics (PK) samples for the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 2 mg LY3009104 Single Dose | Pharmacokinetics: Apparent Total Body Clearance of LY3009104 | 12.9 Liter/hour (L/h) | Geometric Coefficient of Variation 11 |
| 5 mg LY3009104 Single Dose | Pharmacokinetics: Apparent Total Body Clearance of LY3009104 | 10.1 Liter/hour (L/h) | Geometric Coefficient of Variation 22 |
| 10 mg LY3009104 Single Dose | Pharmacokinetics: Apparent Total Body Clearance of LY3009104 | 14.8 Liter/hour (L/h) | Geometric Coefficient of Variation 20 |
| 14 mg LY3009104 Single Dose | Pharmacokinetics: Apparent Total Body Clearance of LY3009104 | 12.2 Liter/hour (L/h) | Geometric Coefficient of Variation 17 |
| Placebo Single Dose | Pharmacokinetics: Apparent Total Body Clearance of LY3009104 | 13.7 Liter/hour (L/h) | Geometric Coefficient of Variation 18 |
| 10 mg LY3009104 Multiple Dose | Pharmacokinetics: Apparent Total Body Clearance of LY3009104 | 12.3 Liter/hour (L/h) | Geometric Coefficient of Variation 17 |
Secondary
Pharmacokinetics: Apparent Volume of Distribution of LY3009104
Apparent volume of distribution is used to quantify the distribution of a drug between plasma and the rest of the body after dosing. It is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Day 1, it is apparent volume of distribution during the terminal phase after single dose. Day 17, it is apparent volume of distribution during the terminal phase at steady-state.
Time frame: Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose
Population: Participants who were administered study drug and had pharmacokinetics (PK) samples for the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 2 mg LY3009104 Single Dose | Pharmacokinetics: Apparent Volume of Distribution of LY3009104 | 96.3 Liter (L) | Geometric Coefficient of Variation 18 |
| 5 mg LY3009104 Single Dose | Pharmacokinetics: Apparent Volume of Distribution of LY3009104 | 99.4 Liter (L) | Geometric Coefficient of Variation 29 |
| 10 mg LY3009104 Single Dose | Pharmacokinetics: Apparent Volume of Distribution of LY3009104 | 138 Liter (L) | Geometric Coefficient of Variation 41 |
| 14 mg LY3009104 Single Dose | Pharmacokinetics: Apparent Volume of Distribution of LY3009104 | 150 Liter (L) | Geometric Coefficient of Variation 19 |
| Placebo Single Dose | Pharmacokinetics: Apparent Volume of Distribution of LY3009104 | 169 Liter (L) | Geometric Coefficient of Variation 24 |
| 10 mg LY3009104 Multiple Dose | Pharmacokinetics: Apparent Volume of Distribution of LY3009104 | 167 Liter (L) | Geometric Coefficient of Variation 23 |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104
AUC is the measure of total plasma exposure of a drug over a given time period. AUC of Day 1 is AUC from 0 to 24 hours. AUC of Day 17 is AUC during one dosing interval at steady-state.
Time frame: Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose
Population: Participants who were administered study drug and had pharmacokinetics (PK) samples for the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 2 mg LY3009104 Single Dose | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104 | 403 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 10 |
| 5 mg LY3009104 Single Dose | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104 | 1240 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 23 |
| 10 mg LY3009104 Single Dose | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104 | 1730 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 21 |
| 14 mg LY3009104 Single Dose | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104 | 2790 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 14 |
| Placebo Single Dose | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104 | 1970 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 18 |
| 10 mg LY3009104 Multiple Dose | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104 | 3060 nanomoles*hour/Liter (nmol*h/L) | Geometric Coefficient of Variation 17 |
Secondary
Pharmacokinetics: Half-Life(t1/2) of LY3009104
Half life (t1/2) is the time measured for the plasma concentration of LY3009104 to decrease by one half.
Time frame: Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose
Population: Participants who were administered study drug and had pharmacokinetics (PK) samples for the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 2 mg LY3009104 Single Dose | Pharmacokinetics: Half-Life(t1/2) of LY3009104 | 5.19 hour (h) |
| 5 mg LY3009104 Single Dose | Pharmacokinetics: Half-Life(t1/2) of LY3009104 | 6.82 hour (h) |
| 10 mg LY3009104 Single Dose | Pharmacokinetics: Half-Life(t1/2) of LY3009104 | 6.43 hour (h) |
| 14 mg LY3009104 Single Dose | Pharmacokinetics: Half-Life(t1/2) of LY3009104 | 8.48 hour (h) |
| Placebo Single Dose | Pharmacokinetics: Half-Life(t1/2) of LY3009104 | 8.57 hour (h) |
| 10 mg LY3009104 Multiple Dose | Pharmacokinetics: Half-Life(t1/2) of LY3009104 | 9.41 hour (h) |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104
Cmax of Day 1 is Cmax after single dose, and Cmax of Day 17 is Cmax at steady-state.
Time frame: Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose
Population: Participants who were administered study drug and had pharmacokinetics (PK) samples for the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 2 mg LY3009104 Single Dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 76.1 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 29 |
| 5 mg LY3009104 Single Dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 220 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 35 |
| 10 mg LY3009104 Single Dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 327 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 43 |
| 14 mg LY3009104 Single Dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 410 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 19 |
| Placebo Single Dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 319 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 30 |
| 10 mg LY3009104 Multiple Dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | 439 nanomoles/Liter (nmol/L) | Geometric Coefficient of Variation 9 |
Secondary
Pharmacokinetics: Renal Excretion of LY3009104
Percentage of LY3009104 excreted in urine from zero to 24 hours.
Time frame: Day 1: continuous for 24 hours
Population: Participants who were administered study drug (10 mg and 14 mg LY3009104 per protocol) and had pharmacokinetics (PK) samples for the analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 2 mg LY3009104 Single Dose | Pharmacokinetics: Renal Excretion of LY3009104 | 75.8 percentage of drug | Geometric Coefficient of Variation 7 |
| 5 mg LY3009104 Single Dose | Pharmacokinetics: Renal Excretion of LY3009104 | 63.6 percentage of drug | Geometric Coefficient of Variation 13 |
Secondary
Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax)
Tmax is time to reach maximum observed drug concentration. For Day 1, it is tmax after single dose. For Day 17, it is tmax at steady-state.
Time frame: Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 38 and 48 hours postdose
Population: Participants who were administered study drug and had pharmacokinetics (PK) samples for the analyses.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2 mg LY3009104 Single Dose | Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax) | 1.00 hour (h) |
| 5 mg LY3009104 Single Dose | Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax) | 1.00 hour (h) |
| 10 mg LY3009104 Single Dose | Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax) | 1.25 hour (h) |
| 14 mg LY3009104 Single Dose | Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax) | 1.00 hour (h) |
| Placebo Single Dose | Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax) | 1.00 hour (h) |
| 10 mg LY3009104 Multiple Dose | Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax) | 1.00 hour (h) |