Atopic Dermatitis, Healthy
Conditions
Brief summary
The main purpose of this study is to evaluate the safety and tolerability of LY3872386 in healthy participants and participants with atopic dermatitis. The safety of prednisone is also evaluated in healthy participants. Blood tests will be performed to investigate how the body processes the LY3872386 following single and multiple dosing in healthy participants and participants with atopic dermatitis. Blood tests will also be performed to investigate how the body processes the prednisone in healthy participants. The study is conducted in three parts (part A, B and C). The study will last up to approximately 85, 183 and 44 days for parts A, B, and C, respectively.
Interventions
DRUGLY3872386
Administered IV.
DRUGPrednisone
Administered orally.
DRUGPlacebo
Administered IV.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Part A, B are double blind and part C is open-label.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
Part A and C: * Overtly healthy as determined by medical evaluation 1. To qualify as Japanese for the purpose of this study, the participant must be first generation Japanese, defined as the participant's biological parents and all of the participant's biological grandparents must be of exclusive Japanese descent, and must have been born in Japan 2. To qualify as Chinese for the purpose of this study, the participant must be, at a minimum, third-generation Chinese, defined as all 4 of the participant's biological grandparents must be of exclusive Chinese descent and born in China * Have a body mass index of 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive * Male participants who agree to use highly effective or effective methods of contraception and women not of childbearing potential may participate in part A and C Part B: * Participants who have a diagnosis of atopic dermatitis at least 12 months prior to screening as defined by the American Academy of Dermatology * Have a history, documented by a physician and/or investigator, of inadequate response to existing topical medications within 6 months preceding screening, or participants who failed systemic therapies intended to treat atopic dermatitis or a history of intolerance to topical therapy * Have a body mass index of 18.0 to 38.0 kilograms per square meter (kg/m²), inclusive * Male participants who agree to use highly effective or effective methods of contraception, women not of childbearing potential and women of childbearing potential may participate in part B
Exclusion criteria
* Women who are pregnant and/or lactating * Participants who have received live vaccine(s) (including attenuated live vaccines) or Bacillus Calmette- Guérin within 35 days of screening * Have a history or presence of multiple or severe allergies or an anaphylactic reaction to prescription or nonprescription drugs * Have a known history of diabetes * Have fasting glucose level of ≥126 milligrams per deciliter (mg/dL) and glycated hemoglobin ≥6.5 percent (%) and/or taking anti-diabetes medications at screening * Have known history of osteoporosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline through Day 85 | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality is located in the Reported Adverse Event module. Drug related TEAEs are any untoward medical occurrences that either occurs postdose or presents prior to dosing yet becomes more severe postdose, and in the opinion of the investigator is possibly related to study drug. |
| Part B: Number of Participants With One or More TEAEs, SAEs and Other Non-serious AEs Considered by the Investigator to be Related to Study Drug Administration | Baseline through Day 183 | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality is located in the Reported Adverse Event module. Drug related TEAEs are any untoward medical occurrences that either occurs postdose or presents prior to dosing yet becomes more severe postdose, and in the opinion of the investigator is possibly related to study drug. Zero participants were analyzed in this outcome as study was terminated early. |
| Part C: Number of Participants With One or More TEAEs, SAEs and Other Non-serious AEs Considered by the Investigator to be Related to Study Drug Administration | Baseline through Day 44 | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality is located in the Reported Adverse Event module. Drug related TEAEs are any untoward medical occurrences that either occurs postdose or presents prior to dosing yet becomes more severe postdose, and in the opinion of the investigator is possibly related to study drug. Zero participants were analyzed in this outcome as study was terminated early. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Part C: Cmax of Prednisone and Prednisolone | Predose up to 12 hours post dose on day 14 and day 30 | Zero participants were analyzed in this outcome as study was terminated early. |
| PK: Part C: AUC of Prednisone and Prednisolone | Predose up to 12 hours post dose on day 14 and day 30 | Zero participants were analyzed in this outcome as study was terminated early. |
| Pharmacokinetics (PK): Part A and B: Maximum Observed Concentration (Cmax) of LY3872386 | Day 1: predose, end of infusion, 3 hours, 6 hours, and 12 hours postdose, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 postdose (Part A) | Cmax of LY3872386 is reported. |
| PK: Part A and B: Area Under the Concentration Versus Time Curve (AUC) of LY3872386 | Day 1: predose, end of infusion, 3 hours, 6 hours, and 12 hours postdose, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 postdose (Part A) | Area Under the Concentration Versus Time Curve from Time Zero to tlast (AUC\[0-tlast\]) and Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-inf\]) of LY3872386 is reported. |
Countries
United States
Participant flow
Pre-assignment details
The study was designed to include three parts (A, B, and C). Results are reported only for Part A, as Parts B and C were not initiated and the study was terminated early due to emerging nonclinical data. In Part A, single-ascending dose (SAD), of the LY3872386 (SAD Cohorts 1 and 2 and the sentinel pair in SAD Cohort 3,) was administered to healthy participants on Day 1, followed by a 12-week follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Low Dose LY3872386 Participants received a single low dose of LY3872386 administered IV in healthy participants. | 6 |
| Part A: Mid-dose LY3872386 Participants received a single mid-dose of LY3872386 administered IV in healthy participants. | 6 |
| Part A: High Dose LY3872386 Participants received a single high dose of LY3872386 administered IV in healthy participants. | 1 |
| Part A: Placebo Placebo administered IV in healthy participants. | 5 |
| Total | 18 |
Baseline characteristics
| Characteristic | Part A: Low Dose LY3872386 | Part A: Mid-dose LY3872386 | Part A: High Dose LY3872386 | Part A: Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 1 Participants | 5 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 0 Participants | 4 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 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 |
| Race (NIH/OMB) White | 2 Participants | 4 Participants | 1 Participants | 5 Participants | 12 Participants |
| Region of Enrollment United States | 6 Participants | 6 Participants | 1 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 0 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 1 Participants | 3 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 1 | 0 / 5 |
| other Total, other adverse events | 2 / 6 | 3 / 6 | 0 / 1 | 0 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 1 | 0 / 5 |
Outcome results
Primary
Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration
A summary of SAEs and other non-serious adverse events (AEs), regardless of causality is located in the Reported Adverse Event module. Drug related TEAEs are any untoward medical occurrences that either occurs postdose or presents prior to dosing yet becomes more severe postdose, and in the opinion of the investigator is possibly related to study drug.
Time frame: Baseline through Day 85
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Low Dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs | 0 participants |
| Part A: Low Dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | AEs | 0 participants |
| Part A: Low Dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs | 0 participants |
| Part A: Mid-dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs | 2 participants |
| Part A: Mid-dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | AEs | 2 participants |
| Part A: Mid-dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs | 0 participants |
| Part A: High Dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs | 0 participants |
| Part A: High Dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs | 0 participants |
| Part A: High Dose LY3872386 | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | AEs | 0 participants |
| Part A: Placebo IV | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | TEAEs | 0 participants |
| Part A: Placebo IV | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | AEs | 0 participants |
| Part A: Placebo IV | Part A: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs) and Other Non-serious Adverse Events (AEs) Considered by the Investigator to be Related to Study Drug Administration | SAEs | 0 participants |
Primary
Part B: Number of Participants With One or More TEAEs, SAEs and Other Non-serious AEs Considered by the Investigator to be Related to Study Drug Administration
A summary of SAEs and other non-serious adverse events (AEs), regardless of causality is located in the Reported Adverse Event module. Drug related TEAEs are any untoward medical occurrences that either occurs postdose or presents prior to dosing yet becomes more severe postdose, and in the opinion of the investigator is possibly related to study drug. Zero participants were analyzed in this outcome as study was terminated early.
Time frame: Baseline through Day 183
Population: Zero participants were analyzed for this outcome. Data were not captured as study was terminated early, and no participant were enrolled into Part B.
Primary
Part C: Number of Participants With One or More TEAEs, SAEs and Other Non-serious AEs Considered by the Investigator to be Related to Study Drug Administration
A summary of SAEs and other non-serious adverse events (AEs), regardless of causality is located in the Reported Adverse Event module. Drug related TEAEs are any untoward medical occurrences that either occurs postdose or presents prior to dosing yet becomes more severe postdose, and in the opinion of the investigator is possibly related to study drug. Zero participants were analyzed in this outcome as study was terminated early.
Time frame: Baseline through Day 44
Population: Zero participants were analyzed for this outcome. Data were not captured as study was terminated early, and no participant were enrolled into Part C.
Secondary
Pharmacokinetics (PK): Part A and B: Maximum Observed Concentration (Cmax) of LY3872386
Cmax of LY3872386 is reported.
Time frame: Day 1: predose, end of infusion, 3 hours, 6 hours, and 12 hours postdose, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 postdose (Part A)
Population: All enrolled participants who received at least one dose of LY3872386 and had evaluable PK data in Part A. Zero participants were analyzed for Part B. Data were not captured as study was terminated early, and no participant were enrolled into Part B.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Low Dose LY3872386 | Pharmacokinetics (PK): Part A and B: Maximum Observed Concentration (Cmax) of LY3872386 | 2.54 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 16.9 |
| Part A: Mid-dose LY3872386 | Pharmacokinetics (PK): Part A and B: Maximum Observed Concentration (Cmax) of LY3872386 | 7.89 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 16.3 |
| Part A: High Dose LY3872386 | Pharmacokinetics (PK): Part A and B: Maximum Observed Concentration (Cmax) of LY3872386 | NA micrograms per milliliter (µg/mL) | — |
Secondary
PK: Part A and B: Area Under the Concentration Versus Time Curve (AUC) of LY3872386
Area Under the Concentration Versus Time Curve from Time Zero to tlast (AUC\[0-tlast\]) and Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-inf\]) of LY3872386 is reported.
Time frame: Day 1: predose, end of infusion, 3 hours, 6 hours, and 12 hours postdose, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 postdose (Part A)
Population: All enrolled participants who received at least one dose of LY3872386 and had evaluable PK data in Part A. Zero participants were analyzed for Part B. Data were not captured as study was terminated early, and no participant were enrolled into Part B.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Low Dose LY3872386 | PK: Part A and B: Area Under the Concentration Versus Time Curve (AUC) of LY3872386 | AUC(0-tlast) of LY3872386 | 55.7 microgram*hour per milliliter(µg*hr/mL) | Geometric Coefficient of Variation 15.6 |
| Part A: Low Dose LY3872386 | PK: Part A and B: Area Under the Concentration Versus Time Curve (AUC) of LY3872386 | AUC(0-∞) of LY3872386 | 65.8 microgram*hour per milliliter(µg*hr/mL) | Geometric Coefficient of Variation 18.6 |
| Part A: Mid-dose LY3872386 | PK: Part A and B: Area Under the Concentration Versus Time Curve (AUC) of LY3872386 | AUC(0-tlast) of LY3872386 | 328 microgram*hour per milliliter(µg*hr/mL) | Geometric Coefficient of Variation 19.7 |
| Part A: Mid-dose LY3872386 | PK: Part A and B: Area Under the Concentration Versus Time Curve (AUC) of LY3872386 | AUC(0-∞) of LY3872386 | 337 microgram*hour per milliliter(µg*hr/mL) | Geometric Coefficient of Variation 20.3 |
| Part A: High Dose LY3872386 | PK: Part A and B: Area Under the Concentration Versus Time Curve (AUC) of LY3872386 | AUC(0-tlast) of LY3872386 | NA microgram*hour per milliliter(µg*hr/mL) | — |
| Part A: High Dose LY3872386 | PK: Part A and B: Area Under the Concentration Versus Time Curve (AUC) of LY3872386 | AUC(0-∞) of LY3872386 | NA microgram*hour per milliliter(µg*hr/mL) | — |
Secondary
PK: Part C: AUC of Prednisone and Prednisolone
Zero participants were analyzed in this outcome as study was terminated early.
Time frame: Predose up to 12 hours post dose on day 14 and day 30
Population: Zero participants were analyzed for this outcome. Data were not captured as study was terminated early, and no participant were enrolled into Part C.
Secondary
PK: Part C: Cmax of Prednisone and Prednisolone
Zero participants were analyzed in this outcome as study was terminated early.
Time frame: Predose up to 12 hours post dose on day 14 and day 30
Population: Zero participants were analyzed for this outcome. Data were not captured as study was terminated early, and no participant were enrolled into Part C.