Healthy
Conditions
Brief summary
The purpose of this study is to assess study drug activity by giving LY3316531 or placebo into a vein in the arm and then measuring blood flow of the skin, after capsaicin is applied to skin's surface. The study will last about 16 weeks inclusive of the screening period.
Interventions
DRUGLY3316531
Administered IV
DRUGPlacebo
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be healthy males * Must be abstinent or use condoms with spermicide as well as 1 additional highly effective method of contraception or effective method of contraception during the study and for 5 months following dosing of study drug * Must have a body mass index between 18 to 32.0 kilogram per meter square (kg/m²), inclusive, and a minimum body weight of 50 kilogram (kg) * Must have suitable skin characteristics for the dermal capsaicin challenge and have demonstrated at least a 100 percent (%) increase in dermal flow following capsaicin challenge as part of the screening procedures and measured through laser Doppler imaging (LDI)
Exclusion criteria
* Must not have evidence of clinically significant active infection, fever of 100.5 degrees Fahrenheit (°F) (38 degrees Centigrade (°C)) or above, at baseline * Must not show evidence of active or latent tuberculosis (TB) * Must not have received live, attenuated live, or non-live vaccine(s) within 28 days of screening or intend to receive during the study * Must not be immunocompromised * Must not have received treatment with biologic agents (such as monoclonal antibodies, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing * Must not have significant allergies to humanised monoclonal antibodies * Have a history of multiple or severe allergies or has had an anaphylactic reaction to prescription or nonprescription drugs or food * Must not have had any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin * Must not have eczema, scleroderma, psoriasis, dermatitis, keloids, tumors, ulcers, burns, flaps, or grafts on their forearm or other abnormality of the skin that may interfere with the study assessments * Must avoid excess tanning throughout the study and cannot cover forearms for 24 hours prior to each treatment period * Must not have excessive hair growth on the volar surface of the forearm or currently using lotions, oils, depilatory preparations, or other topical treatments on a regular basis that cannot be discontinued for the duration of the study; participant must not have used any topical treatments within 7 days of the start of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Capsaicin-Induced Dermal Blood Flow Following LY3316531 Compared to Placebo | Baseline, Day 24 | To assess target neutralization of calcitonin gene-related peptide by LY3316531 versus placebo, the capsaicin-induced dermal blood flow was measured at baseline (before administration of LY3316531 or placebo) as well as 24 days after a single intravenous dose of LY3316531 or placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3316531 | Pre-dose, end of infusion (30min), and 2 hours (h), 6h, 24h, 10 days, 24 days, 38 days, 52 days, 66 days and 80 days post-dose | Pharmacokinetics: Maximum Concentration (Cmax) of LY3316531 was reported. |
| Pharmacokinetics: Area Under Drug Concentration-Time Curve From Zero to Infinity (AUC[0 ∞]) of LY3316531 | Pre-dose, end of infusion (30min), and 2 hours (h), 6h, 24h, 10 days, 24 days, 38 days, 52 days, 66 days and 80 days post-dose | Pharmacokinetics: Area Under Drug Concentration-Time Curve From Zero to Infinity (AUC\[0 ∞\]) of LY3316531 was reported |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo as a single saline IV infusion.
Capsaicin-induced DBF: Topical doses of 20 microliter (µL) capsaicin \[1000 microgram (µg)/20 microliter (µL)\] applied to 2 different locations on the participant's forearm to induce an increase in dermal blood flow. A 20 µL topical dose of vehicle was applied to a third location on the forearm. | 4 |
| 300 mg LY3316531 Participants received a single 300 mg LY3316531 IV infusion.
Capsaicin-induced DBF: Topical doses of 20 microliter (µL) capsaicin (1000 microgram (µg)/20 µL) applied to 2 different locations on the participant's forearm to induce an increase in dermal blood flow. A 20 µL topical dose of vehicle was applied to a third location on the forearm. | 12 |
| Total | 16 |
Baseline characteristics
| Characteristic | Placebo | Total | 300 mg LY3316531 |
|---|---|---|---|
| Age, Continuous | 41.0 years STANDARD_DEVIATION 7.7 | 30.2 years STANDARD_DEVIATION 10.3 | 26.6 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 16 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 16 Participants | 12 Participants |
| Region of Enrollment Belgium | 4 Participants | 16 Participants | 12 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 16 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 12 |
| other Total, other adverse events | 2 / 4 | 9 / 12 |
| serious Total, serious adverse events | 0 / 4 | 0 / 12 |
Outcome results
Primary
Change From Baseline in Capsaicin-Induced Dermal Blood Flow Following LY3316531 Compared to Placebo
To assess target neutralization of calcitonin gene-related peptide by LY3316531 versus placebo, the capsaicin-induced dermal blood flow was measured at baseline (before administration of LY3316531 or placebo) as well as 24 days after a single intravenous dose of LY3316531 or placebo
Time frame: Baseline, Day 24
Population: All participants who received at least one injection of LY3316531 or Placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Capsaicin-Induced Dermal Blood Flow Following LY3316531 Compared to Placebo | 327.19 milliliter/100gram/minute (mL/100g/min) | Standard Deviation 67.02 |
| 300 mg LY3316531 | Change From Baseline in Capsaicin-Induced Dermal Blood Flow Following LY3316531 Compared to Placebo | 63.65 milliliter/100gram/minute (mL/100g/min) | Standard Deviation 53.31 |
p-value: <0.001t-test, 1 sided
Secondary
Pharmacokinetics: Area Under Drug Concentration-Time Curve From Zero to Infinity (AUC[0 ∞]) of LY3316531
Pharmacokinetics: Area Under Drug Concentration-Time Curve From Zero to Infinity (AUC\[0 ∞\]) of LY3316531 was reported
Time frame: Pre-dose, end of infusion (30min), and 2 hours (h), 6h, 24h, 10 days, 24 days, 38 days, 52 days, 66 days and 80 days post-dose
Population: All participants who received an injection of LY3316531 and contributed PK samples for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Area Under Drug Concentration-Time Curve From Zero to Infinity (AUC[0 ∞]) of LY3316531 | 42200 microgram*hour per milliliter (µg*h/mL) | Geometric Coefficient of Variation 16 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY3316531
Pharmacokinetics: Maximum Concentration (Cmax) of LY3316531 was reported.
Time frame: Pre-dose, end of infusion (30min), and 2 hours (h), 6h, 24h, 10 days, 24 days, 38 days, 52 days, 66 days and 80 days post-dose
Population: All participants who received an injection of LY3316531 and contributed PK samples for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY3316531 | 88.2 microgram per milliliter (µg/mL) | Geometric Coefficient of Variation 15 |