Healthy
Conditions
Brief summary
The main purpose of this study is to learn more about the safety and side effects of LY3526318 when given by mouth to healthy participants. The study will have two parts. Each participant will enroll in only one part. For each participant, Part A will last up to 28 days and Part B will last up to 51 days, including screening and follow-up.
Interventions
DRUGLY3526318
Administered orally
DRUGPlacebo
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
Part A Cohorts: \- Healthy male participants (including self-reported surgically sterile males) must agree to the following: * When engaging in sex with Women of Child-Bearing Potential (WOCBP) both the male participant and his female partner must use highly effective contraception consisting of 2 forms of birth control (1 of which must be a male barrier method such as a latex or polyurethane condom) from start of dosing throughout the clinical study period, and for 90 days after the final study drug administration * Nonsurgically sterile male participants must not donate sperm at any time from start of dosing until 90 days beyond the administration of study drug All Part A and Part B Cohorts: * Female participants must be nonpregnant and not lactating, or of nonchildbearing potential (either surgically sterilized \[e.g. tubal occlusion, hysterectomy, bilateral salpingectomy\] or physiologically incapable of becoming pregnant, or postmenopausal with amenorrhea for at least 12 consecutive months). Healthy female participants of child-bearing potential who have a fertile male sexual partner must be willing and able to practice effective contraception from admission to 30 days after the final visit. Sexually active participants must use a combination of 2 of the following methods of contraception, including at least 1 so-called 'barrier' method: * Hormonal contraceptive (oral, transdermal patches, vaginal or injectable) * Intrauterine device with or without hormones * Condom ('barrier' method) * Diaphragm or cervical cap * Sexual abstinence * Have a body mass index 18 to 32 kilograms per square meter (kg/m²)
Exclusion criteria
* Are currently enrolled in a clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study * Have a history or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, convulsions, or any clinically significant laboratory abnormality * In the opinion of the investigator are considered to be a danger to themselves * Have an abnormality in the 12-lead electrocardiogram (ECG) * Have a history of clinically significant multiple or severe drug allergies or severe post treatment hypersensitivity reactions * Have donated blood of more than 500 milliliter (mL) within the previous month * Are unwilling to stop alcohol and caffeinated beverage consumption and smoking/use of tobacco while resident in the CRU * Have an average weekly alcohol intake that exceeds 21 units per week (1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits * Have an abnormal blood pressure * Participants with a history of drug abuse * Have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) * Are unwilling to comply with the required dietary restrictions
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 32 Days | An SAE is any AE from this 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 and important medical events that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent 1 of the other outcomes listed in the definition. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, are reported in the Adverse Events module section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | SAD: Day 1: predose, 1, 2, 4, 6, 8 and 12 hours postdose; Day 2 and Day 3: 24 and 48 hours postdose; 3-Period Food Effect Arms: Day 1: Predose, 1, 2, 4, 6, 8 and 12 hours, Day 2, Day 3 and Day 4: Predose, 24, 48 and 72 hours postdose | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC\[0-∞\]) of LY3526318 |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 24 Hours (AUC[0-24]) of LY3526318 | MAD: Day 1: Predose,1, 2, 4, 6, 8 and 12 hours post dose | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 24 hours (AUC\[0-24\]) of LY3526318 |
| PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | SAD: Day 1: predose, 1, 2, 4, 6, 8 and 12 hours postdose; Day 2 and Day 3: 24 and 48 hours postdose; 3-Period Food Effect Arms: Day 1: Predose, 1, 2, 4, 6, 8 and 12 hours, Day 2, Day 3 and Day 4: Predose, 24, 48 and 72 hours postdose | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 |
| PK: Time to Maximum Concentration (Tmax) of LY3526318 | SAD: Day 1: predose, 1, 2, 4, 6, 8 and 12 hours postdose; Day 2 and Day 3: 24 and 48 hours postdose; 3-Period Food Effect Arms: Day 1: Predose, 1, 2, 4, 6, 8 and 12 hours, Day 2, Day 3 and Day 4: Predose, 24, 48 and 72 hours postdose | PK: Time to Maximum Concentration (Tmax) of LY3526318 |
Countries
Netherlands
Participant flow
Pre-assignment details
This study consists of 2 parts: * Part A: Single-ascending dose (SAD, \[including a food effect (FE)\]). * Part B: Multiple-ascending dose (MAD). Both parts were randomized, double-blind, and placebo-controlled, with the exception of the 100 milligram (mg) FE part.
Participants by arm
| Arm | Count |
|---|---|
| SAD: Placebo Participants received placebo administered orally. | 12 |
| SAD: 10 mg LY3526318 Participants received 10 mg LY3526318 administered orally.. | 6 |
| SAD: 30 mg LY3526318 Participants received 30 mg LY3526318 administered orally. | 6 |
| SAD: 50 mg LY3526318 Participants received 50 mg LY3526318 administered orally. | 6 |
| SAD: 100 mg LY3526318 (Fasted) and 30 mg LY3526318 (Fed) Period 1:
Participants received 100 mg LY3526318 administered orally without a meal.
Period 2:
Participants received 30 mg LY3526318 administered orally with a meal. | 6 |
| SAD: 200 mg LY3526318 (Fasted) and 200 mg LY3526318 (Fed) Period 1:
Participants received 200 mg LY3526318 administered orally without a meal.
Period 2:
Participants received 200 mg LY3526318 administered orally with a meal. | 6 |
| SAD: 300 mg LY3526318 Participants received 300 mg LY3526318 administered orally. | 6 |
| SAD: 100 mg LY3526318 Fed Period 1: Participants received 100 mg LY3526318 administered orally 30 minutes after breakfast (Fed \[-30 min.\])
Period 2:
Participants received 100 mg LY3526318 orally 30 minutes before breakfast (Fed \[+30 min.\])
Period 3: Participants received 100 mg LY3526318 administered orally 60 minutes before breakfast (Fed \[+60 min.\]) | 3 |
| SAD: Placebo Fed Period 1: Participants received placebo administered orally 30 minutes after breakfast (Fed \[-30 min.\])
Period 2:
Participants received placebo administered orally 30 minutes before breakfast (Fed \[+30 min.\])
Period 3: Participants received placebo administered orally 60 minutes before breakfast (Fed \[+60 min.\]) | 1 |
| MAD: Placebo QD Participants received placebo one daily (QD) administered orally for 14 days. | 6 |
| MAD: 30 mg LY3526318 QD Participants received 30 mg LY3526318 QD administered orally for 14 days. | 6 |
| MAD: 60 mg LY3526318 QD Participants received 60 mg LY3526318 QD administered orally for 14 days. | 6 |
| MAD: 100 mg LY352631 QD Participants received 100 mg LY3526318 QD administered orally for 14 days | 6 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 2 | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | SAD: Placebo | Total | MAD: 100 mg LY352631 QD | MAD: 60 mg LY3526318 QD | MAD: 30 mg LY3526318 QD | MAD: Placebo QD | SAD: Placebo Fed | SAD: 100 mg LY3526318 Fed | SAD: 300 mg LY3526318 | SAD: 200 mg LY3526318 (Fasted) and 200 mg LY3526318 (Fed) | SAD: 100 mg LY3526318 (Fasted) and 30 mg LY3526318 (Fed) | SAD: 50 mg LY3526318 | SAD: 30 mg LY3526318 | SAD: 10 mg LY3526318 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 17 | 35.09 years STANDARD_DEVIATION 15.31 | 35 years STANDARD_DEVIATION 15 | 29 years STANDARD_DEVIATION 14 | 38 years STANDARD_DEVIATION 14 | 35 years STANDARD_DEVIATION 8 | 49 years | 46 years STANDARD_DEVIATION 21 | 40 years STANDARD_DEVIATION 19 | 39 years STANDARD_DEVIATION 14 | 36 years STANDARD_DEVIATION 20 | 26 years STANDARD_DEVIATION 3 | 30 years STANDARD_DEVIATION 17 | 41 years STANDARD_DEVIATION 20 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 6 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 70 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants | 1 Participants | 3 Participants | 6 Participants | 6 Participants | 4 Participants | 5 Participants | 5 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 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 6 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 | 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 |
| Race (NIH/OMB) White | 10 Participants | 60 Participants | 4 Participants | 5 Participants | 4 Participants | 3 Participants | 1 Participants | 2 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants |
| Region of Enrollment Netherlands | 12 Participants | 76 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 1 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 11 Participants | 70 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 1 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 3 Participants | 6 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 2 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 12 | 2 / 6 | 5 / 6 | 0 / 6 | 4 / 6 | 2 / 6 | 3 / 6 | 1 / 4 | 2 / 6 | 0 / 6 | 3 / 3 | 3 / 3 | 1 / 3 | 1 / 1 | 1 / 1 | 1 / 1 | 6 / 6 | 5 / 6 | 4 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 | 0 / 6 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 6 | 0 / 6 | 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 AE from this 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 and important medical events that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent 1 of the other outcomes listed in the definition. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, are reported in the Adverse Events module section.
Time frame: Baseline Up To 32 Days
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SAD: 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 |
| SAD: 10 mg LY3526318 | 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 |
| SAD: 30 mg LY3526318 | 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 |
| SAD: 50 mg LY3526318 | 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 |
| SAD: 100 mg LY3526318 (Fasted) and 30 mg LY3526318 (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 |
| SAD: 200 mg LY3526318 (Fasted) and 200 mg LY3526318 (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 |
| SAD: 300 mg LY3526318 | 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 |
| SAD: 100 mg LY3526318 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 |
| SAD: 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 |
| MAD: 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 |
| MAD: 30 mg LY3526318 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 |
| MAD: 60 mg LY3526318 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 |
| MAD: 100 mg LY352631 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): Area Under the Concentration Versus Time Curve From Zero to 24 Hours (AUC[0-24]) of LY3526318
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 24 hours (AUC\[0-24\]) of LY3526318
Time frame: MAD: Day 1: Predose,1, 2, 4, 6, 8 and 12 hours post dose
Population: MAD: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD: Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 24 Hours (AUC[0-24]) of LY3526318 | 6015 ng*h/mL | Geometric Coefficient of Variation 80.7 |
| SAD: 10 mg LY3526318 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 24 Hours (AUC[0-24]) of LY3526318 | 18525 ng*h/mL | Geometric Coefficient of Variation 48.1 |
| SAD: 30 mg LY3526318 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 24 Hours (AUC[0-24]) of LY3526318 | 25769 ng*h/mL | Geometric Coefficient of Variation 68.4 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC\[0-∞\]) of LY3526318
Time frame: SAD: Day 1: predose, 1, 2, 4, 6, 8 and 12 hours postdose; Day 2 and Day 3: 24 and 48 hours postdose; 3-Period Food Effect Arms: Day 1: Predose, 1, 2, 4, 6, 8 and 12 hours, Day 2, Day 3 and Day 4: Predose, 24, 48 and 72 hours postdose
Population: SAD: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD: Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 2322 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 64.3 |
| SAD: 10 mg LY3526318 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 6132 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 107 |
| SAD: 30 mg LY3526318 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 15442 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 63.6 |
| SAD: 50 mg LY3526318 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 55533 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 56.6 |
| SAD: 100 mg LY3526318 (Fasted) and 30 mg LY3526318 (Fed) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 45746 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 58.5 |
| SAD: 200 mg LY3526318 (Fasted) and 200 mg LY3526318 (Fed) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 58311 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 100.3 |
| SAD: 300 mg LY3526318 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | NA nanogram*hour per milliliter (ng*h/mL) | — |
| SAD: 100 mg LY3526318 Fed | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 10603 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 107 |
| SAD: Placebo Fed | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 6379 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 47.4 |
| MAD: Placebo QD | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 19028 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 15.3 |
| MAD: 30 mg LY3526318 QD | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of LY3526318 | 20237 nanogram*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 38.8 |
Secondary
PK: Maximum Observed Drug Concentration (Cmax) of LY3526318
PK: Maximum Observed Drug Concentration (Cmax) of LY3526318
Time frame: SAD: Day 1: predose, 1, 2, 4, 6, 8 and 12 hours postdose; Day 2 and Day 3: 24 and 48 hours postdose; 3-Period Food Effect Arms: Day 1: Predose, 1, 2, 4, 6, 8 and 12 hours, Day 2, Day 3 and Day 4: Predose, 24, 48 and 72 hours postdose
Population: SAD: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAD: Placebo | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 188 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 100.7 |
| SAD: 10 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 573 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 119.5 |
| SAD: 30 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 1321 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 58.9 |
| SAD: 50 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 4265 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 60.8 |
| SAD: 100 mg LY3526318 (Fasted) and 30 mg LY3526318 (Fed) | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 5047 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40.6 |
| SAD: 200 mg LY3526318 (Fasted) and 200 mg LY3526318 (Fed) | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 4879 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 120.8 |
| SAD: 300 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 204 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 51.6 |
| SAD: 100 mg LY3526318 Fed | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 719 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 139 |
| SAD: Placebo Fed | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 378 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 43.3 |
| MAD: Placebo QD | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 1288 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34.9 |
| MAD: 30 mg LY3526318 QD | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | 1407 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 91.2 |
Secondary
PK: Maximum Observed Drug Concentration (Cmax) of LY3526318
PK: Maximum Observed Drug Concentration (Cmax) of LY3526318
Time frame: MAD: Day 1 and Day 14: Predose, 1, 2, 4, 6, 8 and 12 hours post dose
Population: MAD: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAD: Placebo | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | Day 1 | 666 ng/mL | Geometric Coefficient of Variation 92.5 |
| SAD: Placebo | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | Day 14 | 1017 ng/mL | Geometric Coefficient of Variation 39.7 |
| SAD: 10 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | Day 1 | 2117 ng/mL | Geometric Coefficient of Variation 35.7 |
| SAD: 10 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | Day 14 | 2791 ng/mL | Geometric Coefficient of Variation 63.2 |
| SAD: 30 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | Day 1 | 2987 ng/mL | Geometric Coefficient of Variation 60.6 |
| SAD: 30 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | Day 14 | 4224 ng/mL | Geometric Coefficient of Variation 38.1 |
Secondary
PK: Time to Maximum Concentration (Tmax) of LY3526318
PK: Time to Maximum Concentration (Tmax) of LY3526318
Time frame: SAD: Day 1: predose, 1, 2, 4, 6, 8 and 12 hours postdose; Day 2 and Day 3: 24 and 48 hours postdose; 3-Period Food Effect Arms: Day 1: Predose, 1, 2, 4, 6, 8 and 12 hours, Day 2, Day 3 and Day 4: Predose, 24, 48 and 72 hours postdose
Population: SAD: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SAD: Placebo | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 2.03 hours |
| SAD: 10 mg LY3526318 | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 2.00 hours |
| SAD: 30 mg LY3526318 | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 3.00 hours |
| SAD: 50 mg LY3526318 | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 4.00 hours |
| SAD: 100 mg LY3526318 (Fasted) and 30 mg LY3526318 (Fed) | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 4.00 hours |
| SAD: 200 mg LY3526318 (Fasted) and 200 mg LY3526318 (Fed) | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 4.00 hours |
| SAD: 300 mg LY3526318 | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 12.00 hours |
| SAD: 100 mg LY3526318 Fed | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 4.00 hours |
| SAD: Placebo Fed | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 4.03 hours |
| MAD: Placebo QD | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 4.00 hours |
| MAD: 30 mg LY3526318 QD | PK: Time to Maximum Concentration (Tmax) of LY3526318 | 4.00 hours |
Secondary
PK: Time to Maximum Concentration (Tmax) of LY3526318
PK: Time to Maximum Concentration (Tmax) of LY3526318
Time frame: MAD: Day 1 and Day 14: Predose, 1, 2, 4, 6, 8 and 12 hours post dose
Population: MAD: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| SAD: Placebo | PK: Time to Maximum Concentration (Tmax) of LY3526318 | Day 1 | 4.00 hours |
| SAD: Placebo | PK: Time to Maximum Concentration (Tmax) of LY3526318 | Day 14 | 4.01 hours |
| SAD: 10 mg LY3526318 | PK: Time to Maximum Concentration (Tmax) of LY3526318 | Day 1 | 3.00 hours |
| SAD: 10 mg LY3526318 | PK: Time to Maximum Concentration (Tmax) of LY3526318 | Day 14 | 4.01 hours |
| SAD: 30 mg LY3526318 | PK: Time to Maximum Concentration (Tmax) of LY3526318 | Day 1 | 3.00 hours |
| SAD: 30 mg LY3526318 | PK: Time to Maximum Concentration (Tmax) of LY3526318 | Day 14 | 4.00 hours |