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| ID | Type | Description | Link |
|---|---|---|---|
| H9P-EW-LNCF | Other Identifier | Eli Lilly and Company |
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The purpose of this study is to determine how warfarin might affect LY2216684 and how giving LY2216684 might affect warfarin in the body. Information about any side effects that may occur will also be collected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Warfarin, LY2216684 + Warfarin | Experimental | Period 1: Single 10-milligram (mg) warfarin oral dose on Day 1; Washout Period of at least 14 days; Period 2: 18-mg LY2216684 oral dose, once daily on Days 1 to 12, with single 10-mg warfarin oral dose coadministered on Day 3. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Warfarin | Drug | 10-mg warfarin oral dose |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of S-Warfarin | Least Squares (LS) geometric mean was based on AUC0-∞ of S-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) of S-Warfarin | Least Squares (LS) geometric mean was based on Cmax of S-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
| Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of S-Warfarin | This outcome was measured based on Tmax of S-warfarin on Day 1 of Period 1 when warfarin was administered alone (reference) and on Day 3 of Period 2 when coadministered with LY2216684 (test). | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of R-Warfarin | Least Squares (LS) geometric mean was based on AUC0-∞ of R-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
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Inclusion Criteria:
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 |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Dallas | Texas |
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| ID | Title | Description |
|---|---|---|
| FG000 | Warfarin, LY2216684 + Warfarin | Period 1: Single 10-milligram (mg) warfarin oral dose on Day 1; Washout Period of at least 14 days; Period 2: 18-mg LY2216684 oral dose, once daily on Days 1 to 12, with single 10-mg warfarin oral dose coadministered on Day 3. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
|
| ||||||||||||||||||
| Period 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Warfarin, LY2216684 + Warfarin | Period 1: Single 10-milligram (mg) warfarin oral dose on Day 1; Washout Period of at least 14 days; Period 2: 18-mg LY2216684 oral dose, once daily on Days 1 to 12, with single 10-mg warfarin oral dose coadministered on Day 3. |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of S-Warfarin | Least Squares (LS) geometric mean was based on AUC0-∞ of S-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | The analysis population included participants who received at least 1 dose of warfarin and had evaluable concentration data. | Posted | Geometric Mean | 90% Confidence Interval | nanogram*hour per milliliter (ng*hr/mL) | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
|
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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 | 10 mg Warfarin + 18 mg LY2216684 (Test) | Period 2: Day -1=participant admission; Days 1 to 12=18-mg LY2216684 oral dose, once daily; Day 3=single 10-mg warfarin oral dose; Day 13=discharge. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D014859 | Warfarin |
| C568831 | alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol |
| ID | Term |
|---|---|
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 |
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| LY2216684 |
| Drug |
18-mg LY2216684 oral dose |
|
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) of R-Warfarin | Least Squares (LS) geometric mean was based on Cmax of R-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
| Pharmacokinetics: Time to Maximum Concentration (Tmax) of R-Warfarin | This outcome was measured based on Tmax of R-warfarin on Day 1 of Period 1 when warfarin was administered alone (reference) and on Day 3 of Period 2 when coadministered with LY2216684 (test). | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
| Pharmacodynamics: Area Under the Curve of the International Normalized Ratio (AUCINR) of Warfarin | The INR is the ratio of a participant's prothrombin time to a normal (control) sample. AUCINR was calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | Predose, 6, 12, 24, 48, 72, 96, 120, 144 hours post-warfarin administration on Days 1 and 3 |
| Pharmacodynamics: Maximum Observed International Normalized Ratio (INRmax) | INR is the ratio of a participant's prothrombin time to a normal (control) sample. INRmax was calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | Predose, 6, 12, 24, 48, 72, 96, 120, 144 hours post-warfarin administration on Days 1 and 3 |
| United States |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| OG001 | 10 mg Warfarin Alone (Reference) | Period 1: Day -1=participant admission; Day 1=single 10-mg warfarin oral dose; Day 11=discharge. Washout Period: at least 14 days between last dose in Period 1 and first dose in Period 2. |
|
|
|
| Primary | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of S-Warfarin | Least Squares (LS) geometric mean was based on Cmax of S-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | The analysis population included participants who received at least 1 dose of warfarin and had evaluable concentration data. | Posted | Geometric Mean | 90% Confidence Interval | nanogram per milliliter (ng/mL) | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
|
|
|
|
| Primary | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of S-Warfarin | This outcome was measured based on Tmax of S-warfarin on Day 1 of Period 1 when warfarin was administered alone (reference) and on Day 3 of Period 2 when coadministered with LY2216684 (test). | The analysis population included participants who had at least 1 dose of warfarin and had evaluable concentration data. | Posted | Median | Full Range | hour (h) | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
|
|
|
|
| Secondary | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of R-Warfarin | Least Squares (LS) geometric mean was based on AUC0-∞ of R-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | The analysis population included participants who had at least 1 dose of warfarin and evaluable concentration data. | Posted | Geometric Mean | 90% Confidence Interval | ng*h/mL | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
|
|
|
|
| Secondary | Pharmacokinetics: Maximum Plasma Concentration (Cmax) of R-Warfarin | Least Squares (LS) geometric mean was based on Cmax of R-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | The analysis population included participants who had at least 1 dose of warfarin and evaluable concentration data. | Posted | Geometric Mean | 90% Confidence Interval | ng/mL | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
|
|
|
|
| Secondary | Pharmacokinetics: Time to Maximum Concentration (Tmax) of R-Warfarin | This outcome was measured based on Tmax of R-warfarin on Day 1 of Period 1 when warfarin was administered alone (reference) and on Day 3 of Period 2 when coadministered with LY2216684 (test). | The analysis population included participants who had at least 1 dose of warfarin and evaluable concentration data. | Posted | Median | Full Range | h | Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3 |
|
|
|
|
| Secondary | Pharmacodynamics: Area Under the Curve of the International Normalized Ratio (AUCINR) of Warfarin | The INR is the ratio of a participant's prothrombin time to a normal (control) sample. AUCINR was calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | The analysis population included participants who had at least 1 dose of warfarin and evaluable concentration data. | Posted | Number | 90% Confidence Interval | ratio | Predose, 6, 12, 24, 48, 72, 96, 120, 144 hours post-warfarin administration on Days 1 and 3 |
|
|
|
|
| Secondary | Pharmacodynamics: Maximum Observed International Normalized Ratio (INRmax) | INR is the ratio of a participant's prothrombin time to a normal (control) sample. INRmax was calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2. | The analysis population included participants who had at least 1 dose of warfarin and evaluable concentration data. | Posted | Number | 90% Confidence Interval | ratio | Predose, 6, 12, 24, 48, 72, 96, 120, 144 hours post-warfarin administration on Days 1 and 3 |
|
|
|
|
| 0 |
| 16 |
| 8 |
| 16 |
| EG001 | 10 mg Warfarin Alone (Reference) | Period 1: Day -1=participant admission; Day 1=single 10-mg warfarin oral dose; Day 11=discharge. Washout Period: at least 14 days between last dose in Period 1 and first dose in Period 2. | 0 | 18 | 6 | 18 |
| EG002 | 18 mg LY2216684 Alone | Period 2: 18-mg LY2216684 oral dose, once daily on Days 1 to 12. | 0 | 16 | 8 | 16 |
| Vision blurred | Eye disorders | MedDRA 13.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Lip dry | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Feeling jittery | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Vessel puncture site pain | General disorders | MedDRA 13.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Loss of consciousness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
|
| Urinary hesitation | Renal and urinary disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
| Peripheral coldness | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
Not provided
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |