Healthy
Conditions
Brief summary
The main purpose of this study is to evaluate the safety and tolerability of LY3337641 in healthy Japanese and Caucasian participants. The study will also investigate how the body processes LY3337641 and the effect of LY3337641 on the body. The study will last up to 4 weeks for each participant. Screening may occur within 28 days prior to first dose of study drug.
Interventions
DRUGLY3337641
Administered orally.
DRUGPlacebo
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy Japanese or Caucasian * Body mass index (BMI) 18.0 - 32.0 kilograms per square meter (kg/m²)
Exclusion criteria
* Are currently enrolled in a clinical trial involving an investigational product or off-label use of a drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Have participated, within the last 30 days, in a clinical trial involving an investigational product. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer, if known) should have passed * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study or affects or confounds the QTc analysis or have Fridericia-corrected QT interval (QTcF) \>450 milliseconds (msec) for males and \>470 msec for females * Have had symptomatic herpes zoster within 3 months of screening * Have active or latent tuberculosis (TB) based on a positive medical history, examination, and/or TB test results. * Have received live vaccine(s) within 1 month of screening or intend to during the study * Are immunocompromised * Have a history of constipation or have had acute constipation within 3 weeks prior to admission
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Up To 31 Days | Clinically significant events were defined as serious adverse events (SAE). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3337641 | MD: Day 1 pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose,Day 15 pre-dose,0.25,0.5,1,2,3,4,6,8,10,12,24,36,48,96,168,240 and 336 hours post-dose. SD: pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12,24,36,48,168 and 336 hours post-dose | Cmax of LY3337641 was evaluated. |
| PK: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of LY3337641 | MD: Day 1 pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose,Day 15 pre-dose,0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose. SD: pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose | AUC from zero to 24-hour of LY3337641 was evaluated. |
| PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of LY3337641 | MD: Day 1 pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose,Day 15 pre-dose,0.25,0.5,1,2,3,4,6,8,10,12,24,36,48,96,168,240 and 336 hours post-dose. SD: pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12,24,36,48,168 and 336 hours post-dose | AUC from zero to infinity of LY3337641 was evaluated. For 30mg LY3337641 MD Day 1, pharmacokinetic data up to 24-hour post-dose were used for pharmacokinetic parameters calculation. |
Countries
United States
Participant flow
Pre-assignment details
The study consisted of multiple-doses (MD) in Cohort 1 and single-dose (SD) for Cohorts 2, 3, and 4.
Participants by arm
| Arm | Count |
|---|---|
| Placebo SD Participants received single oral dose of placebo tablet with a two week follow-up period. | 6 |
| 5 mg LY3337641 SD Participants received single oral dose of 5 mg LY3337641 tablet with a two week follow-up period. | 6 |
| 80 mg LY3337641 SD Participants received single oral dose of 80 mg LY3337641 tablet with a two week follow-up period. | 6 |
| 160 mg LY3337641 SD Participants received single oral dose of 160 mg LY3337641 tablet with a two week follow-up period. | 6 |
| Placebo MD Participants received multiple oral doses of placebo tablet once daily for two weeks with a two week follow-up period. | 3 |
| 30 mg LY3337641 MD Participants received multiple oral doses of 30 mg LY3337641 tablet once daily for two weeks with a two week follow-up period. | 9 |
| Total | 36 |
Baseline characteristics
| Characteristic | 30 mg LY3337641 MD | Placebo SD | 5 mg LY3337641 SD | Total | 80 mg LY3337641 SD | 160 mg LY3337641 SD | Placebo MD |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 40.8 years STANDARD_DEVIATION 12.5 | 42.2 years STANDARD_DEVIATION 11.5 | 44.5 years STANDARD_DEVIATION 10.1 | 43.0 years STANDARD_DEVIATION 11.1 | 46.7 years STANDARD_DEVIATION 11.6 | 45.5 years STANDARD_DEVIATION 12 | 36.0 years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 6 Participants | 6 Participants | 35 Participants | 6 Participants | 6 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 6 Participants | 3 Participants | 3 Participants | 20 Participants | 3 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 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 |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 3 Participants | 16 Participants | 3 Participants | 3 Participants | 1 Participants |
| Region of Enrollment United States | 9 Participants | 6 Participants | 6 Participants | 36 Participants | 6 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 2 Participants | 15 Participants | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 4 Participants | 21 Participants | 4 Participants | 2 Participants | 1 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 9 |
| other Total, other adverse events | 1 / 6 | 0 / 6 | 1 / 6 | 2 / 6 | 3 / 3 | 6 / 9 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 9 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Clinically significant events were defined as serious adverse events (SAE). A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Up To 31 Days
Population: All participants who received at least one dose of LY3337641 or placebo, and have at least one post-dose safety assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo SD | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 5 mg LY3337641 SD | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 80 mg LY3337641 SD | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 160 mg LY3337641 SD | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| Placebo MD | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 30 mg LY3337641 MD | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3337641
Cmax of LY3337641 was evaluated.
Time frame: MD: Day 1 pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose,Day 15 pre-dose,0.25,0.5,1,2,3,4,6,8,10,12,24,36,48,96,168,240 and 336 hours post-dose. SD: pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12,24,36,48,168 and 336 hours post-dose
Population: All participants who received at least 1 dose of LY3337641 and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SD | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3337641 | 11.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| 5 mg LY3337641 SD | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3337641 | 56.5 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
| 80 mg LY3337641 SD | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3337641 | 186 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| 160 mg LY3337641 SD | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3337641 | 358 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 37 |
| Placebo MD | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3337641 | 65.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 54 |
Secondary
PK: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of LY3337641
AUC from zero to 24-hour of LY3337641 was evaluated.
Time frame: MD: Day 1 pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose,Day 15 pre-dose,0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose. SD: pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose
Population: All participants who received at least one dose of LY3337641 and have evaluable PK data
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of LY3337641 | 84.8 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 58 |
| 5 mg LY3337641 SD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of LY3337641 | 276 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 59 |
| 80 mg LY3337641 SD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of LY3337641 | 1040 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| 160 mg LY3337641 SD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of LY3337641 | 2100 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 47 |
| Placebo MD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of LY3337641 | 368 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 65 |
Secondary
PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of LY3337641
AUC from zero to infinity of LY3337641 was evaluated. For 30mg LY3337641 MD Day 1, pharmacokinetic data up to 24-hour post-dose were used for pharmacokinetic parameters calculation.
Time frame: MD: Day 1 pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12 and 24 hours post-dose,Day 15 pre-dose,0.25,0.5,1,2,3,4,6,8,10,12,24,36,48,96,168,240 and 336 hours post-dose. SD: pre-dose, 0.25,0.5,1,2,3,4,6,8,10,12,24,36,48,168 and 336 hours post-dose
Population: All participants who received at least one dose of LY3337641 and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo SD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of LY3337641 | 92.0 ng*hr/mL | Geometric Coefficient of Variation 62 |
| 5 mg LY3337641 SD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of LY3337641 | 283 ng*hr/mL | Geometric Coefficient of Variation 61 |
| 80 mg LY3337641 SD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of LY3337641 | 1060 ng*hr/mL | Geometric Coefficient of Variation 27 |
| 160 mg LY3337641 SD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of LY3337641 | 2150 ng*hr/mL | Geometric Coefficient of Variation 48 |
| Placebo MD | PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of LY3337641 | 382 ng*hr/mL | Geometric Coefficient of Variation 68 |