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| ID | Type | Description | Link |
|---|---|---|---|
| H9P-EW-LNDZ | Other Identifier | Eli Lilly and Company |
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The study will evaluate how genetic profiles respond to LY2216684 and the effect of Quinidine on the pharmacokinetics (PK) of LY2216684 in a specific genetic profile. Side effects will be documented.
The human cytochrome P450 2C19 (CYP2C19) enzyme is a polymorphic enzyme yielding ultrarapid metabolizer, extensive metabolizer (EM), intermediate metabolizer, and poor metabolizer (PM) phenotypes. Enrollment in the study was limited to participants predicted to be CYP2C19 extensive metabolizers or CYP2C19 poor metabolizers, as determined by genotyping analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY2216684 + Quinidine (CYP2C19 poor metabolizers) | Experimental | Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 was administered on Day 1. Period 2 (Days 8-15): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11. |
|
| LY2216684 (CYP2C19 extensive metabolizers) | Experimental | Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 administered on Day 1. Period 2 (Days 8-15): EM participants did not participate in this period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2216684 | Drug |
| ||
| Quinidine |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-∞)] of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM) | Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations. | Predose up to 120 hours post administration of LY2216684 |
| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM) | Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations. | Predose up to 120 hours post administration of LY2216684 |
| Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM) | Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations. | Predose up to 120 hours post administration of LY2216684 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [(AUC(0-∞)] of LY2216684 + Quinidine in Cytochrome P450 (CYP)2C19 Poor Metabolizers (PM) | Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations. | Predose up to 120 hours post administration of quinidine |
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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 | LY2216684 + Quinidine (CYP2C19 Poor Metabolizers) | Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 was administered on Day 1. Period 2 (Days 8-15): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11. |
| FG001 | LY2216684 (CYP2C19 Extensive Metabolizers) | Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 administered on Day 1. Period 2 (Days 8-15): EM participants did not participate in this period. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (Days 1-7) |
| ||||||||||||||||
| Period 2 (Days 8-15) |
|
All enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | LY2216684 + Quinidine (CYP2C19 Poor Metabolizers) | Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 was administered on Day 1. Period 2 (Days 8-15): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11. |
| 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 to Infinity [AUC(0-∞)] of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM) | Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations. | Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. Participants who vomited within twice the median time to maximum observed drug concentration (tmax) following dosing of LY2216684 were excluded from the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter (ng*h/mL) | Predose up to 120 hours post administration of LY2216684 |
|
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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 | LY2216684 (CYP2C19 Extensive and Poor Metabolizers) | Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) or poor metabolizer (PM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 administered on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lacrimation increased | Eye disorders | MedDRA 14.1 | 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 |
|---|---|
| C568831 | alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol |
| D011802 | Quinidine |
| ID | Term |
|---|---|
| D002930 | Cinchona Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D011812 | Quinuclidines |
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| Drug |
|
|
| Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 + Quinidine in CYP2C19 Poor Metabolizers | Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations. | Predose up to 120 hours post administration of quinidine |
| Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of LY2216684 + Quinidine in CYP2C19 Poor Metabolizers | Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations. | Predose up to 120 hours post administration of quinidine |
| United States |
| NOT COMPLETED |
|
|
| BG001 | LY2216684 (CYP2C19 Extensive Metabolizers) | Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1. Period 2 (Days 8-15): EM participants did not participate in this period. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | LY2216684 (CYP2C19 Extensive Metabolizers) | Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 mg LY2216684 administered on Day 1. |
|
|
| Primary | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM) | Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations. | Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. Participants who vomited within twice the median time to maximum observed drug concentration (tmax) following dosing of LY2216684 were excluded from the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Predose up to 120 hours post administration of LY2216684 |
|
|
|
| Primary | Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM) | Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations. | Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. Participants who vomited within twice the median time to maximum observed drug concentration (tmax) following dosing of LY2216684 were excluded from the analysis. | Posted | Median | Full Range | hours | Predose up to 120 hours post administration of LY2216684 |
|
|
|
| Secondary | Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [(AUC(0-∞)] of LY2216684 + Quinidine in Cytochrome P450 (CYP)2C19 Poor Metabolizers (PM) | Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations. | Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter (ng*h/mL) | Predose up to 120 hours post administration of quinidine |
|
|
|
| Secondary | Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 + Quinidine in CYP2C19 Poor Metabolizers | Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations. | Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Predose up to 120 hours post administration of quinidine |
|
|
|
| Secondary | Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of LY2216684 + Quinidine in CYP2C19 Poor Metabolizers | Blood samples were collected prior to and up to 120 hours following coadministration of LY2216684 and quinidine on Day 11 (Period 2) for the measurement of LY2216684 plasma concentrations. | Participants who received at least 1 dose of LY2216684 and had evaluable LY2216684 plasma concentration data were included in the analysis. | Posted | Median | Full Range | hours | Predose up to 120 hours post administration of quinidine |
|
|
|
| 0 |
| 18 |
| 10 |
| 18 |
| EG001 | Quinidine (CYP2C19 Poor Metabolizers) | Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis. Period 2 (Days 8-11, prior to LY2216684 dose): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-11. | 0 | 7 | 1 | 7 |
| EG002 | LY2216684 + Quinidine (CYP2C19 Poor Metabolizers) | Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis. Period 2 (Days 11-15, following LY2216684 dose): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 11-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11. | 0 | 7 | 3 | 7 |
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Vessel puncture site pain | General disorders | MedDRA 14.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 14.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.1 | Systematic Assessment |
|
| Social avoidant behaviour | Psychiatric disorders | MedDRA 14.1 | Systematic Assessment |
|
| Urinary hesitation | Renal and urinary disorders | MedDRA 14.1 | Systematic Assessment |
|
| Testicular atrophy | Reproductive system and breast disorders | MedDRA 14.1 | Systematic Assessment |
|
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| D006572 |
| Heterocyclic Compounds, Bridged-Ring |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |