Healthy
Conditions
Brief summary
The main purpose of this study is to learn more about how LY3526318 affects blood flow to the skin in healthy women. For each participant, the study will last up to 28 days and Part B will last up to 78 days, including screening and follow-up.
Interventions
DRUGLY3526318
Administered orally.
DRUGPlacebo
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Must be healthy female participants as determined by medical history and physical examination --Female participants must be nonpregnant and not lactating, or of nonchildbearing potential (either surgically sterilized \[for example (e.g.) tubal occlusion, hysterectomy, bilateral salpingectomy\] or physiologically incapable of becoming pregnant, or postmenopausal with amenorrhea for at least 12 consecutive months) * Must have a body-mass index of 18 to 30 kilograms per square meter, inclusive * Must be willing to follow specific study procedures including * No drugs (except study drug, hormonal contraceptives) 7 days prior to each assessment and until discharge from Clinical Research Unit (CRU) * No chocolate, alcohol, or caffeine containing products 24 hours prior to initiation of each assessment and until discharge * A complete 4 hour fast (water is allowed) prior to cinnamaldehyde (CA) assessment * Must have suitable skin characteristics for the dermal CA challenge procedures and measured through Laser Doppler Imaging (LDI)
Exclusion criteria
* Must not be currently enrolled in or discontinued within the last 30 days or 5 half-lives of the study drug (whichever is longer), from a clinical study involving an investigational product or any type of medical research judged not compatible with this study * Must not have received treatment with biological agents (such as monoclonal antibodies, including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing * Must not have a history or presence of medical illness including, but not limited to, any cardiovascular, hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease, convulsions, or any clinically significant laboratory abnormality that would preclude study participation * Must not have an abnormality in the 12-lead electrocardiogram (ECG) or confirmed Frederica's corrected QT interval greater than (\>) 470 millisecond (msec) * Must not have a history of clinically significant multiple or severe drug allergies or severe post-treatment hypersensitivity reactions * Must avoid excessive tanning * Must not use lotions, oils, depilatory preparations, makeup, or other topical treatments on the arms on a regular basis or have used any topical treatments within 7 days prior to start of the first study day * Must not be a habitual and heavy consumer of coffee or caffeinated beverages (more than approximately 4 cups of tea, coffee, or cola drinks/day) or who cannot refrain from caffeinated beverages 24 hours prior to CA application * Must not be drinking alcohol 24 hours prior to each assessment * Must not be around second-hand smoke 24 hours prior to CA application or use nicotine-containing products. Ex-smokers should have ceased smoking at least 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | 3 hours post LY3526318 dose (pre-CA challenge), 3.3 hours post LY3526318 dose (post-CA challenge) | CA-induced DBF was measured by laser doppler imaging (LDI). Least Squares (LS) mean was determined by analysis of variance (ANOVA) model with treatment, period, sequence, time and treatment\*time interaction as fixed factors and subject within sequence as a random factor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | 3 hours post LY3526318 dose (pre-CA challenge), 3.3 hours post LY3526318 dose (post-CA challenge) | CA-induced DBF was measured by LSCI. LS mean was determined by ANOVA model with treatment, period, sequence, time and treatment\*time interaction as fixed factors and subject within sequence as a random factor. |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318 | Predose, 3 hours and 24 hours after each LY3526318 dose (days 1 through 50) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318 |
| PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | Predose, 3 hours and 24 hours after each LY3526318 dose (days 1 through 50) | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 |
| Plasma Concentrations of LY3526318 at 3 and 24 Hours | 3 hours and 24 hours post dose | Plasma Concentrations of LY3526318 at 3 and 24 Hours |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Sequence 1:
Period 1: Participant received placebo orally.
Period 2: Participants received 10 mg LY3526318 orally.
Period 3: Participants received 100 mg LY3526318 orally.
Period 4: Participants received 30 mg LY3526318 orally.
Sequence 2:
Period 1: Participant received 10 mg LY3526318 orally.
Period 2: Participants received 30 mg LY3526318 orally.
Period 3: Participants received Placebo orally.
Period 4: Participants received 100 mg LY3526318 orally.
Sequence 3:
Period 1: Participant received 30 mg LY3526318 orally.
Period 2: Participants received 100 mg LY3526318 orally.
Period 3: Participants received 10 mg LY3526318 orally.
Period 4: Participants received Placebo orally.
Sequence 4:
Period 1: Participant received 100 mg LY3526318 orally.
Period 2: Participants received Placebo orally.
Period 3: Participants received 30 mg LY3526318 orally.
Period 4: Participants received 10 mg LY3526318 orally. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 1 | 0 | 0 |
| Washout 1(14 Days) | Positive Drug Screen | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 29 years STANDARD_DEVIATION 6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment Belgium | 16 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 0 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 / 14 | 0 / 16 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 11 / 14 | 9 / 16 | 5 / 15 | 5 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI)
CA-induced DBF was measured by laser doppler imaging (LDI). Least Squares (LS) mean was determined by analysis of variance (ANOVA) model with treatment, period, sequence, time and treatment\*time interaction as fixed factors and subject within sequence as a random factor.
Time frame: 3 hours post LY3526318 dose (pre-CA challenge), 3.3 hours post LY3526318 dose (post-CA challenge)
Population: All participants who received LY3526318 or placebo at least once and had at least one reliable post-dose pharmacodynamic measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA Concentration (conc): Vehicle, Type: Region of Interest (ROI) | -9.46 Perfusion unit | Standard Error 6.45 |
| Placebo | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: Vehicle, Type: Entire Image | -14.22 Perfusion unit | Standard Error 3.28 |
| Placebo | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 3%, Type: Region of Interest) ROI | 811.66 Perfusion unit | Standard Error 98.22 |
| Placebo | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 3%, Type: Entire Image | 213.82 Perfusion unit | Standard Error 37.75 |
| Placebo | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 10% , Type: Region of Interest (ROI) | 1264.46 Perfusion unit | Standard Error 88.61 |
| Placebo | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 10% , Type: Entire Image | 610.17 Perfusion unit | Standard Error 65.79 |
| 10 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 10% , Type: Entire Image | 606.28 Perfusion unit | Standard Error 65.79 |
| 10 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 3%, Type: Entire Image | 177.17 Perfusion unit | Standard Error 37.75 |
| 10 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA Concentration (conc): Vehicle, Type: Region of Interest (ROI) | -6.96 Perfusion unit | Standard Error 6.45 |
| 10 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 3%, Type: Region of Interest) ROI | 757.83 Perfusion unit | Standard Error 98.22 |
| 10 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: Vehicle, Type: Entire Image | -15.1 Perfusion unit | Standard Error 3.28 |
| 10 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 10% , Type: Region of Interest (ROI) | 1233.80 Perfusion unit | Standard Error 88.61 |
| 30 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: Vehicle, Type: Entire Image | -12.34 Perfusion unit | Standard Error 3.28 |
| 30 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 3%, Type: Region of Interest) ROI | 771.15 Perfusion unit | Standard Error 98.22 |
| 30 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 3%, Type: Entire Image | 191.32 Perfusion unit | Standard Error 37.75 |
| 30 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 10% , Type: Entire Image | 419.15 Perfusion unit | Standard Error 65.79 |
| 30 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 10% , Type: Region of Interest (ROI) | 1165.69 Perfusion unit | Standard Error 88.61 |
| 30 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA Concentration (conc): Vehicle, Type: Region of Interest (ROI) | -14.82 Perfusion unit | Standard Error 6.45 |
| 100 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 10% , Type: Region of Interest (ROI) | 1049.57 Perfusion unit | Standard Error 88.61 |
| 100 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 10% , Type: Entire Image | 357.93 Perfusion unit | Standard Error 65.79 |
| 100 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: Vehicle, Type: Entire Image | -13.57 Perfusion unit | Standard Error 3.28 |
| 100 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 3%, Type: Entire Image | 179.95 Perfusion unit | Standard Error 37.75 |
| 100 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA Concentration (conc): Vehicle, Type: Region of Interest (ROI) | -7.78 Perfusion unit | Standard Error 6.45 |
| 100 mg LY3526318 | Decrease in Cinnamaldehyde (CA)-Induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Doppler Imaging (LDI) at 3 Hours Post-dose (LDI) | Ring/CA conc: 3%, Type: Region of Interest) ROI | 758.66 Perfusion unit | Standard Error 98.22 |
Comparison: Ring/CA conc: Vehicle, Type: ROIp-value: 0.7590% CI: [-10.66, 15.65]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: ROIp-value: 0.590% CI: [-18.49, 7.76]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: ROIp-value: 0.8390% CI: [-11.48, 14.84]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: Entire Imagep-value: 0.8490% CI: [-7.91, 6.15]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: Entire Imagep-value: 0.6690% CI: [-5.13, 8.9]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: Entire Imagep-value: 0.8890% CI: [-6.38, 7.68]ANOVA
Comparison: Ring/CA conc: 3% Type: ROIp-value: 0.5490% CI: [-200.7, 93.05]ANOVA
Comparison: Ring/CA conc: 3% Type: ROIp-value: 0.6590% CI: [-187.01, 105.98]ANOVA
Comparison: Ring/CA conc: 3% Type: ROIp-value: 0.5590% CI: [-199.87, 93.88]ANOVA
Comparison: Ring/CA conc: 3%, Type: Entire Imagep-value: 0.1890% CI: [-81.85, 8.56]ANOVA
Comparison: Ring/CA conc: 3%, Type: Entire Imagep-value: 0.4190% CI: [-67.58, 22.59]ANOVA
Comparison: Ring/CA conc: 3%, Type: Entire Imagep-value: 0.2290% CI: [-79.06, 11.34]ANOVA
Comparison: Ring/CA conc: 10%, Type: ROIp-value: 0.7490% CI: [-183.08, 121.76]ANOVA
Comparison: Ring/CA conc: 10%, Type: ROIp-value: 0.2890% CI: [-250.79, 53.25]ANOVA
Comparison: Ring/CA conc: 10%, Type: ROIp-value: 0.0290% CI: [-367.31, -62.48]ANOVA
Comparison: Ring/CA conc: 10% , Type: Entire Imagep-value: 0.9390% CI: [-81.44, 73.66]ANOVA
Comparison: Ring/CA conc: 10% , Type: Entire Imagep-value: <0.000190% CI: [-268.37, -113.67]ANOVA
Comparison: Ring/CA conc: 10%, Type: Entire Imagep-value: <0.000190% CI: [-329.79, -174.68]ANOVA
Secondary
Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI)
CA-induced DBF was measured by LSCI. LS mean was determined by ANOVA model with treatment, period, sequence, time and treatment\*time interaction as fixed factors and subject within sequence as a random factor.
Time frame: 3 hours post LY3526318 dose (pre-CA challenge), 3.3 hours post LY3526318 dose (post-CA challenge)
Population: All participants who received LY3526318 or placebo at least once and had at least one reliable post-dose pharmacodynamic measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: Vehicle, Type: Region of Interest (ROI) | -18.60 Perfusion unit | Standard Error 3.49 |
| Placebo | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: Vehicle, Type: Entire Image | -13.50 Perfusion unit | Standard Error 3.61 |
| Placebo | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 3%, Type: Region of Interest (ROI) | 217.47 Perfusion unit | Standard Error 26.49 |
| Placebo | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 3%, Type: Entire Image | 61.23 Perfusion unit | Standard Error 12.13 |
| Placebo | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 10%, Type: Region of Interest (ROI) | 306.68 Perfusion unit | Standard Error 16.98 |
| Placebo | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 10%, Type: Entire Image | 165.07 Perfusion unit | Standard Error 19.74 |
| 10 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 10%, Type: Entire Image | 175.09 Perfusion unit | Standard Error 19.74 |
| 10 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 3%, Type: Entire Image | 49.92 Perfusion unit | Standard Error 12.13 |
| 10 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: Vehicle, Type: Region of Interest (ROI) | -18.66 Perfusion unit | Standard Error 3.49 |
| 10 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 3%, Type: Region of Interest (ROI) | 199.09 Perfusion unit | Standard Error 26.49 |
| 10 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: Vehicle, Type: Entire Image | -14.79 Perfusion unit | Standard Error 3.61 |
| 10 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 10%, Type: Region of Interest (ROI) | 313.96 Perfusion unit | Standard Error 16.98 |
| 30 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: Vehicle, Type: Entire Image | -12.06 Perfusion unit | Standard Error 3.61 |
| 30 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 3%, Type: Region of Interest (ROI) | 214.50 Perfusion unit | Standard Error 26.49 |
| 30 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 3%, Type: Entire Image | 58.04 Perfusion unit | Standard Error 12.13 |
| 30 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 10%, Type: Entire Image | 111.44 Perfusion unit | Standard Error 19.74 |
| 30 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 10%, Type: Region of Interest (ROI) | 285.98 Perfusion unit | Standard Error 16.98 |
| 30 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: Vehicle, Type: Region of Interest (ROI) | -19.19 Perfusion unit | Standard Error 3.49 |
| 100 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 10%, Type: Region of Interest (ROI) | 271.90 Perfusion unit | Standard Error 16.98 |
| 100 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 10%, Type: Entire Image | 85.57 Perfusion unit | Standard Error 19.74 |
| 100 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: Vehicle, Type: Entire Image | -11.66 Perfusion unit | Standard Error 3.61 |
| 100 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 3%, Type: Entire Image | 50.77 Perfusion unit | Standard Error 12.13 |
| 100 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: Vehicle, Type: Region of Interest (ROI) | -16.07 Perfusion unit | Standard Error 3.49 |
| 100 mg LY3526318 | Decrease in CA-induced Dermal Blood Flow (DBF) Relative to Placebo Measured by Laser Speckle Contrast Imaging (LSCI) at 3 Hours Post-dose (LSCI) | Ring/CA conc: 3%, Type: Region of Interest (ROI) | 2017.36 Perfusion unit | Standard Error 26.49 |
Comparison: Ring/CA conc: Vehicle, Type: ROIp-value: 0.9990% CI: [-8.28, 8.15]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: ROIp-value: 0.9190% CI: [-8.78, 7.6]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: ROIp-value: 0.6190% CI: [-5.69, 10.74]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: Entire Imagep-value: 0.890% CI: [-9.58, 7]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: Entire Imagep-value: 0.7790% CI: [-6.83, 9.72]ANOVA
Comparison: Ring/CA conc: Vehicle, Type: Entire Imagep-value: 0.7190% CI: [-6.45, 10.14]ANOVA
Comparison: Ring/CA conc: 3%, Type: ROIp-value: 0.3890% CI: [-53.27, 16.51]ANOVA
Comparison: Ring/CA conc: 3%, Type: ROIp-value: 0.8990% CI: [-37.76, 31.83]ANOVA
Comparison: Ring/CA conc: 3%, Type: ROIp-value: 0.6390% CI: [-45, 24.77]ANOVA
Comparison: Ring/CA conc: 3%, Type: Entire Imagep-value: 0.2190% CI: [-26.21, 3.58]ANOVA
Comparison: Ring/CA conc: 3%, Type: Entire Imagep-value: 0.7290% CI: [-18.04, 11.67]ANOVA
Comparison: Ring/CA conc: 3%, Type: Entire Imagep-value: 0.2590% CI: [-25.35, 4.44]ANOVA
Comparison: Ring/CA conc: 10%, Type: ROIp-value: 0.6990% CI: [-22.71, 37.25]ANOVA
Comparison: Ring/CA conc: 10%, Type: ROIp-value: 0.2590% CI: [-50.6, 9.2]ANOVA
Comparison: Ring/CA conc: 10%, Type: ROIp-value: 0.0690% CI: [-64.77, -4.81]ANOVA
Comparison: Ring/CA conc: 10% Type: Entire Imagep-value: 0.5190% CI: [-15.4, 35.42]ANOVA
Comparison: Ring/CA conc: 10% Type: Entire Imagep-value: <0.00190% CI: [-78.98, -28.29]ANOVA
Comparison: Ring/CA conc: 10% Type: Entire Imagep-value: <0.000190% CI: [-104.91, -54.09]ANOVA
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318
Time frame: Predose, 3 hours and 24 hours after each LY3526318 dose (days 1 through 50)
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318 | NA nanogram*hour per milliliter (ng*h/mL) |
| 10 mg LY3526318 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318 | NA nanogram*hour per milliliter (ng*h/mL) |
| 30 mg LY3526318 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318 | NA nanogram*hour per milliliter (ng*h/mL) |
Secondary
PK: Maximum Observed Drug Concentration (Cmax) of LY3526318
PK: Maximum Observed Drug Concentration (Cmax) of LY3526318
Time frame: Predose, 3 hours and 24 hours after each LY3526318 dose (days 1 through 50)
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | NA micrograms per milliliter (ug/mL) |
| 10 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | NA micrograms per milliliter (ug/mL) |
| 30 mg LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | NA micrograms per milliliter (ug/mL) |
Secondary
Plasma Concentrations of LY3526318 at 3 and 24 Hours
Plasma Concentrations of LY3526318 at 3 and 24 Hours
Time frame: 3 hours and 24 hours post dose
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentrations of LY3526318 at 3 and 24 Hours | 3 Hours | 231.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 71.4 |
| Placebo | Plasma Concentrations of LY3526318 at 3 and 24 Hours | 24 Hours | 64.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 70.5 |
| 10 mg LY3526318 | Plasma Concentrations of LY3526318 at 3 and 24 Hours | 3 Hours | 627.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 92.2 |
| 10 mg LY3526318 | Plasma Concentrations of LY3526318 at 3 and 24 Hours | 24 Hours | 138.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 123.8 |
| 30 mg LY3526318 | Plasma Concentrations of LY3526318 at 3 and 24 Hours | 3 Hours | 3669.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 55.3 |
| 30 mg LY3526318 | Plasma Concentrations of LY3526318 at 3 and 24 Hours | 24 Hours | 854.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 84.4 |