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| ID | Type | Description | Link |
|---|---|---|---|
| H8Y-MC-HBCH | Other Identifier | Eli Lilly and Company | |
| 2011-003033-34 | EudraCT Number |
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This study will explore how liver impairment affects blood levels of LY2140023 (a prodrug) and its active metabolite (LY404039).
The study included 4 groups, based on the Child-Pugh classification of hepatic impairment as follows:
Group 1: Participants with normal hepatic function (Control); Group 2: Participants with mild hepatic impairment (Child-Pugh class A); Group 3: Participants with moderate hepatic impairment (Child-Pugh class B); and Group 4: Participants with severe hepatic impairment (Child-Pugh class C).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY2140023 | Experimental | A single oral dose of 80 milligrams (mg) LY2140023 administered on Day 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2140023 | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2140023 and LY404039 | LY404039 is the active metabolite of LY2140023. AUC from zero to infinity AUC(0-∞) is presented. | Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose |
| Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of LY2140023 and LY404039 | LY404039 is the active metabolite of LY2140023. | Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose |
| Pharmacokinetics: Time of Maximal Concentration (Tmax) of LY2140023 and LY404039 | LY404039 is the active metabolite of LY2140023. | Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose |
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Inclusion Criteria:
Exclusion Criteria:
Are currently enrolled in, have completed or discontinued within the last 90 days from last dosing of an investigational product (other than the investigational product used in this study); or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Have known allergies to LY2140023, LY404039, related compounds, or any components of the formulation
Have previously discontinued after receiving at least 1 dose of LY2140023 or completed this study or any other study investigating LY2140023 and or LY404039
Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study
Have a history or presence of cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption (except cholecystectomy), metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
Have evidence of significant active neuropsychiatric disease (for example, manic depressive illness, schizophrenia, or depression)
Participants who answer 'yes' to either Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) or Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the Columbia Suicide Severity Rating Scale (C-SSRS), or answer "yes" to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior) on the "Suicidal Behavior" portion of the C-SSRS; and the ideation or behavior occurred within the past 3 months
Have increased risk of seizures based on a history of:
Known substance dependence unless approved prescription medication such as opiates, or known regular use of drugs of abuse and/or show positive findings on urinary drug screening
Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
Women who are pregnant or intend to get pregnant during the study or within 3 months after the last dose of investigational product
Women who are breast feeding or lactating
Have donated blood of more than 500 milliliters (mL) within the last 3 months prior to the screening
Are organ transplant participants or have taken immunosuppressants following any organ transplant
Have shown signs of variceal bleeding during the last 2 months prior to screening (except for participants with severe hepatic impairment, detailed in exclusion criterion)
Show evidence of irritable bowel syndrome or chronic diarrhea
Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), and are participants unwilling to stop alcohol consumption for 96 hours predose until after 48 hours post-dose (1 unit equals 12 ounces [oz] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
Have a clinically significant abnormality in the neurological examination
Participants judged prior to dosing to be at suicidal risk by the investigator
Participants who are unwilling to refrain from smoking from midnight prior to dosing until 6 hours postdose or are unable to abide by the Clinical Research Unit (CRU) restrictions
Are on total parenteral nutrition (TPN)
Take oral anticoagulants for therapeutic use
Exhibit any other condition, which, in the opinion of the investigator would preclude participation in the study
Show evidence of pruritus or skin exfoliation
Have an eosinophil count >1.5 x 10^9/liter (L)
Have electrolyte imbalance alerts (clinically significant changes in calcium magnesium, or sodium)
Control Participants:
Men: [(140 - age) x (weight in kilograms [kg])] / [72 x (serum creatinine in mg/100 mL)]; or [(140 - age) x (weight in kg)] / [0.81 x (serum creatinine in micromoles per liter [μmol/L])] Women in both of the above equations: (x 0.85)
Show evidence of significant active neuropsychiatric disease in the opinion of the investigator
Evidence of hepatitis B and/or positive hepatitis B surface antigen (HBsAg)
Show evidence of hepatitis C and/or positive hepatitis C antibody
Intend to use over-the-counter medication (including herbal remedies/health supplements) within 7 days prior to dosing, or prescription medication (other than hormone replacement therapy as described above) within 14 days prior to dosing
show evidence of any significant active disease other than that responsible for or associated with hepatic impairment
have a platelet count of less than 50 x 10^9 cells/L, unless after consultation with the Lilly Clinical Pharmacologist (CP), they are considered as acceptable for participation in the study
Show evidence of any significant active disease other than that responsible for or associated with moderate or severe hepatic impairment
Have shown signs of spontaneous bacterial peritonitis within 6 months prior to dosing
Have severe hyponatremia
Show evidence of significant active neuropsychiatric disease
Have hepatic encephalopathy (Grades 2 to 4)
Have hemoglobin concentrations <9.0 grams per deciliter (g/dL)
Show signs of hepatocellular carcinoma
Have a surgical portosystemic shunt
Have a platelet count of less than 40 x 10^9 cells/L (moderate impairment) or less than 30 x 10^9 cells/L (severe impairment), unless after consultation with the Lilly CP they are considered as acceptable for participation in the study
Have shown signs of variceal bleeding during the last 2 weeks prior to screening (severe hepatic impaired participants only)
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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. | Munich | 81241 |
Participants (Pts) were enrolled in Group 3 (moderate hepatic impairment) after satisfactory interim safety and pharmacokinetic (PK) data was obtained from ≥3 Pts in Group 2 (mild hepatic impairment). Pts were enrolled in Group 4 (severe hepatic impairment) after satisfactory interim safety and PK data was obtained from ≥3 Pts in Group 3.
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| ID | Title | Description |
|---|---|---|
| FG000 | LY2140023-Normal Hepatic Function | Participants with normal hepatic function received a single oral dose of 80 milligrams (mg) LY2140023 on Day 1. |
| FG001 | LY2140023-Mild Hepatic Impairment | Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1. |
| FG002 | LY2140023-Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1. |
| FG003 | LY2140023-Severe Hepatic Impairment | Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | LY2140023-Normal Hepatic Function | Participants with normal hepatic function received a single oral dose of 80 mg LY2140023 on Day 1. |
| BG001 | LY2140023-Mild Hepatic Impairment |
| 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 Concentration Time Curve (AUC) of LY2140023 and LY404039 | LY404039 is the active metabolite of LY2140023. AUC from zero to infinity AUC(0-∞) is presented. | All participants who received 1 dose of LY2140023, did not have an incidence of vomiting within 5 hours postdose, and had evaluable AUC(0-∞) data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter (ng*h/mL) | Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose |
|
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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 | LY2140023-Normal Hepatic Function | Participants with normal hepatic function received a single oral dose of 80 mg LY2140023 on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 14.0 | 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 |
|---|---|
| D048550 | Hepatic Insufficiency |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C534551 | LY 2140023 |
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| Germany |
| 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. | Balatonfüred | 8230 | Hungary |
| Entry Criteria Not Met |
|
| Withdrawal by Subject |
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| Adverse Event |
|
| Death |
|
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
| BG002 | LY2140023-Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1. |
| BG003 | LY2140023-Severe Hepatic Impairment | Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1. |
| OG002 | LY2140023-Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1. |
| OG003 | LY2140023-Severe Hepatic Impairment | Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1. |
|
|
| Primary | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of LY2140023 and LY404039 | LY404039 is the active metabolite of LY2140023. | All participants who received 1 dose of LY2140023, did not have an incidence of vomiting within 5 hours postdose, and had evaluable Cmax data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms/milliliter (ng/mL) | Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose |
|
|
|
| Primary | Pharmacokinetics: Time of Maximal Concentration (Tmax) of LY2140023 and LY404039 | LY404039 is the active metabolite of LY2140023. | All participants who received 1 dose of LY2140023, did not have an incidence of vomiting within 5 hours postdose, and had evaluable Tmax data. | Posted | Median | Full Range | hours | Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose |
|
|
|
| 0 |
| 7 |
| 5 |
| 7 |
| EG001 | LY2140023-Mild Hepatic Impairment | Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1. | 0 | 6 | 5 | 6 |
| EG002 | LY2140023-Moderate Hepatic Impairment | Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1. | 0 | 6 | 4 | 6 |
| EG003 | LY2140023-Severe Hepatic Impairment | Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1. | 0 | 7 | 0 | 7 |
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 14.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
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| Blood creatine phosphokinase increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Dizziness postural | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
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| Sleep disorder | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
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| LY404039 |
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| LY404039 |
|