Healthy
Conditions
Brief summary
The study has two parts. In Part A, single increasing doses of LY3451838 will be administered intravenously (into a vein). In Part B, a single dose of LY3451838 will be administered subcutaneously (just under the skin).
Interventions
DRUGLY3451838
Administered IV Part A
DRUGPlacebo
Administered IV in Part A and SC in Part B
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
* Male participants must adhere to contraception restrictions * Female participants must be of non-childbearing potential due to: * Menopause: spontaneous amenorrhea for at least 12 months not induced by a medical condition such as anorexia nervosa and not taking medications that induced the amenorrhea (e.g., oral contraceptives, hormones, gonadotropin releasing hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy) * Surgical sterilization * Have a body mass index of 18 to 35 kilograms per square meter (kg/m²) * Have clinical laboratory test results within normal reference range or with acceptable deviations * Have an estimated glomerular filtration rate greater than or equal to (≥) 60 milliliters per minute per 1.73 meters squared (mL/minute/1.73 m²) of body surface area * Have venous access sufficient to allow for blood sampling
Exclusion criteria
* Are currently enrolled in or discontinued from a clinical trial within the last 30 days, or have previously completed or withdrawn from this study * Have a history or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, renal, endocrine, psychiatric or neurological disease, or any clinically significant laboratory abnormality * Have history of or presence of uncontrolled asthma, significant atopy, or significant rheumatological or autoimmune diseases * Have had lymphoma, leukemia, or any malignancy within the past 5 years, or breast cancer within the past 10 years (with some exceptions) * Have used, or intend to use some prescription or over the counter medications, including herbal medications within 14 days prior to dosing * Have an abnormality in the 12-lead electrocardiogram (ECG) or Fridericia's corrected QT (QTcF) * Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies, hepatitis C and/or positive hepatitis C antibody, or hepatitis B and/or positive hepatitis B surface antigen * Have donated blood of more than 450 milliliters (mL) within the last 3 months * Are unwilling to stop alcohol consumption while resident in the Clinical Research Unit (CRU) * Have an average weekly alcohol intake that exceeds 21 units per week for males and 14 units per week for females (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) * Current smoker of more than 10 cigarettes or equivalent per day and unable to stop smoking while in the CRU * Have an abnormal blood pressure * Have clinically significant proteinuria or hematuria * Positive findings for known drugs of abuse * Have received treatment with biologic agents within 3 months or 5 half-lives (whichever is longer) * Have clinically significant allergies, or intolerance to corticosteroids, or severe post treatment hypersensitivity reactions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Treatment Emergent Adverse Event | Baseline through 20 Weeks | A summary of other non-serious Adverse Events (AE's), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section. |
| Number of Participants With One or More Serious Adverse Events | Baseline through 20 Weeks | A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838 | Part A: Predose, End of Infusion, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose; Part B: Predose, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose | PK: AUC of LY3451838 |
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838 | Part A: Predose, End of Infusion, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose; Part B: Predose, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose | PK: Cmax of LY3451838 |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 25 Milligram (mg) LY3451838 Part A 25 mg LY3451838 single dose administered intravenously (IV) | 5 |
| 75 mg LY3451838 Part A 75 mg LY3451838 single dose administered IV. | 6 |
| 250 mg LY3451838 Part A 250 mg LY3451838 single dose administered IV. | 5 |
| 500 mg LY3451838 Part A 500 mg LY3451838 single dose administered IV. | 6 |
| 1000 mg LY3451838 Part A 1000 mg LY3451838 single dose administered IV. | 5 |
| 1500 mg LY3451838 Part A 1500 mg LY3451838 single dose administered IV. | 6 |
| 250 mg LY3451838 Part B 250 mg LY3451838 single dose administered subcutaneously (SC). | 6 |
| Placebo Placebo matching single dose administered IV in Part A and administered SC in Part B. | 14 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 25 Milligram (mg) LY3451838 Part A | Total | Placebo | 250 mg LY3451838 Part B | 1500 mg LY3451838 Part A | 1000 mg LY3451838 Part A | 500 mg LY3451838 Part A | 250 mg LY3451838 Part A | 75 mg LY3451838 Part A |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.6 years STANDARD_DEVIATION 10.1 | 42.8 years STANDARD_DEVIATION 11.4 | 40.5 years STANDARD_DEVIATION 11 | 49.8 years STANDARD_DEVIATION 6 | 43.3 years STANDARD_DEVIATION 11.3 | 38.4 years STANDARD_DEVIATION 9.6 | 40.2 years STANDARD_DEVIATION 15 | 41.4 years STANDARD_DEVIATION 14.1 | 44.0 years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 52 Participants | 14 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 5 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 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 53 Participants | 14 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 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 | 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 |
| 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 |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Singapore | 5 Participants | 53 Participants | 14 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 8 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 45 Participants | 12 Participants | 4 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 4 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 14 |
| other Total, other adverse events | 4 / 5 | 5 / 6 | 4 / 5 | 6 / 6 | 4 / 5 | 5 / 6 | 4 / 6 | 12 / 14 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 14 |
Outcome results
Primary
Number of Participants With Any Treatment Emergent Adverse Event
A summary of other non-serious Adverse Events (AE's), and all Serious Adverse Events (SAE's), regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through 20 Weeks
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 25 Milligram (mg) LY3451838 Part A | Number of Participants With Any Treatment Emergent Adverse Event | 4 Participants |
| 75 mg LY3451838 Part A | Number of Participants With Any Treatment Emergent Adverse Event | 5 Participants |
| 250 mg LY3451838 Part A | Number of Participants With Any Treatment Emergent Adverse Event | 4 Participants |
| 500 mg LY3451838 Part A | Number of Participants With Any Treatment Emergent Adverse Event | 6 Participants |
| 1000 mg LY3451838 Part A | Number of Participants With Any Treatment Emergent Adverse Event | 4 Participants |
| 1500 mg LY3451838 Part A | Number of Participants With Any Treatment Emergent Adverse Event | 5 Participants |
| 250 mg LY3451838 Part B | Number of Participants With Any Treatment Emergent Adverse Event | 4 Participants |
| Placebo | Number of Participants With Any Treatment Emergent Adverse Event | 12 Participants |
Primary
Number of Participants With One or More Serious Adverse Events
A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline through 20 Weeks
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 25 Milligram (mg) LY3451838 Part A | Number of Participants With One or More Serious Adverse Events | 0 Participants |
| 75 mg LY3451838 Part A | Number of Participants With One or More Serious Adverse Events | 0 Participants |
| 250 mg LY3451838 Part A | Number of Participants With One or More Serious Adverse Events | 0 Participants |
| 500 mg LY3451838 Part A | Number of Participants With One or More Serious Adverse Events | 0 Participants |
| 1000 mg LY3451838 Part A | Number of Participants With One or More Serious Adverse Events | 0 Participants |
| 1500 mg LY3451838 Part A | Number of Participants With One or More Serious Adverse Events | 0 Participants |
| 250 mg LY3451838 Part B | Number of Participants With One or More Serious Adverse Events | 0 Participants |
| Placebo | Number of Participants With One or More Serious Adverse Events | 0 Participants |
Secondary
Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838
PK: AUC of LY3451838
Time frame: Part A: Predose, End of Infusion, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose; Part B: Predose, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 25 Milligram (mg) LY3451838 Part A | Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838 | 1580 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 25 |
| 75 mg LY3451838 Part A | Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838 | 7510 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 24.4 |
| 250 mg LY3451838 Part A | Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838 | 21900 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 25 |
| 500 mg LY3451838 Part A | Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838 | 46100 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 15.4 |
| 1000 mg LY3451838 Part A | Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838 | 85500 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 19.6 |
| 1500 mg LY3451838 Part A | Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838 | 128000 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 12.2 |
| 250 mg LY3451838 Part B | Pharmacokinetics (PK): Area Under the Serum Concentration-Time Curve From 0 to Infinity (AUC 0 -∞) of LY3451838 | 2040 microgram*hour per milliliter (μg*h/mL) | Geometric Coefficient of Variation 57 |
Secondary
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838
PK: Cmax of LY3451838
Time frame: Part A: Predose, End of Infusion, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose; Part B: Predose, 3, 6, 12, 24, 36, 48 h, and Days 5, 7, 9, 15, 22, 29, 43, 57, 71, 85, and 141 post-dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 25 Milligram (mg) LY3451838 Part A | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838 | 8.54 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 39.1 |
| 75 mg LY3451838 Part A | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838 | 30.9 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 13.4 |
| 250 mg LY3451838 Part A | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838 | 89.1 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 15.8 |
| 500 mg LY3451838 Part A | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838 | 172 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 27.1 |
| 1000 mg LY3451838 Part A | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838 | 318 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 24.1 |
| 1500 mg LY3451838 Part A | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838 | 523 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 22.4 |
| 250 mg LY3451838 Part B | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3451838 | 1.97 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 113.7 |