Healthy
Conditions
Brief summary
The main purpose of this study in healthy participants is to learn more about the safety of LY3493269 and any side effects that might be associated with it. Blood tests will be performed to check how much LY3493269 gets into the bloodstream and how long it takes the body to eliminate it. For each participant, the study will last about 10 weeks and may include 12 visits, including five nights in a row in the clinical research center.
Interventions
DRUGLY3493269
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
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are male or female not of childbearing potential * Body mass index within the range of 19.0 to 40.0 kilograms per square meter (kg/m²) (inclusive) * Participants who are healthy as determined through medical evaluation including screening medical history, physical examination, vital signs, clinical laboratory tests, and electrocardiogram (ECG) * Have clinical laboratory test results within normal reference range for the population or clinical research unit (CRU), or results with acceptable deviations that are judged to be not clinically significant by the investigator * Have glycated hemoglobin level of less than (\<)6.5 percent (%)
Exclusion criteria
* Have a supine heart rate (HR) less than 50 beats per minute (bpm) or greater than 100 bpm. If a repeat measurement shows values within the range, the participant can be included in the trial * Have a mean supine systolic blood pressure (BP) higher than 160 millimeters of Mercury (mmHg) and a mean supine diastolic BP higher than 95 mmHg from 2 assessments at screening (excluding white-coat hypertension); therefore, if a repeated measurement shows values within the range, the participant can be included in the trial * Have undergone any form of bariatric surgery * Have a history of gastrointestinal (GI) bleeding or duodenal ulcers * Have a personal or family history of medullary thyroid carcinoma or have multiple endocrine neoplasia syndrome type 2 * Have a history of acute or chronic pancreatitis, or elevation in serum lipase and/or amylase levels greater than 1.5 times the upper limit of normal (ULN) * Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis * Have been treated with prescription drugs that promote weight loss within 3 months prior to screening * Have participated within the past 30 days of screening in a clinical study involving an investigational product (IP); at least 5 half-lives or 30 days, whichever is longer, should have passed * Have an abnormality in the 12-lead 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, such as a QT interval corrected using Fridericia's formula (QTcF) greater than (\>)450 milliseconds (msec) for males and \>470 msec for females, short PR interval (\<120 msec), or PR interval \>220 msec, second and third atrioventricular block, intraventricular conduction delay with QRS \>120 msec, right bundle branch block, left bundle branch block or Wolff-Parkinson-White syndrome * Have serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times (X) ULN or total bilirubin level (TBL) \>1.5X ULN * Have known allergies to LY3493269, related compounds, or any components of the formulation (including C10), or a history of significant atopy
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 through Day 43 | An SAE is an adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. A summary of SAEs and other non-serious adverse events (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 LY3493269 From Day 1 and Day 3 Doses | Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 2. 6, 8, 12 and Day 2 predose; Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose, Day 4, pre-dose | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269. Note: 1. 24 hour timepoint for Day 1 is the Day 2 pre-dose timepoint, which is the reason why Day 2 pre-dose is included in the timeframe. 2. 24 hour timepoint for Day 3 is the Day 4 pre-dose timepoint, which is the reason why Day 4 pre-dose is included in the timeframe. |
| PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and Day 2 predose; Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose, Day 4, pre-dose | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC\[0-24\]) of LY3493269 From Day 1 and Day 3 Doses Note: 1. 24 hour timepoint for Day 1 is the Day 2 pre-dose timepoint, which is the reason why Day 2 pre-dose is included in the timeframe. 2. 24 hour timepoint for Day 3 is the Day 4 pre-dose timepoint, which is the reason why Day 4 pre-dose is included in the timeframe. |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo once daily (QD) administered orally over 3 consecutive study days. | 8 |
| Cohort 1: 8 mg LY3493269 + 500 mg C10 Participants received 8 milligrams (mg) LY3493269 + 500 mg permeation enhancer sodium caprate(C10) QD administered orally over 3 consecutive study days. | 8 |
| Cohort 2: 24 mg LY3493269 + 500 mg C10 Participants received 24 mg LY3493269 + 500 mg C10 QD administered orally over 3 consecutive study days. | 8 |
| Cohort 3: 48 mg LY3493269 + 500 mg C10 Participants received 48 mg LY3493269 + 500 mg C10 QD administered orally over 3 consecutive study days. | 8 |
| Cohort 4: 24 mg LY3493269 + 250 mg C10 Participants received 24 mg LY3493269 + 250 mg C10 QD administered orally over 3 consecutive study days. | 8 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1: 8 mg LY3493269 + 500 mg C10 | Cohort 2: 24 mg LY3493269 + 500 mg C10 | Cohort 3: 48 mg LY3493269 + 500 mg C10 | Placebo | Cohort 4: 24 mg LY3493269 + 250 mg C10 |
|---|---|---|---|---|---|---|
| Age, Continuous | 43.9 years STANDARD_DEVIATION 8.6 | 44.9 years STANDARD_DEVIATION 8.4 | 44.8 years STANDARD_DEVIATION 9.1 | 44.9 years STANDARD_DEVIATION 11.7 | 41.3 years STANDARD_DEVIATION 6.6 | 43.9 years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 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 |
| Race (NIH/OMB) Asian | 40 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Singapore | 40 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 7 / 8 | 7 / 8 | 8 / 8 | 7 / 8 | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
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 an adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.
Time frame: Baseline through Day 43
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 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 |
| 8 mg LY3493269 + 500 mg C10 | 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 |
| 24 mg LY3493269 + 500 mg C10 | 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 |
| 48 mg LY3493269 + 500 mg C10 | 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 |
| 24 mg LY3493269 + 250 mg C10 | 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 LY3493269 From Day 1 and Day 3 Doses
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269. Note: 1. 24 hour timepoint for Day 1 is the Day 2 pre-dose timepoint, which is the reason why Day 2 pre-dose is included in the timeframe. 2. 24 hour timepoint for Day 3 is the Day 4 pre-dose timepoint, which is the reason why Day 4 pre-dose is included in the timeframe.
Time frame: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 2. 6, 8, 12 and Day 2 predose; Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose, Day 4, pre-dose
Population: All randomized participants received at least 1 full dose of LY3493269 and had evaluable PK sample. Participants may have been excluded from the PK summary statistics and statistical analysis if they had an adverse event of vomiting that occurred at or before 2 times median time to maximum observed drug Concentration (tmax)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses | Day 1 | 11.7 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 176 |
| Placebo | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses | Day 3 | 17.7 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 149 |
| 8 mg LY3493269 + 500 mg C10 | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses | Day 3 | 49.1 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 449 |
| 8 mg LY3493269 + 500 mg C10 | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses | Day 1 | 39.9 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 248 |
| 24 mg LY3493269 + 500 mg C10 | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses | Day 1 | 80.8 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 359 |
| 24 mg LY3493269 + 500 mg C10 | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses | Day 3 | 41.9 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 157 |
| 48 mg LY3493269 + 500 mg C10 | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses | Day 1 | 68.2 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 97 |
| 48 mg LY3493269 + 500 mg C10 | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of LY3493269 From Day 1 and Day 3 Doses | Day 3 | 69.4 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 263 |
Secondary
PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses
PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC\[0-24\]) of LY3493269 From Day 1 and Day 3 Doses Note: 1. 24 hour timepoint for Day 1 is the Day 2 pre-dose timepoint, which is the reason why Day 2 pre-dose is included in the timeframe. 2. 24 hour timepoint for Day 3 is the Day 4 pre-dose timepoint, which is the reason why Day 4 pre-dose is included in the timeframe.
Time frame: Day 1: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and Day 2 predose; Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 hours post dose, Day 4, pre-dose
Population: All randomized participants received at least 1 full dose of LY3493269 and had evaluable PK sample. Participants may have been excluded from the PK summary statistics and statistical analysis if they had an adverse event of vomiting that occurred at or before 2 times median time to maximum observed drug Concentration (tmax).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 1 | 170 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 185 |
| Placebo | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 3 | 302 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 139 |
| 8 mg LY3493269 + 500 mg C10 | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 3 | 868 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 381 |
| 8 mg LY3493269 + 500 mg C10 | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 1 | 601 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 310 |
| 24 mg LY3493269 + 500 mg C10 | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 1 | 1180 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 381 |
| 24 mg LY3493269 + 500 mg C10 | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 3 | 746 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 156 |
| 48 mg LY3493269 + 500 mg C10 | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 1 | 1080 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 104 |
| 48 mg LY3493269 + 500 mg C10 | PK: Area Under the Concentration Versus Time Curve From Zero to 24 (AUC[0-24]) of LY3493269 From Day 1 and Day 3 Doses | Day 3 | 1340 Nanograms hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 276 |