A Study of LY3154885 in Healthy Participants

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to learn more about the safety and side effects of LY3154885 when given by mouth to healthy participants. The study will have up to four parts. Each participant will enroll in only one part. The study will last up to 70 days for each participant, including screening and follow-up.

Official Title
-----------------
Single- and Multiple-Ascending Dose, Safety, Tolerability, and Pharmacokinetic Study With LY3154885 in Healthy Subjects

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: LY3154885 - Capsule
* Drug: Placebo - Capsule
* Drug: Itraconazole
* Drug: LY3154885 - Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Are overtly healthy males or females, as determined by medical history and physical examination Male participants: Men, regardless of their fertility status, with partners who are nonpregnant women of childbearing potential, must agree to either remain abstinent (if this is their preferred and usual lifestyle) or use condoms with spermicide as well as 1 additional highly effective (<1% failure rate) method of contraception or effective method of contraception (such as diaphragms with spermicide) for 3 months following dosing Men with pregnant partners should use condoms with spermicide during intercourse for the duration of the study or for 3 months following dosing, whichever is longer Men who are in exclusively same-sex relationships (as their preferred and usual lifestyle) or with female partners of nonchildbearing potential are not required to use contraception Men should refrain from sperm donation for the duration of the study or for 3 months following the last dose of study drug, whichever is longer Female participants of nonchildbearing potential, including those who are: Infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, bilateral salpingectomy, confirmed tubal ligation, or tubal occlusion) or congenital anomaly such as Müllerian agenesis; or Postmenopausal, defined as 1 of the following: A woman at least 50 years of age with an intact uterus, not on hormone replacement therapy, who has had either: Cessation of menses for at least 1 year; or At least 6 months of spontaneous amenorrhea with a follicle-stimulating hormone level ≥40 milli-international units per milliliter (mIU/mL) at screening A woman at least 55 years of age, not on hormone replacement therapy, who has had at least 6 months of spontaneous amenorrhea; or A woman at least 55 years of age with a diagnosis of menopause prior to starting hormone replacement therapy Have a body mass index (BMI) of 18.0 to 35.0 kilograms per square meter (kg/m²), inclusive Exclusion Criteria: Have a marked baseline prolongation of/corrected QT (QTc) interval (for example, repeated demonstration of a QTcB interval >450 milliseconds [msec] for males or >470 msec for females); A history of additional risk factors for Torsades de Pointes (for example, heart failure, hypokalemia, family history of Long QT Syndrome); The use of concomitant medications that prolong the QT/QTc interval Have an abnormal blood pressure (BP) (taken after the participant has been in a supine position for at least 5 minutes) for the population, as determined by a systolic BP >140 millimeters of mercury (mmHg) or a diastolic BP >90 mmHg at screening or a preexisting history of hypertension. Up to 2 additional measurements may be taken after an appropriate resting interval at screening to confirm eligibility Have a significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (such as Cushing syndrome, hyperthyroidism, hyperaldosteronism), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational medicinal product (IMP); or of interfering with the interpretation of data Have a history of or current significant psychiatric disorders

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3154885 - Part A<br>LY3154885 administered orally in two of three study periods. | Drug: LY3154885 - Capsule<br>* Administered orally.<br>|
| Placebo Comparator: Placebo - Part A<br>Placebo administered orally in one of three study periods. | Drug: Placebo - Capsule<br>* Administered orally.<br>|
| Experimental: LY3154885 - Part B<br>LY3154885 administered orally alone. | Drug: LY3154885 - Capsule<br>* Administered orally.<br>|
| Placebo Comparator: Placebo - Part B<br>Placebo administered orally alone. | Drug: Placebo - Capsule<br>* Administered orally.<br>|
| Experimental: LY3154885 + Itraconazole - Part B<br>LY3154885 administered alone, orally, once. Itraconazole administered alone, orally, on consecutive days. LY3154885 co-administered with itraconazole, orally, once. | Drug: LY3154885 - Capsule<br>* Administered orally.<br>Drug: Itraconazole<br>* Administered orally.<br>|
| Placebo Comparator: Placebo + Itraconazole - Part B<br>Placebo administered alone, orally, once. Itraconazole administered alone, orally, on consecutive days. Placebo co-administered with itraconazole, orally, once. | Drug: Placebo - Capsule<br>* Administered orally.<br>Drug: Itraconazole<br>* Administered orally.<br>|
| Experimental: LY3154885 - Part C<br>LY3154885 administered orally on consecutive days. | Drug: LY3154885 - Capsule<br>* Administered orally.<br>|
| Placebo Comparator: Placebo - Part C<br>Placebo administered orally on consecutive days. | Drug: Placebo - Capsule<br>* Administered orally.<br>|
| Experimental: LY3154885 - Part D<br>LY3154885 administered orally once in each of three study periods. | Drug: LY3154885 - Capsule<br>* Administered orally.<br>Drug: LY3154885 - Tablet<br>* Administered orally.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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, will be reported in the Reported Adverse Events module | Baseline through Study Completion (up to 70 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3154885 | PK: Cmax of LY3154885 | Predose up to 96 hours postdose | 
| PK: Time to Cmax (Tmax) of LY3154885 | PK: Tmax of LY3154885 | Predose up to 96 hours postdose | 
| PK: Area Under the Concentration Versus Time Curve (AUC) of LY3154885 | PK: AUC of LY3154885 | Predose up to 96 hours postdose |