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| ID | Type | Description | Link |
|---|---|---|---|
| I5W-EW-LBCB | Other Identifier | Eli Lilly and Company |
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Elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in some participants.
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The purposes of this study are to look at safety, how well the study drug is tolerated, how much of the study drug gets into the blood stream, and how long it takes the body to get rid of it when given to healthy Japanese and non-Japanese participants as multiple doses. In addition, effects of 28-day oral dosing of LY3031207 on the amount of a cholesterol-lowering drug (simvastatin) that gets into the blood stream and how long the body takes to get rid of it will be determined. The effects of LY3031207 after single and 28-day dosing on blood pressure will also be studied. Information about any side effects that may occur will be collected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Daily oral administration of placebo for 28 days. Dose will match corresponding LY3031207 dosage. |
|
| LY3031207 | Experimental | Daily oral administration of 25 milligrams (mg) LY3031207 up to 450 mg LY3031207 for 28 days. |
|
| Celecoxib | Active Comparator | Daily oral administration of 400 mg celecoxib for 28 days. Positive control for LY3031207. |
|
| LY3031207 + Simvastatin | Other | Daily oral administration of 75 mg LY3031207 or 225 mg LY3031207 for 28 days. Single, oral 10 mg simvastatin open-label dose administered before and after 28-day dosing of LY3031207. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Capsules administered orally |
| |
| LY3031207 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | A treatment emergent adverse event (TEAE) is defined as an adverse event (AE) that occurs postdose or that is present predose and becomes more severe postdose. AEs presented are of all causalities and all severities. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Baseline to study completion (treatment completion and follow-up, up to 35 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | Maximum concentration (Cmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Predose up to 48 hours post last dose at Day 28 |
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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. | Honolulu | Hawaii |
Study enrolled participants of both Japanese and non-Japanese decent. Participants were pooled regardless of ethnicity. Participants assigned to 75 milligrams (mg) LY3031207 and 225 mg LY3031207 underwent identical procedures as those assigned to 25 mg LY3031207 with the addition of 10 mg open-label simvastatin administration on Days -3 and 28.
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| ID | Title | Description |
|---|---|---|
| FG000 | 25 mg LY3031207 | Daily oral administration of 25 milligrams (mg) LY3031207 for 28 days. |
| FG001 | 75 mg LY3031207 and Simvastatin | Daily oral administration of 75 mg LY3031207 for up to 28 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| FG002 | 225 mg LY3031207 and Simvastatin | Daily oral administration of 225 mg LY3031207 for up to 22 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Day -3 only. |
| FG003 | Placebo With or Without Simvastatin | Daily oral administration of placebo for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| FG004 | 400 mg Celecoxib With or Without Simvastatin | Daily oral administration of 400 mg celecoxib for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who received at least dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 25 mg LY3031207 | Daily oral administration of 25 milligrams (mg) LY3031207 for 28 days. |
| BG001 | 75 mg LY3031207 and Simvastatin | Daily oral administration of 75 mg LY3031207 for up to 28 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| 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 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | A treatment emergent adverse event (TEAE) is defined as an adverse event (AE) that occurs postdose or that is present predose and becomes more severe postdose. AEs presented are of all causalities and all severities. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | No | Baseline to study completion (treatment completion and follow-up, up to 35 weeks) |
|
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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 With or Without Simvastatin | Daily oral administration of placebo for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 15.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
Lilly voluntarily discontinued dosing of LY3031207 for all participants in LBCB because of early discontinuation criteria being met. Data for some endpoints (including blood pressure and Japanese comparison) were incomplete for the planned analyses.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| C000627901 | LY3031207 |
| D000068579 | Celecoxib |
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Drug |
Administered orally |
|
| Celecoxib | Drug | Administered orally |
|
| Simvastatin | Drug | Administered orally |
|
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207 | Area under the concentration versus time curve in a dosing interval (AUC[0-tau]) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Predose up to 48 hours post last dose at Day 28 |
| Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207 | Time of maximum concentration (Tmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Predose up to 48 hours post last dose at Day 28 |
| Pharmacokinetics: Maximum Concentration (Cmax) of Simvastatin | Predose up to 48 hours post dose at Day -3 and Day 28 |
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin | Area under the concentration versus time curve over the range of all measureable concentrations (AUC[0-tlast]) of simvastatin. | Predose up to 48 hours post dose at Day -3 and Day 28 |
| Pharmacokinetics: Time of Maximum Concentration (Tmax) of Simvastatin | Predose up to 48 hours post dose at Day -3 and Day 28 |
| Change From Baseline to Day 28 in Urinary Prostacyclin I (PGI) Metabolite Excretion | Baseline, Predose up to 12 hours prior to last dose at Day 28 |
| Change From Baseline to Day 28 in Urinary Prostaglandin E (PGE) Metabolite Excretion | Baseline, Predose up to time of last dose at Day 28 |
| Change From Baseline to Day 28 in Urinary Thromboxane A (TXA) Metabolite Excretion | Baseline, Predose up to 12 hours prior to last dose at Day 28 |
| United States |
| Sponsor Decision |
|
| BG002 | 225 mg LY3031207 and Simvastatin | Daily oral administration of 225 mg LY3031207 for up to 22 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Day -3 only. |
| BG003 | Placebo With or Without Simvastatin | Daily oral administration of placebo for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| BG004 | 400 mg Celecoxib With or Without Simvastatin | Daily oral administration of 400 mg celecoxib for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| BG005 | 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 |
|
Daily oral administration of 75 mg LY3031207 for up to 28 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| OG002 | 225 mg LY3031207 and Simvastatin | Daily oral administration of 225 mg LY3031207 for up to 22 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Day -3 only. |
| OG003 | Placebo With or Without Simvastatin | Daily oral administration of placebo for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| OG004 | 400 mg Celecoxib With or Without Simvastatin | Daily oral administration of 400 mg celecoxib for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. |
| OG005 | 10 mg Simvastatin | Oral administration of 10 mg open-label simvastatin on Days -3 and 28 for participants randomized to 75 mg LY3031207, 225 mg LY3031207 (Day -3 only), placebo, or celecoxib. Adverse events occurring following simvastatin dosing on Day -3 but prior to study drug dosing on Day 1 were counted under simvastatin. |
|
|
| Secondary | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | Maximum concentration (Cmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Participants who received at least one dose of LY3031207 with evaluable Cmax data at Day 28. Participants who had incomplete data due to early discontinuation were not analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms/milliliter (ng/mL) | Predose up to 48 hours post last dose at Day 28 |
|
|
|
| Secondary | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207 | Area under the concentration versus time curve in a dosing interval (AUC[0-tau]) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Participants who received at least one dose of LY3031207 with evaluable AUC (0-tau) data at Day 28. Participants who had incomplete data due to early discontinuation were not analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours/milliliter (hr*ng/mL) | Predose up to 48 hours post last dose at Day 28 |
|
|
|
| Secondary | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207 | Time of maximum concentration (Tmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Participants who received at least one dose of LY3031207 with evaluable Tmax data at Day 28. Participants who had incomplete data due to early discontinuation were not analyzed. | Posted | Geometric Mean | Full Range | hours | Predose up to 48 hours post last dose at Day 28 |
|
|
|
| Secondary | Pharmacokinetics: Maximum Concentration (Cmax) of Simvastatin | Participants dosed with 75 mg LY3031207 from Days 1 through 28 and with oral administration of 10 mg open-label simvastatin on Days -3 and 28 and who had complete pharmacokinetic profiles following both simvastatin dosing events. Participants who had incomplete data due to early discontinuation were not analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms/milliliter (ng/mL) | Predose up to 48 hours post dose at Day -3 and Day 28 |
|
|
|
| Secondary | Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin | Area under the concentration versus time curve over the range of all measureable concentrations (AUC[0-tlast]) of simvastatin. | Participants dosed with 75 mg LY3031207 from Days 1 through 28 and with oral administration of 10 mg open-label simvastatin on Days -3 and 28 and who had complete pharmacokinetic profiles following both simvastatin dosing events. Participants who had incomplete data due to early discontinuation were not analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours/milliliter (hr*ng/mL) | Predose up to 48 hours post dose at Day -3 and Day 28 |
|
|
|
| Secondary | Pharmacokinetics: Time of Maximum Concentration (Tmax) of Simvastatin | Participants dosed with 75 mg LY3031207 from Days 1 through 28 and with oral administration of 10 mg open-label simvastatin on Days -3 and 28 and who had complete pharmacokinetic profiles following both simvastatin dosing events. Participants who had incomplete data due to early discontinuation were not analyzed. | Posted | Median | Full Range | hours | Predose up to 48 hours post dose at Day -3 and Day 28 |
|
|
|
| Secondary | Change From Baseline to Day 28 in Urinary Prostacyclin I (PGI) Metabolite Excretion | Zero participants were analyzed. Data not collected. | Posted | Baseline, Predose up to 12 hours prior to last dose at Day 28 |
|
|
| Secondary | Change From Baseline to Day 28 in Urinary Prostaglandin E (PGE) Metabolite Excretion | Zero participants were analyzed. Data not collected. | Posted | Baseline, Predose up to time of last dose at Day 28 |
|
|
| Secondary | Change From Baseline to Day 28 in Urinary Thromboxane A (TXA) Metabolite Excretion | Zero participants were analyzed. Data not collected. | Posted | Baseline, Predose up to 12 hours prior to last dose at Day 28 |
|
|
| 0 |
| 6 |
| 1 |
| 6 |
| EG001 | 25 mg LY3031207 | Daily oral administration of 25 milligrams (mg) LY3031207 for 28 days. | 0 | 8 | 3 | 8 |
| EG002 | 75 mg LY3031207 and Simvastatin | Daily oral administration of 75 mg LY3031207 for up to 28 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Days -3 and 28. | 0 | 10 | 5 | 10 |
| EG003 | 225 mg LY3031207 and Simvastatin | Daily oral administration of 225 mg LY3031207 for up to 22 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Day -3 only. | 2 | 9 | 9 | 9 |
| EG004 | 400 mg Celecoxib With or Without Simvastatin | Daily oral administration of 400 mg celecoxib for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. | 0 | 6 | 1 | 6 |
| EG005 | 10 mg Simvastatin | Oral administration of 10 mg open-label simvastatin on Days -3 and 28 for participants randomized to 75 mg LY3031207, 225 mg LY3031207 (Day -3 only), placebo, or celecoxib. Adverse events occurring following simvastatin dosing on Day -3 but prior to study drug dosing on Day 1 were counted under simvastatin. | 0 | 27 | 3 | 27 |
| Constipation | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Sensitivity of teeth | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 15.0 | Systematic Assessment |
|
| Irritability | General disorders | MedDRA 15.0 | Systematic Assessment |
|
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 15.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 15.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA 15.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 15.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 15.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 15.0 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 15.0 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 15.0 | Systematic Assessment |
|
Not provided
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |