Healthy
Conditions
Brief summary
The main purpose of this study in healthy participants is to learn more about the safety of LY3478045 and any side effects that might be associated with it. The study will also measure how much LY3478045 gets into the bloodstream and how long it takes the body to get rid of it. This study has two parts: Part A (one dose) will last about six weeks and Part B (more than one dose) will last about eight weeks for each participant.
Interventions
DRUGLY3478045
Administered orally.
DRUGPlacebo
Administered orally.
DRUGAtorvastatin
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
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy participants as determined through medical history and physical examination * Have a body mass index greater than or equal to (≥)18.5 and less than or equal to (≤)40 kilograms per square meter (kg/m²) * Have had a stable weight for 3 months prior to screening and enrollment (less than \[\<\]5 percent \[%\] body weight change) and have not received dietary intervention in the 3 months prior to screening and enrollment * Have safety laboratory test results within the normal reference range for the population or investigative site, or results with acceptable deviations that are judged as not clinically significant by the investigator
Exclusion criteria
* Have a history of fructosuria * Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participating in the study or may confound ECG (QT) data analysis * Have blood pressure greater than (\>)160/90 millimeters of mercury (mmHg) and pulse rate \<50 or \>100 beats per minute (bpm), supine (at screening), or with minor deviations judged to be acceptable by the investigator * Use of any drugs or substances that are known strong inducers or inhibitors of cytochrome P450 (CYP)3A or organic anion-transporting polypeptides (OATPs) are specifically excluded within 14 days prior to the first administration of study drug and during the study
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 | Baseline Up to Final Follow-up: Up to 14 Days (Part A) and up to 28 Days (Part B) | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, is reported in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | Part A: Predose, 0.75, 1.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72 and 95 hours post dose; Part B: Day 1: Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16 and 24 hours post dose; Day 14: Predose ,0.75, 1.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose | PK: AUC(0-inf) of LY3478045 was reported. |
| PK: Maximum Concentration (Cmax) of LY3478045 | Part A: Predose, 0.75, 1.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72 and 95 hours post dose; Part B: Day 1: Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16 and 24 hours post dose; Day 14: Predose ,0.75, 1.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose | PK: Cmax of LY3478045 was reported. |
Countries
United States
Participant flow
Pre-assignment details
The study included two parts (Part A and Part B). A single ascending oral dose of LY3478045 was administered in Part A, and multiple ascending oral doses of LY3478045 were administered once daily (QD) in Part B. Participants in a few reporting arms of Part B received a 40-milligram (mg) oral dose of atorvastatin 4 hours after breakfast on Day -2 and 4 hours after LY3478045 administration on Day 7.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (Part A) Participants received single oral dose of placebo on Day 1. | 10 |
| 20 mg LY3478045 (Part A) Participants received single oral dose of 20 mg LY3478045 on Day 1. | 6 |
| 60 mg LY3478045 (Part A) Participants received single oral dose of 60 mg LY3478045 on Day 1. | 6 |
| 180 mg LY3478045 (Part A) Participants received single oral dose of 180 mg LY3478045 on Day 1. | 6 |
| 500 mg LY3478045 (Part A) Participants received single oral dose of 500 mg LY3478045 on Day 1. | 6 |
| 700 mg LY3478045 (Part A) Participants received single oral dose of 700 mg LY3478045 on Day 1. | 6 |
| Placebo QD (Part B) Participants received oral dose of placebo QD for 14 days. | 4 |
| Placebo QD + 40 mg Atorvastatin (Part B) Participants received oral dose of placebo QD for 14 days and 40 mg atorvastatin administered orally 4 hours after breakfast on Day -2 and 4 hours after LY3478045 administration on Day 7. | 4 |
| 60 mg LY3478045 QD (Part B) Participants received oral dose of 60 mg LY3478045 QD for 14 days. | 6 |
| 160 mg LY3478045 QD + 40 mg Atorvastatin (Part B) Participants received oral dose of 160 mg LY3478045 QD for 14 days and 40 mg atorvastatin administered orally 4 hours after breakfast on Day -2 and 4 hours after LY3478045 administration on Day 7. | 6 |
| 300 mg LY3478045 QD (Part B) Participants received oral dose of 300 mg LY3478045 QD for 14 days. | 6 |
| 360 mg LY3478045 QD + 40 mg Atorvastatin (Part B) Participants received oral dose of 360 mg LY3478045 for 14 days and 40 mg atorvastatin administered orally 4 hours after breakfast on Day -2 and 4 hours after LY3478045 administration on Day 7. | 6 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo (Part A) | Total | 360 mg LY3478045 QD + 40 mg Atorvastatin (Part B) | 300 mg LY3478045 QD (Part B) | 160 mg LY3478045 QD + 40 mg Atorvastatin (Part B) | 60 mg LY3478045 QD (Part B) | Placebo QD + 40 mg Atorvastatin (Part B) | Placebo QD (Part B) | 700 mg LY3478045 (Part A) | 500 mg LY3478045 (Part A) | 180 mg LY3478045 (Part A) | 60 mg LY3478045 (Part A) | 20 mg LY3478045 (Part A) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 43.9 years STANDARD_DEVIATION 9.4 | 44.9 years STANDARD_DEVIATION 10.7 | 54.8 years STANDARD_DEVIATION 6.4 | 48.0 years STANDARD_DEVIATION 9.6 | 36.5 years STANDARD_DEVIATION 9.9 | 35.8 years STANDARD_DEVIATION 12.8 | 48.3 years STANDARD_DEVIATION 7.5 | 52.0 years STANDARD_DEVIATION 4.7 | 50.5 years STANDARD_DEVIATION 9.6 | 47.8 years STANDARD_DEVIATION 7.6 | 42.3 years STANDARD_DEVIATION 9.1 | 40.2 years STANDARD_DEVIATION 13.7 | 43.0 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 27 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 45 Participants | 4 Participants | 3 Participants | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 5 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 | 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) Black or African American | 3 Participants | 29 Participants | 1 Participants | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 3 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 | 1 Participants | 0 Participants | 0 Participants | 1 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 | 7 Participants | 42 Participants | 5 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 4 Participants | 5 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 10 Participants | 72 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 4 Participants | 35 Participants | 6 Participants | 6 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 37 Participants | 0 Participants | 0 Participants | 6 Participants | 4 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 5 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 2 / 10 | 1 / 6 | 0 / 6 | 2 / 6 | 1 / 6 | 1 / 6 | 1 / 4 | 2 / 4 | 0 / 6 | 0 / 6 | 1 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 |
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
A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, is reported in the Reported Adverse Events module.
Time frame: Baseline Up to Final Follow-up: Up to 14 Days (Part A) and up to 28 Days (Part B)
Population: All enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo (Part A) | 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 |
| 20 mg LY3478045 (Part A) | 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 |
| 60 mg LY3478045 (Part A) | 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 |
| 180 mg LY3478045 (Part A) | 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 |
| 500 mg LY3478045 (Part A) | 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 |
| 700 mg LY3478045 (Part A) | 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 QD (Part B) | 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 QD + 40 mg Atorvastatin (Part B) | 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 |
| 60 mg LY3478045 QD (Part B) | 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 LY3478045 QD + 40 mg Atorvastatin (Part B) | 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 |
| 300 mg LY3478045 QD (Part B) | 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 |
| 360 mg LY3478045 QD + 40 mg Atorvastatin (Part B) | 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): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045
PK: AUC(0-inf) of LY3478045 was reported.
Time frame: Part A: Predose, 0.75, 1.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72 and 95 hours post dose; Part B: Day 1: Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16 and 24 hours post dose; Day 14: Predose ,0.75, 1.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 7410 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 38 |
| 20 mg LY3478045 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 24300 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 51 |
| 60 mg LY3478045 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 59900 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 32 |
| 180 mg LY3478045 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 275000 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 39 |
| 500 mg LY3478045 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 382000 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 19 |
| 700 mg LY3478045 (Part A) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 67800 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 154 |
| Placebo QD (Part B) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 98900 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 37 |
| Placebo QD + 40 mg Atorvastatin (Part B) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 388000 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 71 |
| 60 mg LY3478045 QD (Part B) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3478045 | 484000 nanogram*hour per milliliter (ng*h/ mL) | Geometric Coefficient of Variation 48 |
Secondary
PK: Maximum Concentration (Cmax) of LY3478045
PK: Cmax of LY3478045 was reported.
Time frame: Part A: Predose, 0.75, 1.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72 and 95 hours post dose; Part B: Day 1: Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16 and 24 hours post dose; Day 14: Predose ,0.75, 1.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo (Part A) | PK: Maximum Concentration (Cmax) of LY3478045 | 303 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| 20 mg LY3478045 (Part A) | PK: Maximum Concentration (Cmax) of LY3478045 | 1280 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| 60 mg LY3478045 (Part A) | PK: Maximum Concentration (Cmax) of LY3478045 | 3670 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| 180 mg LY3478045 (Part A) | PK: Maximum Concentration (Cmax) of LY3478045 | 14500 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| 500 mg LY3478045 (Part A) | PK: Maximum Concentration (Cmax) of LY3478045 | 18500 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| 700 mg LY3478045 (Part A) | PK: Maximum Concentration (Cmax) of LY3478045 | 2360 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| Placebo QD (Part B) | PK: Maximum Concentration (Cmax) of LY3478045 | 5920 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| Placebo QD + 40 mg Atorvastatin (Part B) | PK: Maximum Concentration (Cmax) of LY3478045 | 19500 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
| 60 mg LY3478045 QD (Part B) | PK: Maximum Concentration (Cmax) of LY3478045 | 22400 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |