Healthy
Conditions
Brief summary
The main purpose of this study is to conduct blood tests to measure how much LY3493269 is in the bloodstream and how the body handles and eliminates LY3493269 when administered orally as test compared to reference formulations in healthy participants in fed and/or fasted states. The study will also evaluate the safety and tolerability of LY3493269 in these participants. The study will last up to 43 days excluding the screening period.
Interventions
DRUGLY3493269
Administered orally.
DRUGSodium Caprate (C10)
Administered orally.
DRUGSalcaprozate Sodium (SNAC)
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female participants who are overtly healthy as determined by medical evaluation * Participants with body mass index (BMI) of 19.0 to 40.0 kilograms per meter squared (kg/m²) * Males who agree to use highly effective/effective methods of contraception and only women not of childbearing potential may participate in the trial
Exclusion criteria
* Have a history of atopy (severe or multiple allergic manifestations) or clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, anaphylaxis, angioedema, or exfoliative dermatitis) * Have a significant history of or current cardiovascular (for example, myocardial infarction, congestive heart failure, cerebrovascular accident, venous thromboembolism, etc.), respiratory, renal, gastrointestinal (GI) including involving the liver, gallbladder or gallbladder surgery, 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 investigational product (IP); or of interfering with the interpretation of data. * Have a mean supine heart rate (HR) less than 45 bpm or greater than 100 bpm from 2 assessments at screening. * Have a mean supine systolic blood pressure (BP) higher than 160 mmHg and a mean supine diastolic BP higher than 95 mmHg from 2 assessments at screening * Have undergone any form of bariatric surgery. * Have a history of GI bleeding, or gastric or duodenal ulcers. * Have a personal or family history of medullary thyroid carcinoma or 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 clinical signs or symptoms of liver disease, acute or chronic hepatitis. * Have evidence of significant active neuropsychiatric disease as determined by the investigator. * Have been treated with prescription drugs that promote weight loss within 3 months prior to screening. * 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. * Have participated within the past 30 days of screening in a clinical study involving an IP; at least 5 half-lives or 30 days, whichever is longer, should have passed. * Have an abnormality in the 12-lead electrocardiogram (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) \>450 msec for males and \>470 msec for females, short PR interval (\<120 msec), or PR interval \>220 msec, second- or third-degree 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) \>1.5x ULN or total bilirubin level (TBL) \>1.5x ULN. * Show evidence of human immunodeficiency virus infection and/or positive human immunodeficiency virus antibodies. * Show evidence of hepatitis C and/or positive hepatitis C antibody. * Show evidence of hepatitis B, positive hepatitis B core antibody, and/or positive hepatitis B surface antigen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC [0-∞]) of LY3493269 | Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14, 24, 48, 72,120, 288, 624 and 960 hours (h) post-dose | PK: AUC (0-∞) of LY3493269 |
| Part A: PK: Area Under the Concentration Versus Time Curve During One Dosing Interval (AUCτ) of LY3493269 | Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14 and 24 hours (h) post-dose | PK: AUCτ of LY3493269 |
| Part A: PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14 and 24 hours (h) post-dose | Cmax of LY3493269 |
Countries
Singapore
Participant flow
Pre-assignment details
The study was planned to be conducted in two parts (Part A and Part B) - * After the completion of Part A, following a preplanned review of the safety and pharmacokinetic data from Part A, it was determined that sufficient data had been obtained. Hence, the decision was made not to proceed with Part B, and the study was terminated early. * Only Part A results data are reported below.
Participants by arm
| Arm | Count |
|---|---|
| Part A: 4 mg LY3493269 Test Capsule 1 + 280 mg C10 (Fasted) * Participants were administered oral doses of 4 mg LY3493269 test capsule formulation 1, co-administered with 280 mg of C10.
* This regimen was administered once daily on Days 1, 2, and 3, following an overnight fast. | 11 |
| Part A: 4 mg LY3493269 Test Capsule 2 + 280 mg C10 (Fasted) * Participants were administered oral doses of 4 mg LY3493269 test capsule formulation 2, co-administered with 280 mg of C10.
* This regimen was administered once daily on Days 1, 2, and 3, following an overnight fast. | 15 |
| Part A: 4 mg LY3493269 Reference Tablet + 300 mg SNAC (Fasted) * Participants were administered oral doses of 4 mg LY3493269 reference tablet formulation, co-administered with 300 mg of SNAC.
* This regimen was administered once daily on Days 1, 2, and 3, following an overnight fast. | 14 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Part A: 4 mg LY3493269 Test Capsule 1 + 280 mg C10 (Fasted) | Part A: 4 mg LY3493269 Test Capsule 2 + 280 mg C10 (Fasted) | Part A: 4 mg LY3493269 Reference Tablet + 300 mg SNAC (Fasted) |
|---|---|---|---|---|
| Age, Continuous | 41.6 years STANDARD_DEVIATION 10.6 | 42.9 years STANDARD_DEVIATION 11.8 | 42.8 years STANDARD_DEVIATION 10.4 | 39.4 years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 Participants | 11 Participants | 15 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 39 Participants | 11 Participants | 15 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Singapore | 40 Participants | 11 Participants | 15 Participants | 14 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 38 Participants | 11 Participants | 14 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 9 / 11 | 11 / 15 | 11 / 14 |
| serious Total, serious adverse events | 1 / 11 | 0 / 15 | 0 / 14 |
Outcome results
Primary
Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC [0-∞]) of LY3493269
PK: AUC (0-∞) of LY3493269
Time frame: Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14, 24, 48, 72,120, 288, 624 and 960 hours (h) 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 |
|---|---|---|---|
| Part A: 4 mg LY3493269 Test Capsule 1 + 280 mg C10 (Fasted) | Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC [0-∞]) of LY3493269 | 1590 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 100 |
| Part A: 4 mg LY3493269 Test Capsule 2 + 280 mg C10 (Fasted) | Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC [0-∞]) of LY3493269 | 4880 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 58 |
| Part A: 4 mg LY3493269 Reference Tablet + 300 mg SNAC (Fasted) | Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC [0-∞]) of LY3493269 | 12200 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 112 |
Comparison: AUC (0-∞) was log-transformed and analyzed via mixed model for repeated measures with fixed effects for treatment, profile day and the treatment-by-day interaction, and a random effect for participant. The least square means (LSMs) and differences in LSMs were back transformed to produce the ratio between geometric least square means (GLSMs).90% CI: [0.0741, 0.228]Mixed Models Analysis
Comparison: AUC (0-∞) was log-transformed and analyzed via mixed model for repeated measures with fixed effects for treatment, profile day and the treatment-by-day interaction, and a random effect for participant. The LSMs and differences in LSMs were back transformed to produce the ratio between GLSMs.90% CI: [0.237, 0.669]Mixed Models Analysis
Primary
Part A: PK: Area Under the Concentration Versus Time Curve During One Dosing Interval (AUCτ) of LY3493269
PK: AUCτ of LY3493269
Time frame: Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14 and 24 hours (h) 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 |
|---|---|---|---|
| Part A: 4 mg LY3493269 Test Capsule 1 + 280 mg C10 (Fasted) | Part A: PK: Area Under the Concentration Versus Time Curve During One Dosing Interval (AUCτ) of LY3493269 | 150 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 69 |
| Part A: 4 mg LY3493269 Test Capsule 2 + 280 mg C10 (Fasted) | Part A: PK: Area Under the Concentration Versus Time Curve During One Dosing Interval (AUCτ) of LY3493269 | 402 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 66 |
| Part A: 4 mg LY3493269 Reference Tablet + 300 mg SNAC (Fasted) | Part A: PK: Area Under the Concentration Versus Time Curve During One Dosing Interval (AUCτ) of LY3493269 | 1220 nanograms*hours per milliliter(ng*h/mL) | Geometric Coefficient of Variation 108 |
Primary
Part A: PK: Maximum Observed Drug Concentration (Cmax) of LY3493269
Cmax of LY3493269
Time frame: Day 3: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 9, 10, 12, 14 and 24 hours (h) 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 |
|---|---|---|---|
| Part A: 4 mg LY3493269 Test Capsule 1 + 280 mg C10 (Fasted) | Part A: PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | 7.49 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 80 |
| Part A: 4 mg LY3493269 Test Capsule 2 + 280 mg C10 (Fasted) | Part A: PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | 25.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 73 |
| Part A: 4 mg LY3493269 Reference Tablet + 300 mg SNAC (Fasted) | Part A: PK: Maximum Observed Drug Concentration (Cmax) of LY3493269 | 70.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 108 |
Comparison: Cmax was log-transformed and analyzed via mixed model for repeated measures with fixed effects for treatment, profile day and the treatment-by-day interaction, and a random effect for participant. The LSMs and differences in LSMs were back transformed to produce the ratio between GLSMs.90% CI: [0.062, 0.182]Mixed Models Analysis
Comparison: Cmax was log-transformed and analyzed via mixed model for repeated measures with fixed effects for treatment, profile day and the treatment-by-day interaction, and a random effect for participant. The LSMs and differences in LSMs were back transformed to produce the ratio between GLSMs.90% CI: [0.206, 0.569]Mixed Models Analysis