Healthy
Conditions
Brief summary
The main purpose of this study is to evaluate the safety and tolerability of LY3493269 in healthy participants. The blood tests will be performed to check how much LY3493269 gets into the bloodstream, how long the body takes to eliminate it and how body handles LY3493269. The study will last up to approximately 71 days for each participant, including screening
Interventions
DRUGLY3493269
Administered orally.
DRUGPlacebo
Administered orally.
DRUGSalcaprozate Sodium
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Are male or female not of childbearing potential 2. Body mass index within the range of 19.0 to 40.0 kilograms per square meter (kg/m²) (inclusive) 3. Participants who are healthy as determined through medical evaluation including screening medical history, physical examination, vital signs, clinical laboratory tests, and electrocardiogram (ECG) 4. 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 5. Have venous access sufficient to allow blood sampling as per the protocol.
Exclusion criteria
1. Have a significant history of or current CV (for example, myocardial infarction, congestive heart failure, cerebrovascular accident, venous thromboembolism, etc.), respiratory, renal, GI, endocrine, hematological (including history of thrombocytopenia), or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk while taking the IP; or of interfering with the interpretation of data 2. Have undergone any form of bariatric surgery 3. Have a history of gastrointestinal (GI) bleeding or duodenal ulcers 4. Have a personal or family history of medullary thyroid carcinoma or have multiple endocrine neoplasia syndrome type 2 5. 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) 6. Have clinical signs or symptoms of liver disease, acute or chronic hepatitis 7. Have evidence of significant active neuropsychiatric disease as determined by the investigator 8. Have been treated with prescription drugs that promote weight loss within 3 months prior to screening 9. Are currently enrolled in a clinical study involving an IP or any other type of medical research judged not to be scientifically or medically compatible with this study 10. 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 11. 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 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 12. Have serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times (X) ULN or total bilirubin level (TBL) \>1.5X ULN 13. Show evidence of HIV infection and/or positive human HIV antibodies 14. Show evidence of hepatitis C and/or positive hepatitis C antibody 15. Show evidence of hepatitis B, positive hepatitis B core antibody, and/or positive hepatitis B surface antigen 16. Have donated blood of more than 450 mL, or have participated in a clinical study that required similar blood volume drawn within the past 3 calendar months 17. Have known allergies to LY3493269, related compounds, or any components of the formulation (including SNAC), or a history of significant atopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) | Baseline through Day 44 | TEAE is an untoward medical occurrence that emerges during a defined treatment period, having been absent pretreatment, or worsens relative to the pretreatment state, and does not necessarily have to have a causal relationship with this treatment. A summary of serious adverse events (SAEs), TEAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Adverse Events section of this record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC [0-24]) of LY3493269 | Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, & 24 hours post dose | PK: AUC (0-24) of LY3493269 |
| PK: Maximum Concentration (Cmax) of LY3493269 | Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, & 24 hours post dose | PK: Cmax of LY3493269 |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo orally QD for three consecutive days. | 8 |
| 8 mg LY3493269 + 600 mg SNAC Participants received 8 mg LY3493269 and 600 mg SNAC QD administered orally for three consecutive days. | 8 |
| 24 mg LY3493269 + 600 mg SNAC Participants received 24 mg LY3493269 and 600 mg SNAC QD administered orally for three consecutive days. | 8 |
| 12 mg LY3493269 + 300 mg SNAC Participants received 12 mg LY3493269 and 300 mg SNAC QD administered orally for three consecutive days. | 8 |
| 4 mg LY3493269 + 300 mg SNAC Participants received 4 mg LY3493269 and 300 mg SNAC QD administered orally for three consecutive days. | 8 |
| Total | 40 |
Baseline characteristics
| Characteristic | Placebo | 8 mg LY3493269 + 600 mg SNAC | 24 mg LY3493269 + 600 mg SNAC | 12 mg LY3493269 + 300 mg SNAC | 4 mg LY3493269 + 300 mg SNAC | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 44.9 Years STANDARD_DEVIATION 8.7 | 39.1 Years STANDARD_DEVIATION 9.9 | 45.5 Years STANDARD_DEVIATION 10.3 | 44.4 Years STANDARD_DEVIATION 6.7 | 45.9 Years STANDARD_DEVIATION 7 | 44.0 Years STANDARD_DEVIATION 8.6 |
| 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 | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 40 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 | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 40 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 | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 40 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 7 Participants | 8 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 4 / 8 | 8 / 8 | 8 / 8 | 7 / 8 | 6 / 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 Treatment-Emergent Adverse Event(s) (TEAEs)
TEAE is an untoward medical occurrence that emerges during a defined treatment period, having been absent pretreatment, or worsens relative to the pretreatment state, and does not necessarily have to have a causal relationship with this treatment. A summary of serious adverse events (SAEs), TEAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Adverse Events section of this record.
Time frame: Baseline through Day 44
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) | 4 Participants |
| 8 mg LY3493269 + 600 mg SNAC | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) | 8 Participants |
| 24 mg LY3493269 + 600 mg SNAC | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) | 8 Participants |
| 12 mg LY3493269 + 300 mg SNAC | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) | 7 Participants |
| 4 mg LY3493269 + 300 mg SNAC | Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) | 6 Participants |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC [0-24]) of LY3493269
PK: AUC (0-24) of LY3493269
Time frame: Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, & 24 hours post dose
Population: All enrolled participants who received at least one dose of LY3493269 and had at least one evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC [0-24]) of LY3493269 | 2960 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 137 |
| 8 mg LY3493269 + 600 mg SNAC | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC [0-24]) of LY3493269 | 9680 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 46 |
| 24 mg LY3493269 + 600 mg SNAC | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC [0-24]) of LY3493269 | 4850 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 146 |
| 12 mg LY3493269 + 300 mg SNAC | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours (AUC [0-24]) of LY3493269 | 1150 nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 77 |
Secondary
PK: Maximum Concentration (Cmax) of LY3493269
PK: Cmax of LY3493269
Time frame: Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, & 24 hours post dose
Population: All enrolled participants who received at least one dose of LY3493269 and had at least one evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | PK: Maximum Concentration (Cmax) of LY3493269 | 166 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 137 |
| 8 mg LY3493269 + 600 mg SNAC | PK: Maximum Concentration (Cmax) of LY3493269 | 527 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
| 24 mg LY3493269 + 600 mg SNAC | PK: Maximum Concentration (Cmax) of LY3493269 | 270 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 122 |
| 12 mg LY3493269 + 300 mg SNAC | PK: Maximum Concentration (Cmax) of LY3493269 | 62.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 84 |