Healthy
Conditions
Brief summary
The main purpose of this study in healthy participants is to learn more about the safety of LY3522348 and any side effects that might be associated with it. Blood tests will be performed to check how much LY3522348 gets into the bloodstream and how long it takes the body to eliminate it. This study has two parts: Part A will last up to about six weeks and Part B will last up to about eight weeks for each participant.
Interventions
DRUGLY3522348
Administered orally.
DRUGPlacebo
Administered orally.
DRUGMidazolam
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy as determined through medical evaluation including medical history and physical examination * Have a body mass index of 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 one month prior to screening and enrollment (less than \[\<\]5 percent \[%\] body weight change) and have not received dietary intervention in the one month prior to screening and enrollment * Have safety laboratory test results within normal reference range for the population or investigative site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
Exclusion criteria
* 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 data analysis * Have blood pressure of 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 * Have a history of fructosuria * Use of any drugs or substances that are known strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A) is specifically excluded within 14 days prior to the first administration of study intervention 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 | Part A: Baseline up to Day 14; Part B: Baseline up to Day 28 | An SAE is any untoward medical occurrence temporally associated with the use of study intervention that results in death is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as determined by investigator. The number of participants with one or more SAEs considered by the investigator to be related to study drug administration is reported here. A summary of SAEs and other non-serious adverse events, regardless of causality, will be reported in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | Day 1 (Predose, 0.75, 1.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours post Day 1 dose) | PK: AUC(0-tlast) of LY3522348 |
| Part B PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | Day 1 (Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16, 24 hours post Day 1 dose); Day 14 (Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 144 hours post Day 14 dose) | PK: AUC(0-tlast) of LY3522348 |
| Part A PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | Day 1 (Predose, 0.75, 1.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours post Day 1 dose) | PK: Cmax of LY3522348 |
| Part B PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | Day 1 (Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16, 24 hours post Day 1 dose); Day 14 (Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 144 hours post Day 14 dose) | PK: Cmax of LY3522348 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A: Placebo A single dose of Placebo administered orally on Day 1. | 10 |
| Part A: 5 mg LY3522348 A single dose of 5 mg LY3522348 administered orally on Day 1. | 6 |
| Part A: 15 mg LY3522348 A single dose of 15 mg LY3522348 administered orally on Day 1. | 6 |
| Part A: 50 mg LY3522348 A single dose of 50 mg LY3522348 administered orally on Day 1. | 6 |
| Part A: 150 mg LY3522348 A single dose of 150 mg LY3522348 administered orally on Day 1. | 6 |
| Part A: 380 mg LY3522348 A single dose of 380 mg LY3522348 administered orally on Day 1. | 6 |
| Part B: Placebo Placebo administered orally once daily on Days 1-14. | 4 |
| Part B: Placebo + Midazolam Placebo administered orally once daily on Days 1-15 and a single dose of 200 μg Midazolam administered orally on Days -1 and 15. | 2 |
| Part B: 50 mg LY3522348 50 mg LY3522348 administered orally once daily on Days 1-14. | 6 |
| Part B: 120 mg LY3522348 120 mg LY3522348 administered orally once daily on Days 1-14. | 6 |
| Part B: 290 mg LY3522348 + Midazolam 290 mg LY3522348 administered orally once daily on Days 1-15 and a single dose of 200 μg Midazolam administered orally on Days -1 and 15. | 7 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part A: Placebo | Part A: 5 mg LY3522348 | Part A: 15 mg LY3522348 | Part A: 50 mg LY3522348 | Part A: 150 mg LY3522348 | Part A: 380 mg LY3522348 | Part B: Placebo | Part B: Placebo + Midazolam | Part B: 50 mg LY3522348 | Part B: 120 mg LY3522348 | Part B: 290 mg LY3522348 + Midazolam | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.2 years | 53.5 years | 48.8 years | 56.0 years | 57.0 years | 31.0 years | 47.5 years | 57.0 years | 43.0 years | 36.3 years | 45.0 years | 47.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 4 Participants | 4 Participants | 5 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants | 6 Participants | 42 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 |
| 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 |
| 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 |
| Race (NIH/OMB) Black or African American | 5 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 4 Participants | 26 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 |
| 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 |
| 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 |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 3 Participants | 39 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 5 Participants | 3 Participants | 4 Participants | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 26 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 6 Participants | 2 Participants | 1 Participants | 4 Participants | 5 Participants | 6 Participants | 39 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 7 |
| other Total, other adverse events | 1 / 10 | 2 / 6 | 1 / 6 | 1 / 6 | 3 / 6 | 1 / 6 | 0 / 4 | 0 / 2 | 0 / 6 | 3 / 6 | 1 / 7 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 7 |
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
An SAE is any untoward medical occurrence temporally associated with the use of study intervention that results in death is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation as determined by investigator. The number of participants with one or more SAEs considered by the investigator to be related to study drug administration is reported here. A summary of SAEs and other non-serious adverse events, regardless of causality, will be reported in the Reported Adverse Events module.
Time frame: Part A: Baseline up to Day 14; Part B: Baseline up to Day 28
Population: All enrolled participants, irrespective of the completion of all protocol requirements.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | 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 |
| Part A: 5 mg LY3522348 | 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 |
| Part A: 15 mg LY3522348 | 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 |
| Part A: 50 mg LY3522348 | 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 |
| Part A: 150 mg LY3522348 | 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 |
| Part A: 380 mg LY3522348 | 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 |
| Part B: Placebo | 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 |
| Part B: Placebo + Midazolam | 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 |
| Part B: 50 mg LY3522348 | 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 |
| Part B: 120 mg LY3522348 | 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 |
| Part B: 290 mg LY3522348 + Midazolam | 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
Part A Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348
PK: AUC(0-tlast) of LY3522348
Time frame: Day 1 (Predose, 0.75, 1.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours post Day 1 dose)
Population: All enrolled participants in Part A who received at least one dose of study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | 0.330 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 25 |
| Part A: 5 mg LY3522348 | Part A Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | 1.27 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 30 |
| Part A: 15 mg LY3522348 | Part A Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | 3.37 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 20 |
| Part A: 50 mg LY3522348 | Part A Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | 9.45 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 37 |
| Part A: 150 mg LY3522348 | Part A Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | 25.3 microgram*hour/milliliter (μg*h/mL) | Geometric Coefficient of Variation 24 |
Secondary
Part A PK: Maximum Observed Drug Concentration (Cmax) of LY3522348
PK: Cmax of LY3522348
Time frame: Day 1 (Predose, 0.75, 1.5, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, 96, 144 hours post Day 1 dose)
Population: All enrolled participants in Part A who received at least one dose of study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | 0.00964 micrograms/mililiter (μg/mL) | Geometric Coefficient of Variation 17 |
| Part A: 5 mg LY3522348 | Part A PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | 0.0399 micrograms/mililiter (μg/mL) | Geometric Coefficient of Variation 23 |
| Part A: 15 mg LY3522348 | Part A PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | 0.113 micrograms/mililiter (μg/mL) | Geometric Coefficient of Variation 23 |
| Part A: 50 mg LY3522348 | Part A PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | 0.323 micrograms/mililiter (μg/mL) | Geometric Coefficient of Variation 39 |
| Part A: 150 mg LY3522348 | Part A PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | 0.897 micrograms/mililiter (μg/mL) | Geometric Coefficient of Variation 18 |
Secondary
Part B PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348
PK: AUC(0-tlast) of LY3522348
Time frame: Day 1 (Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16, 24 hours post Day 1 dose); Day 14 (Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 144 hours post Day 14 dose)
Population: All enrolled participants in Part B who received at least one dose of study drug and have evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | Day 1 | 1.76 μg*h/mL | Geometric Coefficient of Variation 25 |
| Part A: Placebo | Part B PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | Day 14 | 6.00 μg*h/mL | Geometric Coefficient of Variation 29 |
| Part A: 5 mg LY3522348 | Part B PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | Day 1 | 5.03 μg*h/mL | Geometric Coefficient of Variation 18 |
| Part A: 5 mg LY3522348 | Part B PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | Day 14 | 14.4 μg*h/mL | Geometric Coefficient of Variation 31 |
| Part A: 15 mg LY3522348 | Part B PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | Day 1 | 11.1 μg*h/mL | Geometric Coefficient of Variation 25 |
| Part A: 15 mg LY3522348 | Part B PK: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC(0-tlast)) of LY3522348 | Day 14 | 20.4 μg*h/mL | Geometric Coefficient of Variation 22 |
Secondary
Part B PK: Maximum Observed Drug Concentration (Cmax) of LY3522348
PK: Cmax of LY3522348
Time frame: Day 1 (Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16, 24 hours post Day 1 dose); Day 14 (Predose, 0.75, 1.5, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, 144 hours post Day 14 dose)
Population: All enrolled participants in Part B who received at least one dose of study drug and have evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | Day 1 | 0.109 μg/mL | Geometric Coefficient of Variation 29 |
| Part A: Placebo | Part B PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | Day 14 | 0.188 μg/mL | Geometric Coefficient of Variation 25 |
| Part A: 5 mg LY3522348 | Part B PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | Day 1 | 0.330 μg/mL | Geometric Coefficient of Variation 15 |
| Part A: 5 mg LY3522348 | Part B PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | Day 14 | 0.464 μg/mL | Geometric Coefficient of Variation 15 |
| Part A: 15 mg LY3522348 | Part B PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | Day 1 | 0.690 μg/mL | Geometric Coefficient of Variation 13 |
| Part A: 15 mg LY3522348 | Part B PK: Maximum Observed Drug Concentration (Cmax) of LY3522348 | Day 14 | 1.15 μg/mL | Geometric Coefficient of Variation 22 |