Healthy
Conditions
Brief summary
The main purpose of this study in healthy participants is to learn more about the safety of LY3509754 and any side effects that might be associated with it. Blood tests will be performed to check how much LY3509754 gets into the bloodstream and how long it takes the body to eliminate it.
Interventions
DRUGLY3509754
Administered orally
DRUGPlacebo
Administered orally
DRUGItraconazole
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
* Overtly healthy males or females, as determined by medical history and physical examination. * Body mass index (BMI) within the range of 18 to 35 kilograms per meter squared (kg/m²) in Parts A, B, and C. In Part D (Japanese participants), body weight between 50 and 85 kg and BMI within the range of 18 to 28 kg/m².
Exclusion criteria
* Have previously completed or withdrawn from this study or any other study investigating LY3509754, and have previously received LY3509754. * Women of childbearing potential are excluded from the trial.
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 Day 26 | An SAE is any adverse event (AE) from the study that results in 1 of the following: Death, initial or prolonged inpatient hospitalization, a life-threatening experience (i.e., immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent 1 of the other outcomes listed in the definition above. 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 AEs, regardless of causality, will be reported in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | Part A: Pre-dose (P), 0.5,1,2,3,4,5,6,8,12,16,24,36,48,72,96 hours (h) post Day 1 dose. Part B: P,0.5,1,2,3,4,6,8,12,16,24,36,48,72,96 h post Day 1 dose; P,0.5,1,2,3,4,6,8,12,16,24,36,48,72,96,120,144,168 h Post Day 10 dose. | PK: Cmax of LY3509754 in Parts A and B. |
| PK: Cmax of LY3509754 in Parts C and D | Part C-Cohorts 1 and 3: P,0.5,1,2,3,4,6,8,12,16,24,48,72,96 h Post Day 14 dose. Part C-Cohort 2: P,0.5,1,2,3,4,5,6,8,12,16,24 h Post Day 14 dose. Part D: P,0.5,1,2,3,4,6,8,12,16,24,48,72,96 h Post Day 14 dose. | PK: Cmax of LY3509754 in Parts C and D. |
| PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | Part A: P, 0.5,1,2,3,4,5,6,8,12,16,24 h post Day 1 dose. Part B: P,0.5,1,2,3,4,6,8,12,16,24 h post Day 1 dose; P,0.5,1,2,3,4,6,8,12,16,24 h Post Day 10 dose. | PK: AUC(0-24) of LY3509754 in Parts A and B. |
| PK: AUC(0-24) of LY3509754 in Parts C and D | Part C-Cohorts 1 and 3: P,0.5,1,2,3,4,6,8,12,16,24 h Post Day 14 dose. Part C-Cohort 2: P,0.5,1,2,3,4,5,6,8,12,16,24 h Post Day 14 dose. Part D: P,0.5,1,2,3,4,6,8,12,16,24 h Post Day 14 dose. | PK: AUC(0-24) of LY3509754 in Parts C and D. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A - Placebo (Fasted) Participants received single oral dose of placebo under fasting condition. | 10 |
| Part A - Placebo (Fed) Participants received single oral dose of placebo under fed condition. | 2 |
| Part A - 10 mg LY3509754 (Fasted) Participants received a single oral dose of 10 mg LY3509754 under fasting condition. | 6 |
| Part A - 30 mg LY3509754 (Fasted) Participants received a single oral dose of 30 mg LY3509754 under fasting condition. | 6 |
| Part A - 100 mg LY3509754 (Fasted) Participants received a single oral dose of 100 mg LY3509754 under fasting condition. | 6 |
| Part A - 300 mg LY3509754 (Fasted and Fed) Participants received a single oral dose of 300 mg LY3509754 under fasting condition. There was a washout period of at least 5 days. Participants received a single oral dose of 300 mg LY3509754 under fed condition. | 9 |
| Part A - 1000 mg LY3509754 (Fasted) Participants received a single oral dose of 1000 mg LY3509754 under fasting condition. | 6 |
| Part A - 2000 mg LY3509754 (Fasted) Participants received a single oral dose of 2000 mg LY3509754 under fasting condition. | 6 |
| Part B - Placebo + 200 mg Itraconazole (Day 10) Participants received a single oral dose of placebo on Day 1 followed by daily doses of 200 mg itraconazole as oral solution for 10 days BID on Day 4 and QD from Days 5 through 13. Participants received a single oral dose of placebo on Day 10. | 3 |
| Part B - 10 mg LY3509754 + 200 mg Itraconazole (Day 10) Participants received a single oral dose of 10 mg LY3509754 on Day 1 followed by daily doses of 200 mg itraconazole as oral solution for 10 days BID on Day 4 and QD from Days 5 through 13. Participants received a single oral dose of placebo on Day 10. | 8 |
| Part C - Placebo QD [Cohorts 1 and 3] Participants received oral doses of placebo QD for 14 Days. | 4 |
| Part C - 100 mg LY3509754 QD [Cohort 1] Participants received oral doses of 100 mg LY3509754 QD for 14 Days. | 6 |
| Part C - Placebo QD + 1.2 mg Midazolam [Cohort 2] Participants received a single dose of 1.2 mg midazolam given as oral solution on Day -2 followed by oral doses of placebo QD from Day 1 to 15. Participants then received a single dose of 1.2 mg midazolam given as oral solution on Day 15. | 2 |
| Part C - 300 mg LY3509754 QD + 1.2 mg Midazolam [Cohort 2] Participants received a single dose of 1.2 mg midazolam given as oral solution on Day -2 followed by oral doses of 300 mg LY3509754 QD from Day 1 to 15. Participants then received a single dose of 1.2 mg midazolam given as oral solution on Day 15. | 8 |
| Part C - 1000 mg LY3509754 QD [Cohort 3] Participants received oral doses of 1000 mg LY3509754 QD for 14 Days. | 6 |
| Part D (Japanese) - Placebo QD Participants received oral doses of placebo QD for 14 Days. | 4 |
| Part D (Japanese) - 400 mg LY3509754 QD Participants received oral doses of 400 mg LY3509754 QD for 14 Days. | 6 |
| Part D (Japanese) - 1000 mg LY3509754 QD Participants received oral doses of 1000 mg LY3509754 QD for 14 Days. | 6 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part A - Placebo (Fed) | Part A - 10 mg LY3509754 (Fasted) | Part A - 30 mg LY3509754 (Fasted) | Part A - 100 mg LY3509754 (Fasted) | Part A - 300 mg LY3509754 (Fasted and Fed) | Part A - 1000 mg LY3509754 (Fasted) | Part A - 2000 mg LY3509754 (Fasted) | Part B - Placebo + 200 mg Itraconazole (Day 10) | Part A - Placebo (Fasted) | Part B - 10 mg LY3509754 + 200 mg Itraconazole (Day 10) | Part C - Placebo QD [Cohorts 1 and 3] | Part C - 100 mg LY3509754 QD [Cohort 1] | Part C - Placebo QD + 1.2 mg Midazolam [Cohort 2] | Part C - 300 mg LY3509754 QD + 1.2 mg Midazolam [Cohort 2] | Part C - 1000 mg LY3509754 QD [Cohort 3] | Part D (Japanese) - Placebo QD | Part D (Japanese) - 400 mg LY3509754 QD | Part D (Japanese) - 1000 mg LY3509754 QD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.45 years STANDARD_DEVIATION 12.13 | 43.5 years STANDARD_DEVIATION 3.5 | 43.8 years STANDARD_DEVIATION 16.1 | 43.8 years STANDARD_DEVIATION 11 | 52.0 years STANDARD_DEVIATION 10.4 | 52.9 years STANDARD_DEVIATION 13.3 | 56.8 years STANDARD_DEVIATION 4.6 | 42.0 years STANDARD_DEVIATION 14.3 | 33.3 years STANDARD_DEVIATION 6.8 | 49.4 years STANDARD_DEVIATION 13 | 42.6 years STANDARD_DEVIATION 9.4 | 44.0 years STANDARD_DEVIATION 8.5 | 43.2 years STANDARD_DEVIATION 15.3 | 38.0 years STANDARD_DEVIATION 2.8 | 46.5 years STANDARD_DEVIATION 16.1 | 48.2 years STANDARD_DEVIATION 12.2 | 52.5 years STANDARD_DEVIATION 11.9 | 54.0 years STANDARD_DEVIATION 7.5 | 50.0 years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 26 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 4 Participants | 4 Participants | 5 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 78 Participants | 2 Participants | 4 Participants | 5 Participants | 5 Participants | 5 Participants | 2 Participants | 1 Participants | 3 Participants | 9 Participants | 6 Participants | 3 Participants | 3 Participants | 1 Participants | 8 Participants | 5 Participants | 4 Participants | 6 Participants | 6 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 6 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 5 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 1 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 | 0 Participants | 0 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 44 Participants | 0 Participants | 3 Participants | 2 Participants | 3 Participants | 6 Participants | 4 Participants | 1 Participants | 0 Participants | 7 Participants | 4 Participants | 2 Participants | 4 Participants | 1 Participants | 4 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 104 Participants | 2 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 6 Participants | 6 Participants | 3 Participants | 10 Participants | 8 Participants | 4 Participants | 6 Participants | 2 Participants | 8 Participants | 6 Participants | 4 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 27 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 77 Participants | 2 Participants | 4 Participants | 5 Participants | 5 Participants | 6 Participants | 3 Participants | 4 Participants | 3 Participants | 7 Participants | 8 Participants | 3 Participants | 4 Participants | 1 Participants | 5 Participants | 6 Participants | 3 Participants | 4 Participants | 4 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 | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 11 | 0 / 8 | 0 / 8 | 0 / 4 | 0 / 6 | 0 / 10 | 0 / 2 | 0 / 8 | 0 / 2 | 0 / 8 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 10 | 1 / 2 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 9 | 2 / 9 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 4 / 11 | 0 / 8 | 1 / 8 | 1 / 4 | 2 / 6 | 1 / 10 | 0 / 2 | 2 / 8 | 1 / 2 | 0 / 8 | 2 / 6 | 2 / 4 | 4 / 6 | 4 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 9 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 11 | 0 / 8 | 0 / 8 | 0 / 4 | 0 / 6 | 0 / 10 | 0 / 2 | 0 / 8 | 0 / 2 | 0 / 8 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 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
An SAE is any adverse event (AE) from the study that results in 1 of the following: Death, initial or prolonged inpatient hospitalization, a life-threatening experience (i.e., immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent 1 of the other outcomes listed in the definition above. 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 AEs, regardless of causality, will be reported in the Reported Adverse Events module.
Time frame: Baseline up to Day 26
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A - Placebo (Fasted) | 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 - Placebo (Fed) | 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 - 10 Milligram (mg) LY3509754 (Fasted) | 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 - 30 mg LY3509754 (Fasted) | 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 - 100 mg LY3509754 (Fasted) | 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 - 300 mg LY3509754 (Fasted) | 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 - 300 mg LY3509754 (Fed) | 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 - 1000 mg LY3509754 (Fasted) | 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 - 2000 mg LY3509754 (Fasted) | 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 Alone (Day 1) | 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 + 200 mg Itraconazole (Day 10) | 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 - 200 mg Itraconazole (Days 4 to 13) | 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 - 10 mg LY3509754 Alone (Day 1) | 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 - 10 mg LY3509754 + 200 mg Itraconazole (Day 10) | 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 C - Placebo QD [Cohorts 1 and 3] | 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 C - 100 mg LY3509754 QD [Cohort 1] | 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 C - 1.2 mg Midazolam (Day -2) [Cohort 2] | 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 C - Placebo QD (Days 1 to 14) [Cohort 2] | 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 C - 300 mg LY3509754 QD (Days 1 to 14) [Cohort 2] | 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 C - Placebo QD + 1.2 mg Midazolam (Day 15) [Cohort 2] | 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 C - 300 mg LY3509754 QD + 1.2 mg Midazolam (Day 15) [Cohort 2] | 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 C - 1000 mg LY3509754 QD [Cohort 3] | 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 D (Japanese) - Placebo QD | 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 D (Japanese) - 400 mg LY3509754 QD | 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 D (Japanese) - 1000 mg LY3509754 QD | 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 Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B
PK: Cmax of LY3509754 in Parts A and B.
Time frame: Part A: Pre-dose (P), 0.5,1,2,3,4,5,6,8,12,16,24,36,48,72,96 hours (h) post Day 1 dose. Part B: P,0.5,1,2,3,4,6,8,12,16,24,36,48,72,96 h post Day 1 dose; P,0.5,1,2,3,4,6,8,12,16,24,36,48,72,96,120,144,168 h Post Day 10 dose.
Population: All participants who received at least one dose of LY3509754 or itraconazole and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo (Fasted) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 20.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| Part A - Placebo (Fed) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 49.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| Part A - 10 Milligram (mg) LY3509754 (Fasted) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 136 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 73 |
| Part A - 30 mg LY3509754 (Fasted) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 384 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 62 |
| Part A - 100 mg LY3509754 (Fasted) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 278 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 72 |
| Part A - 300 mg LY3509754 (Fasted) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 1390 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 55 |
| Part A - 300 mg LY3509754 (Fed) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 2310 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
| Part A - 1000 mg LY3509754 (Fasted) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 15.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| Part A - 2000 mg LY3509754 (Fasted) | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3509754 in Parts A and B | 43.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
Secondary
PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B
PK: AUC(0-24) of LY3509754 in Parts A and B.
Time frame: Part A: P, 0.5,1,2,3,4,5,6,8,12,16,24 h post Day 1 dose. Part B: P,0.5,1,2,3,4,6,8,12,16,24 h post Day 1 dose; P,0.5,1,2,3,4,6,8,12,16,24 h Post Day 10 dose.
Population: All participants who received at least one dose of LY3509754 or itraconazole and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo (Fasted) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 153 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 20 |
| Part A - Placebo (Fed) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 375 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
| Part A - 10 Milligram (mg) LY3509754 (Fasted) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 1340 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 60 |
| Part A - 30 mg LY3509754 (Fasted) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 3930 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 45 |
| Part A - 100 mg LY3509754 (Fasted) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 2930 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 69 |
| Part A - 300 mg LY3509754 (Fasted) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 14900 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 42 |
| Part A - 300 mg LY3509754 (Fed) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 26300 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 29 |
| Part A - 1000 mg LY3509754 (Fasted) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 135 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 29 |
| Part A - 2000 mg LY3509754 (Fasted) | PK: Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose AUC(0-24) of LY3509754 in Parts A and B | 596 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 33 |
Secondary
PK: AUC(0-24) of LY3509754 in Parts C and D
PK: AUC(0-24) of LY3509754 in Parts C and D.
Time frame: Part C-Cohorts 1 and 3: P,0.5,1,2,3,4,6,8,12,16,24 h Post Day 14 dose. Part C-Cohort 2: P,0.5,1,2,3,4,5,6,8,12,16,24 h Post Day 14 dose. Part D: P,0.5,1,2,3,4,6,8,12,16,24 h Post Day 14 dose.
Population: All participants who received at least one dose of LY3509754 or midazolam and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo (Fasted) | PK: AUC(0-24) of LY3509754 in Parts C and D | 2170 ng*h/mL | Geometric Coefficient of Variation 41 |
| Part A - Placebo (Fed) | PK: AUC(0-24) of LY3509754 in Parts C and D | 4050 ng*h/mL | Geometric Coefficient of Variation 38 |
| Part A - 10 Milligram (mg) LY3509754 (Fasted) | PK: AUC(0-24) of LY3509754 in Parts C and D | 12200 ng*h/mL | Geometric Coefficient of Variation 42 |
| Part A - 30 mg LY3509754 (Fasted) | PK: AUC(0-24) of LY3509754 in Parts C and D | 7560 ng*h/mL | Geometric Coefficient of Variation 30 |
| Part A - 100 mg LY3509754 (Fasted) | PK: AUC(0-24) of LY3509754 in Parts C and D | 18000 ng*h/mL | Geometric Coefficient of Variation 22 |
Secondary
PK: Cmax of LY3509754 in Parts C and D
PK: Cmax of LY3509754 in Parts C and D.
Time frame: Part C-Cohorts 1 and 3: P,0.5,1,2,3,4,6,8,12,16,24,48,72,96 h Post Day 14 dose. Part C-Cohort 2: P,0.5,1,2,3,4,5,6,8,12,16,24 h Post Day 14 dose. Part D: P,0.5,1,2,3,4,6,8,12,16,24,48,72,96 h Post Day 14 dose.
Population: All participants who received at least one dose of LY3509754 or midazolam and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A - Placebo (Fasted) | PK: Cmax of LY3509754 in Parts C and D | 218 ng/mL | Geometric Coefficient of Variation 52 |
| Part A - Placebo (Fed) | PK: Cmax of LY3509754 in Parts C and D | 458 ng/mL | Geometric Coefficient of Variation 50 |
| Part A - 10 Milligram (mg) LY3509754 (Fasted) | PK: Cmax of LY3509754 in Parts C and D | 1160 ng/mL | Geometric Coefficient of Variation 55 |
| Part A - 30 mg LY3509754 (Fasted) | PK: Cmax of LY3509754 in Parts C and D | 805 ng/mL | Geometric Coefficient of Variation 30 |
| Part A - 100 mg LY3509754 (Fasted) | PK: Cmax of LY3509754 in Parts C and D | 2050 ng/mL | Geometric Coefficient of Variation 31 |