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| ID | Type | Description | Link |
|---|---|---|---|
| I4M-MC-MRAB | Other Identifier | Eli Lilly |
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The purpose of this study is to investigate the safety and tolerability of LY2623091 after multiple oral dosing in healthy men and women of non-childbearing potential. Two cohorts of 16 subjects will participate in 2 dosing periods. Treatment assignment will be double-blind for LY2623091 and placebo (negative control), and open label for eplerenone (positive control).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 mg LY2623091 | Experimental | Daily by mouth for 7 days. |
|
| 10 mg LY2623091 | Experimental | Daily by mouth for 7 days. |
|
| 25 mg LY2623091 | Experimental | The anticipated dose of LY2623091 was revised down from the original proposed dose level of 100 mg based on safety and tolerability data. The 25 mg LY2623091 was administered daily by mouth for 7 days. |
|
| 0.3 mg LY2623091 | Experimental | The anticipated dose of LY2623091 was revised down from the original proposed dose level of up to 200 mg. The 0.3 mg LY2623091 was determined based on an interim analysis after the third dose level and was administered daily by mouth for 7 days. |
|
| Placebo | Placebo Comparator | Daily by mouth for 7 days. |
|
| 50 mg Eplerenone |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2623091 | Drug | Administered orally. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Clinically Significant Effects (Adverse Events) | A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section. | Baseline through 7 days for each treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamics: Serum to Urine Potassium Area Under the Concentration-Time Curve (AUC) Standardized for Urinary Excretion at Day 7 | A measure of the renal clearance of the potassium ion (K+). The Least Squares (LS) Mean value was adjusted for pre-challenge renal K+ clearance. | Day 7: 24 Hour (hr), 48hr and 72hr Postdose |
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Inclusion Criteria:
Are healthy men and women of non-childbearing potential as determined by medical history and physical examination.
Have given written informed consent prior to any study-specific procedures.
Are reliable and willing to make themselves available for the duration of the study and are willing to follow site-specific study procedures.
Have a body mass index (BMI) of between 19 and 32.5 kilograms per square meter (kg/m^2).
Have clinical laboratory test results within the normal reference range for the population or study site, or test results with acceptable deviations that are judged by the Investigator not to be clinically significant.
Have venous access sufficient to allow blood sampling per the protocol.
Have serum potassium levels within the normal range.
Are nonsmokers or smokers of less than or equal to 10 cigarettes per day.
Exclusion Criteria:
Are currently enrolled in, or have discontinued, within 60 days inclusive, a clinical trial involving an investigational drug, device or an off-label use of an approved drug, or are concurrently enrolled in any other type of medical research judged to be scientifically or medically incompatible with this study. Subjects who meet any of these criteria may be enrolled in this study but they cannot be dosed until at least 60 days following the last day of the previous investigational trial.
Have previously completed or withdrawn from this study or any other study investigating LY2623091.
Have a history or presence of medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine or neurological disease, or any clinically significant laboratory abnormality that is of a serious medical problem that would preclude study participation.
Have an abnormality in the 12-lead electrocardiogram (ECG), which increases the risks associated with participation in the study.
Are unwilling or unable to comply with the use of an electronic data capture system.
Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies, hepatitis C and/or positive hepatitis C antibody or hepatitis B and/or positive hepatitis B surface antigen.
Use and/or intend to use any medication for a medical condition that is not compatible with Inclusion Criterion. For medications that may be used in "healthy" subjects (example given: preventative and/or naturopathic agents, temporary symptom-relieving medications, and so forth) the following constraints must be observed:
Have donated blood of more than 50 milliliters (mL) within the last 60 days.
Have an average weekly alcohol intake that exceeds 21 units per week and/or subjects unwilling to stop alcohol within 48 hours of study enrollment and for the duration of the study.
Have an abnormally high blood pressure (supine or standing) defined as diastolic blood pressure greater than 95 millimeters of mercury (mmHg) and /or systolic blood pressure greater than 150 mmHg, confirmed by at least 1 repeat measurement.
Have serum potassium greater than the upper limit of normal.
Regularly use known drugs of abuse or show positive findings for such use on urinary drug screening.
Consumption of natural licorice and/or natural licorice-containing products and/or grapefruit and/or grapefruit juice within 7 days of first dosing and/or anticipated consumption during the study.
Consumption of methylxanthine-containing beverages and/or foods (example: coffee, tea, caffeinated soft drinks, chocolate) within 4 days of first dosing and/or anticipated consumption during the study.
Are unwilling to abstain from salt-substitutes containing potassium for the duration of the study.
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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. | Zuidlaren | 9471 GP |
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| ID | Title | Description |
|---|---|---|
| FG000 | 1 mg LY2623091 First Then 25 mg LY2623091 | 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. |
| FG001 | 1 mg LY2623091 First Then Placebo | 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. |
| FG002 | 1 mg LY2623091 First Then 50 mg Eplerenone | 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days. |
| FG003 | 50 mg Eplerenone First Then 25 mg LY2623091 | 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. |
| FG004 | 50 mg Eplerenone First Then Placebo | 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. |
| FG005 | Placebo First Then 25 mg LY2623091 | Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. |
| FG006 | 10 mg LY2623091 First Then 0.3 mg LY2623091 | 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before 0.3 mg LY2623091 daily by mouth for 7 days. |
| FG007 | 10 mg LY2623091 First Then Placebo | 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. |
| FG008 | 10 mg LY2623091 First Then 50 mg Eplerenone | 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days. |
| FG009 | 50 mg Eplerenone First Then 0.3 mg LY2623091 | 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days. |
| FG010 | Placebo Then 0.3 mg LY2623091 | Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Dosing Period |
| |||||||||||||
| Washout Period of at Least 7 Days |
| |||||||||||||
| Second Dosing Period |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 1 mg LY2623091 First Then 25 mg LY2623091 | 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. |
| BG001 | 1 mg LY2623091 First Then Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Number of Participants With Clinically Significant Effects (Adverse Events) | A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section. | All participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Baseline through 7 days for each treatment period |
|
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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 | Daily by mouth for 7 days. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 13.0 | 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 |
|---|---|
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
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| ID | Term |
|---|---|
| D000077545 | Eplerenone |
| ID | Term |
|---|---|
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 |
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Daily by mouth for 7 days. |
|
| Placebo | Drug | Administered orally. |
|
| Eplerenone | Drug | Administered orally. |
|
| Pharmacokinetics of LY2623091: Maximal Concentration (Cmax) at Day 6 |
Cmax estimated for LY2623091. |
| Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose |
| Pharmacokinetics LY2623091: Area Under the Concentration-Time Curve (AUC) at Day 6 | AUC from time 0, extrapolated to infinity, estimated for LY2623091. | Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose |
| Netherlands |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| COMPLETED |
|
| NOT COMPLETED |
|
1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days.
| BG002 | 1 mg LY2623091 First Then 50 mg Eplerenone | 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days. |
| BG003 | 50 mg Eplerenone First Then 25 mg LY2623091 | 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. |
| BG004 | 50 mg Eplerenone First Then Placebo | 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. |
| BG005 | Placebo First Then 25 mg LY2623091 | Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. |
| BG006 | 10 mg LY2623091 First Then 0.3 mg LY2623091 | 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before 0.3 mg LY2623091 daily by mouth for 7 days. |
| BG007 | 10 mg LY2623091 First Then Placebo | 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. |
| BG008 | 10 mg LY2623091 First Then 50 mg Eplerenone | 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days. |
| BG009 | 50 mg Eplerenone First Then 0.3 mg LY2623091 | 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days. |
| BG010 | Placebo Then 0.3 mg LY2623091 | Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days. |
| BG011 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
Daily by mouth for 7 days. |
| OG003 | 10 mg LY2623091 | Daily by mouth for 7 days. |
| OG004 | 25 mg LY2623091 | Daily by mouth for 7 days. |
| OG005 | 50 mg Eplerenone | Daily by mouth for 7 days. |
|
|
| Secondary | Pharmacodynamics: Serum to Urine Potassium Area Under the Concentration-Time Curve (AUC) Standardized for Urinary Excretion at Day 7 | A measure of the renal clearance of the potassium ion (K+). The Least Squares (LS) Mean value was adjusted for pre-challenge renal K+ clearance. | All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable. | Posted | Least Squares Mean | 95% Confidence Interval | liter per hour (L/h) | Day 7: 24 Hour (hr), 48hr and 72hr Postdose |
|
|
|
| Secondary | Pharmacokinetics of LY2623091: Maximal Concentration (Cmax) at Day 6 | Cmax estimated for LY2623091. | All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose |
|
|
|
| Secondary | Pharmacokinetics LY2623091: Area Under the Concentration-Time Curve (AUC) at Day 6 | AUC from time 0, extrapolated to infinity, estimated for LY2623091. | All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable. | Posted | Mean | Standard Deviation | microgram*hour per milliliter (µg*h/mL) | Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose |
|
|
|
| 0 |
| 16 |
| 6 |
| 16 |
| EG001 | 0.3 mg LY2623091 | Daily by mouth for 7 days. | 0 | 8 | 2 | 8 |
| EG002 | 1 mg LY2623091 | Daily by mouth for 7 days. | 0 | 8 | 5 | 8 |
| EG003 | 10 mg LY2623091 | Daily by mouth for 7 days. | 0 | 8 | 4 | 8 |
| EG004 | 25 mg LY2623091 | Daily by mouth for 7 days. | 0 | 8 | 6 | 8 |
| EG005 | 50 mg Eplerenone | Daily by mouth for 7 days. | 0 | 15 | 9 | 15 |
| Ocular hyperaemia | Eye disorders | MedDRA 13.0 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Gingivitis | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Lip dry | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Application site irritation | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Catheter site related reaction | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Vessel puncture site reaction | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Fungal skin infection | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Skin injury | Injury, poisoning and procedural complications | MedDRA 13.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 13.0 | Systematic Assessment |
|
| Epididymitis | Reproductive system and breast disorders | MedDRA 13.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dry throat | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
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| D005261 |
| Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |