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| ID | Type | Description | Link |
|---|---|---|---|
| J2D-MC-CVAB | Other Identifier | Eli Lilly and Company | |
| 2019-003613-34 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY3526318 | Experimental | 10 milligrams (mg), 30 mg and 100 mg LY3526318 administered orally in three of four study periods. |
|
| Placebo | Placebo Comparator | Placebo administered orally in one of four study periods. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY3526318 | Drug | Administered orally. |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 3 hours post LY3526318 dose (pre-CA challenge), 3.3 hours post LY3526318 dose (post-CA challenge) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 3 hours post LY3526318 dose (pre-CA challenge), 3.3 hours post LY3526318 dose (post-CA challenge) |
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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
Must have suitable skin characteristics for the dermal CA challenge procedures and measured through Laser Doppler Imaging (LDI)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg | Leuven | 3000 | Belgium |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1: Placebo,10 mg LY3526318,100 mg LY3526318,30 mg LY3526318 | Period 1: Participant received placebo orally. Period 2: Participants received 10 milligrams (mg) LY3526318 orally. Period 3: Participants received 100 mg LY3526318 orally. Period 4: Participants received 30 mg LY3526318 orally. |
| FG001 | Sequence 2: 10 mg LY3526318,30 mg LY3526318, Placebo,100 mg LY3526318 | 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. |
| FG002 | Sequence 3: 30 mg LY3526318,100 mg LY3526318,10 mg LY3526318, Placebo | 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. |
| FG003 | Sequence 4: 100 mg LY3526318, Placebo, 30 mg LY3526318,10 mg LY3526318 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Washout 1(14 Days) |
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| Period 2 |
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| Washout 2 (14 Days) |
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| Period 3 |
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| Washout 3 (14 Days) |
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| Period 4 |
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All participants who received at least one dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All participants who received LY3526318 or placebo at least once and had at least one reliable post-dose pharmacodynamic measurement. | Posted | Least Squares Mean | Standard Error | Perfusion unit | 3 hours post LY3526318 dose (pre-CA challenge), 3.3 hours post LY3526318 dose (post-CA challenge) |
|
Baseline Up To 50 Days
All participants who received at least one dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received Placebo orally. | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 22.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 | ClinicalTrials.gov@lilly.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 15, 2019 | Feb 22, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 11, 2020 | Feb 22, 2021 | SAP_001.pdf |
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| Drug |
Administered orally. |
|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3526318 | 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) |
| PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | Predose, 3 hours and 24 hours after each LY3526318 dose (days 1 through 50) |
| Plasma Concentrations of LY3526318 at 3 and 24 Hours | Plasma Concentrations of LY3526318 at 3 and 24 Hours | 3 hours and 24 hours post dose |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
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| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Region of Enrollment | Count of Participants | Participants | No |
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| 10 mg LY3526318 |
Participant received 10 mg LY3526318 orally. |
| OG002 | 30 mg LY3526318 | Participant received 30 mg LY3526318 orally. |
| OG003 | 100 mg LY3526318 | Participant received 100 mg LY3526318 orally. |
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| 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. | All participants who received LY3526318 or placebo at least once and had at least one reliable post-dose pharmacodynamic measurement. | Posted | Least Squares Mean | Standard Error | Perfusion unit | 3 hours post LY3526318 dose (pre-CA challenge), 3.3 hours post LY3526318 dose (post-CA challenge) |
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|
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| 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 | All participants who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*h/mL) | Predose, 3 hours and 24 hours after each LY3526318 dose (days 1 through 50) |
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| Secondary | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | PK: Maximum Observed Drug Concentration (Cmax) of LY3526318 | All participants who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per milliliter (ug/mL) | Predose, 3 hours and 24 hours after each LY3526318 dose (days 1 through 50) |
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| Secondary | Plasma Concentrations of LY3526318 at 3 and 24 Hours | Plasma Concentrations of LY3526318 at 3 and 24 Hours | All participants who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 3 hours and 24 hours post dose |
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| 14 |
| 0 |
| 14 |
| 11 |
| 14 |
| EG001 | LY3526318 10 mg | Participants received 10 mg LY3526318 orally. | 0 | 16 | 0 | 16 | 9 | 16 |
| EG002 | LY3526318 30 mg | Participants received 30 mg LY3526318 orally. | 0 | 15 | 0 | 15 | 5 | 15 |
| EG003 | LY3526318 100 mg | Participants received 100 mg LY3526318 orally. | 0 | 15 | 0 | 15 | 5 | 15 |
| Vessel puncture site haematoma | General disorders | MedDRA 22.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Pyuria | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Tinea pedis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Vulvovaginal candidiasis | Infections and infestations | MedDRA 22.1 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Wound | Injury, poisoning and procedural complications | MedDRA 22.1 | Systematic Assessment |
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| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 22.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 22.1 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
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| Leukocyturia | Renal and urinary disorders | MedDRA 22.1 | Systematic Assessment |
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| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA 22.1 | Systematic Assessment |
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| Diastolic hypotension | Vascular disorders | MedDRA 22.1 | Systematic Assessment |
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| Ring/CA conc: Vehicle, Type: Entire Image |
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| Ring/CA conc: 3%, Type: Region of Interest (ROI) |
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| Ring/CA conc: 3%, Type: Entire Image |
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| Ring/CA conc: 10%, Type: Region of Interest (ROI) |
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| Ring/CA conc: 10%, Type: Entire Image |
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| 0.91 |
| Mean Difference (Final Values) |
| -0.59 |
| 2-Sided |
| 90 |
| -8.78 |
| 7.60 |
| Superiority |
| Ring/CA conc: Vehicle, Type: ROI | ANOVA | 0.61 | Mean Difference (Final Values) | 2.53 | 2-Sided | 90 | -5.69 | 10.74 | Superiority |
| Ring/CA conc: Vehicle, Type: Entire Image | ANOVA | 0.80 | Mean Difference (Final Values) | -1.29 | 2-Sided | 90 | -9.58 | 7.00 | Superiority |
| Ring/CA conc: Vehicle, Type: Entire Image | ANOVA | 0.77 | Mean Difference (Final Values) | 1.45 | 2-Sided | 90 | -6.83 | 9.72 | Superiority |
| Ring/CA conc: Vehicle, Type: Entire Image | ANOVA | 0.71 | Mean Difference (Final Values) | 1.85 | 2-Sided | 90 | -6.45 | 10.14 | Superiority |
| Ring/CA conc: 3%, Type: ROI | ANOVA | 0.38 | Mean Difference (Final Values) | -18.38 | 2-Sided | 90 | -53.27 | 16.51 | Superiority |
| Ring/CA conc: 3%, Type: ROI | ANOVA | 0.89 | Mean Difference (Final Values) | -2.97 | 2-Sided | 90 | -37.76 | 31.83 | Superiority |
| Ring/CA conc: 3%, Type: ROI | ANOVA | 0.63 | Mean Difference (Final Values) | -10.12 | 2-Sided | 90 | -45.00 | 24.77 | Superiority |
| Ring/CA conc: 3%, Type: Entire Image | ANOVA | 0.21 | Mean Difference (Final Values) | -11.31 | 2-Sided | 90 | -26.21 | 3.58 | Superiority |
| Ring/CA conc: 3%, Type: Entire Image | ANOVA | 0.72 | Mean Difference (Final Values) | -3.19 | 2-Sided | 90 | -18.04 | 11.67 | Superiority |
| Ring/CA conc: 3%, Type: Entire Image | ANOVA | 0.25 | Mean Difference (Final Values) | -10.46 | 2-Sided | 90 | -25.35 | 4.44 | Superiority |
| Ring/CA conc: 10%, Type: ROI | ANOVA | 0.69 | Mean Difference (Final Values) | 7.27 | 2-Sided | 90 | -22.71 | 37.25 | Superiority |
| Ring/CA conc: 10%, Type: ROI | ANOVA | 0.25 | Mean Difference (Final Values) | -20.70 | 2-Sided | 90 | -50.60 | 9.2 | Superiority |
| Ring/CA conc: 10%, Type: ROI | ANOVA | 0.06 | Mean Difference (Final Values) | -34.79 | 2-Sided | 90 | -64.77 | -4.81 | Superiority |
| Ring/CA conc: 10% Type: Entire Image | ANOVA | 0.51 | Mean Difference (Final Values) | 10.01 | 2-Sided | 90 | -15.4 | 35.42 | Superiority |
| Ring/CA conc: 10% Type: Entire Image | ANOVA | <0.001 | Mean Difference (Final Values) | -53.63 | 2-Sided | 90 | -78.98 | -28.29 | Superiority |
| Ring/CA conc: 10% Type: Entire Image | ANOVA | <.0001 | Mean Difference (Final Values) | -79.50 | 2-Sided | 90 | -104.91 | -54.09 | Superiority |
|