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| ID | Type | Description | Link |
|---|---|---|---|
| H6Q-MC-JCAX | Other Identifier | Eli Lilly and Company |
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The purpose of this study is to assess the effect of enzastaurin (LY317615), on a protein (enzyme CYP2C9) which is involved in the metabolic pathway of warfarin in participants with solid tumors or lymphomas. Information about any side effects that may occur will also be collected. This is a drug interaction study so the treatment of the disease will not be the main purpose of the study.
This is a Phase 1, open label, fixed sequence, 2 period study conducted in participants with solid tumors or lymphomas. The duration of participation in this study will be up to approximately 38 days not including screening, after which participants will be allowed to continue receiving enzastaurin. There is no planned duration for the extension phase of this study; participants will be allowed to continue to receive enzastaurin until fulfilling one of the criteria for discontinuation, such as unacceptable toxicity or disease progression.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| warfarin + enzastaurin | Experimental | On Day 1 of Period 1, a single 5-milligram (mg) oral dose of warfarin will be given, followed by at least a 7-day washout. Period 2: 500 mg enzastaurin administered orally once daily for at least 19 consecutive days and 5 mg warfarin administered as a single oral dose on Day 15. Safety Extension: Participants are allowed to continue receiving enzastaurin alone until disease progression or other discontinuation criteria are met. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| warfarin | Drug | Administered orally |
| |
| enzastaurin |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) of S-Warfarin and R-Warfarin | Cmax of S-Warfarin and R-Warfarin determined using Geometric Least Squares (LS) mean model that was estimated from a mixed-effects model with repeated measures (MMRM) that included treatment as a fixed effect (warfarin alone as reference, and warfarin with enzastaurin as test), participant as a random effect and random error term. | Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 hours postdose |
| Pharmacokinetics: Time of Maximal Plasma Concentration (Tmax) of S-Warfarin and R-Warfarin | Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 hours postdose | |
| Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of S-Warfarin and R-Warfarin | AUC(0-∞) determined using Geometric Least Squares (LS) mean model that was estimated from a mixed-effects model with repeated measures (MMRM) that included treatment as a fixed effect (warfarin alone as reference, and warfarin with enzastaurin as test), participant as a random effect and random error term. | Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 hours postdose |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) at Steady State of Enzastaurin, Its Principle Metabolites and Total Analyte | Cmax at steady state (Cmax,ss) of enzastaurin, the principle metabolite (LSN326020), and the total analytes (enzastaurin, LSN326020, LSN485912 and LSN2406799) when enzastaurin is administered alone and with warfarin. | Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours postdose |
Not provided
Inclusion Criteria:
Have given written informed consent approved by Eli Lilly and Company (Lilly) and the ethical review board (ERB) governing the site
Have a histologic or cytologic diagnosis of cancer (lymphoma or solid tumor), with clinical or radiologic evidence of locally advanced and/or metastatic disease for which no life-prolonging therapy exists (Note: participants with glioblastoma, known central nervous system (CNS) metastases and other hematologic malignancies [except lymphoma] are excluded from this study)
Men or women with reproductive potential must use an approved contraceptive method, if appropriate, during and for 3 months after discontinuation of study treatment. All methods of contraception should meet the criteria of highly effective contraceptives(failure rate of <1% per year) such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence, or vasectomized partner. Women with childbearing potential must have a negative serum pregnancy test ≤3 days prior to the first dosing day in the study (Period 1, Day 1).
Have a performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale and, in the investigator's opinion, are suitable for participation in the study
Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, anticancer hormone therapy, or other investigational therapy for at least 30 days prior to study entry (6 weeks for mitomycin-C or nitrosoureas), and have recovered from the acute effects of therapy
For participants with hormone refractory prostate cancer, the following exception is permitted:
Have adequate organ function including:
Electrolytes: Participants may be entered into the study, if the investigator's opinion is that any electrolyte disorders, including potassium <3.4 milliequivalent per liter (mEq/L), calcium <8.4 mg/dL, or magnesium <1.2 mEq/L, may be appropriately managed and stabilized by the time of the laboratory evaluation on the baseline day in Period 1. If electrolytes have not been stabilized during this time, the participant will be discontinued from the study.
Coagulation: normal prothrombin time/INR (PT/INR) and activated partial thromboplastin time (aPTT)
Have an estimated life expectancy, in the judgment of the investigator, which will permit the participant to complete the drug interaction phase and at least 1 cycle of the safety extension phase (if the participant were to take part in the safety extension)
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. | Bordeaux | 33076 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Warfarin + Enzastaurin | Period 1 Day 1 (of an 8-day period): 5 milligrams (mg) warfarin administered as a single oral dose. Period included at least a 7-day washout. Period 2 (19 up to 30 days): 500 mg enzastaurin administered orally once daily for at least 19 consecutive days and 5 mg warfarin administered as a single oral dose on Day 15. Safety Extension Period: Participants were allowed to continue receiving 500 mg enzastaurin orally once daily alone until disease progression or other discontinuation criteria were met. Participants were on study for up to a total of 8 months (Period 1, Period 2 and Safety Extension Period). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
|
| |||||||||||||||||||||
| Period 2 |
| ||||||||||||||||||||||
| Safety Extension |
|
All enrolled participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Warfarin + Enzastaurin | Period 1 Day 1 (of an 8-day period): 5 milligram (mg) warfarin administered as a single oral dose. Period included at least a 7-day washout. Period 2 (19 up to 30 days): 500 mg enzastaurin administered orally once daily for at least 19 consecutive days and 5 mg warfarin administered as a single oral dose on Day 15. Safety Extension Period: Participants were allowed to continue receiving 500 mg enzastaurin orally once daily alone until disease progression or other discontinuation criteria were met. Participants were on study for up to a total of 8 months (Period 1, Period 2 and Safety Extension Period). |
| 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: Maximum Plasma Concentration (Cmax) of S-Warfarin and R-Warfarin | Cmax of S-Warfarin and R-Warfarin determined using Geometric Least Squares (LS) mean model that was estimated from a mixed-effects model with repeated measures (MMRM) that included treatment as a fixed effect (warfarin alone as reference, and warfarin with enzastaurin as test), participant as a random effect and random error term. | All enrolled participants who were assigned to a treatment, received at least 1 dose of study treatment. | Posted | Least Squares Mean | 90% Confidence Interval | nanograms/milliliter (ng/mL) | Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 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 | Period 1 | Period 1 Day 1 (of an 8-day period): 5 milligrams (mg) warfarin administered as a single oral dose. Period included at least a 7-day washout. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | 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 |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| D014859 | Warfarin |
| C504878 | enzastaurin |
| ID | Term |
|---|---|
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 |
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| Drug |
Administered orally |
|
|
| Pharmacokinetics: Time of Maximal Plasma Concentration (Tmax) of Enzastaurin, Its Principle Metabolites and Total Analyte | Tmax at steady state (tmax,ss) of enzastaurin, the principle metabolite (LSN326020), and the total analytes (enzastaurin, LSN326020, LSN485912 and LSN2406799) when enzastaurin is administered alone and with warfarin. | Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours postdose |
| Pharmacokinetics: Area Under Concentration-Time Curve Over a Dosing Interval at Steady State (AUCss) of Enzastaurin, Its Principle Metabolites and Total Analyte | AUCss of enzastaurin, the principle metabolite (LSN326020), and the total analytes (enzastaurin, LSN326020, LSN485912 and LSN2406799) when enzastaurin is administered alone and with warfarin. | Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours postdose |
| Pharmacokinetics: Average Concentration During a Dosing Interval Steady State (Cav,ss) of Enzastaurin, Its Principle Metabolites and Total Analyte | Cav,ss of enzastaurin, the principle metabolite (LSN326020), and the total analytes (enzastaurin, LSN326020, LSN485912 and LSN2406799) when enzastaurin is administered alone and with warfarin. | Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours post dose |
| Pharmacodynamics: Maximum International Normalised Ratio (INRmax) Following Warfarin Alone | INRmax is the maximum INR over the time points after administration of warfarin alone. INR is the ratio of the actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from a mixed-effects model with repeated measures (MMRM) that included treatment as a fixed effect, and participant as a random effect and a random term error. | Period 1 (8 days): Predose on Day 1, up to 96 hours postdose or Period 2 (19 up to 30 days): Predose on Day 15, up to 96 hours post warfarin dose |
| Pharmacodynamics: Area Under International Normalised Ratio-time Curve AUC(INR) Following Warfarin Alone | AUC(INR) is the area under INR time curve over the time after administration of warfarin alone. INR is the ratio of actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from a mixed-effects model with repeated measures (MMRM) that included treatment as a fixed effect, and participant as a random effect and a random term error. | Period 1 (8 days): Predose on Day 1, up to 96 hours postdose or Period 2 (19 up to 30 days): Predose on Day 15, up to 96 hours post warfarin dose |
| Pharmacodynamics: Maximum International Normalised Ratio (INRmax) Following Concomitant Administration of Warfarin and Enzastaurin | INRmax is the maximum INR over the time points after administration of warfarin and enzastaurin. INR is the ratio of the actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from a mixed-effects model with repeated measures (MMRM) that included predose measurement of INR in warfarin alone (Period 1) as a covariate, treatment as a fixed effect, participant as a random effect and a random error term. (See Outcome Measure 8 for statistical analysis comparing reporting groups Warfarin and Warfarin co-administered with Enzastaurin) | Period 2 Day 15 (19 up to 30 days): Predose, up to 96 hours post warfarin dose |
| Pharmacodynamics: Area Under International Normalised Ratio-Time Curve AUC(INR) Following Concomitant Administration of Warfarin and Enzastaurin | AUC(INR) is the area under INR time curve over the time after administration of warfarin and enzastaurin. INR is the ratio of actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from a mixed-effects model with repeated measures (MMRM) that included predose measurement of INR in warfarin alone (Period 1) as a covariate, treatment as a fixed effect, participant as a random effect and a random error term. (See Outcome Measure 9 for statistical analysis comparing reporting groups Warfarin and Warfarin co-administered with Enzastaurin.) | Period 2 Day 15 (19 up to 30 days): Predose, up to 96 hours post warfarin dose |
| Pharmacodynamics: International Normalised Ratio (INR) Following Enzastaurin Alone | INR is the ratio of the actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from timepoint (Period 1 Lead-in Day, 0 and 4 hours at Period 2, Day 14) as fixed effect, participant as a random effect and a random error term. | Period 2 Day 14 (19 up to 30 days): Predose and 4 hours postdose |
| France |
| 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. | Dijon | 21079 | France |
| 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. | Lille | 59020 | France |
| 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. | Paris | 75908 | France |
| 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. | Rennes | 35062 | France |
| 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. | Saint-Herblain | 44800 | France |
| 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. | Toulouse | 31052 | France |
| NOT COMPLETED |
|
|
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Warfarin + Enzastaurin | Period 2 (19 up to 30 days): 500 mg enzastaurin administered orally once daily for at least 19 consecutive days and 5 mg warfarin administered as a single oral dose on Day 15. |
|
|
|
| Primary | Pharmacokinetics: Time of Maximal Plasma Concentration (Tmax) of S-Warfarin and R-Warfarin | All enrolled participants who were assigned to a treatment and received at least 1 dose of study treatment and had S-warfarin and R-warfarin tmax values. | Posted | Median | Full Range | hours | Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 hours postdose |
|
|
|
|
| Primary | Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of S-Warfarin and R-Warfarin | AUC(0-∞) determined using Geometric Least Squares (LS) mean model that was estimated from a mixed-effects model with repeated measures (MMRM) that included treatment as a fixed effect (warfarin alone as reference, and warfarin with enzastaurin as test), participant as a random effect and random error term. | All enrolled participants who were assigned to a treatment and received at least 1 dose of study treatment and had S-warfarin and R-warfarin AUC(0-∞) values. | Posted | Least Squares Mean | 90% Confidence Interval | nanograms*hours/milliliter (ng*h/mL) | Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 hours postdose |
|
|
|
|
| Secondary | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) at Steady State of Enzastaurin, Its Principle Metabolites and Total Analyte | Cmax at steady state (Cmax,ss) of enzastaurin, the principle metabolite (LSN326020), and the total analytes (enzastaurin, LSN326020, LSN485912 and LSN2406799) when enzastaurin is administered alone and with warfarin. | All enrolled participants who were assigned to a treatment and received at least 1 dose of study treatment and had Cmax,ss values. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomoles/liter (nmol/L) | Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours postdose |
|
|
|
| Secondary | Pharmacokinetics: Time of Maximal Plasma Concentration (Tmax) of Enzastaurin, Its Principle Metabolites and Total Analyte | Tmax at steady state (tmax,ss) of enzastaurin, the principle metabolite (LSN326020), and the total analytes (enzastaurin, LSN326020, LSN485912 and LSN2406799) when enzastaurin is administered alone and with warfarin. | All enrolled participants who were assigned to a treatment and received at least 1 dose of study treatment who had enzastaurin, LSN326020 and total analyte tmax,ss values. | Posted | Median | Full Range | hours | Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours postdose |
|
|
|
| Secondary | Pharmacokinetics: Area Under Concentration-Time Curve Over a Dosing Interval at Steady State (AUCss) of Enzastaurin, Its Principle Metabolites and Total Analyte | AUCss of enzastaurin, the principle metabolite (LSN326020), and the total analytes (enzastaurin, LSN326020, LSN485912 and LSN2406799) when enzastaurin is administered alone and with warfarin. | All enrolled participants who were assigned to a treatment and received at least 1 dose of study treatment who had enzastaurin, LSN326020 and total analyte AUC,ss values . | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomoles*hour/liter (nmol*h/L) | Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours postdose |
|
|
|
| Secondary | Pharmacokinetics: Average Concentration During a Dosing Interval Steady State (Cav,ss) of Enzastaurin, Its Principle Metabolites and Total Analyte | Cav,ss of enzastaurin, the principle metabolite (LSN326020), and the total analytes (enzastaurin, LSN326020, LSN485912 and LSN2406799) when enzastaurin is administered alone and with warfarin. | All enrolled participants who were assigned to a treatment and received at least 1 dose of study treatment who had enzastaurin, LSN326020 and total analyte Cav,ss values. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanomole/liter (nmol/L) | Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours post dose |
|
|
|
| Secondary | Pharmacodynamics: Maximum International Normalised Ratio (INRmax) Following Warfarin Alone | INRmax is the maximum INR over the time points after administration of warfarin alone. INR is the ratio of the actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from a mixed-effects model with repeated measures (MMRM) that included treatment as a fixed effect, and participant as a random effect and a random term error. | All enrolled participants who were assigned to a treatment, received at least 1 dose of study treatment and had at least 1 evaluable INRmax warfarin or warfarin/enzastaurin value. | Posted | Least Squares Mean | 90% Confidence Interval | ratio | Period 1 (8 days): Predose on Day 1, up to 96 hours postdose or Period 2 (19 up to 30 days): Predose on Day 15, up to 96 hours post warfarin dose |
|
|
|
|
| Secondary | Pharmacodynamics: Area Under International Normalised Ratio-time Curve AUC(INR) Following Warfarin Alone | AUC(INR) is the area under INR time curve over the time after administration of warfarin alone. INR is the ratio of actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from a mixed-effects model with repeated measures (MMRM) that included treatment as a fixed effect, and participant as a random effect and a random term error. | All enrolled participants who were assigned to a treatment, received at least 1 dose of study treatment and at least 1 evaluable warfarin or warfarin plus enzastaurin AUC(INR) value. | Posted | Least Squares Mean | 90% Confidence Interval | ratio | Period 1 (8 days): Predose on Day 1, up to 96 hours postdose or Period 2 (19 up to 30 days): Predose on Day 15, up to 96 hours post warfarin dose |
|
|
|
|
| Secondary | Pharmacodynamics: Maximum International Normalised Ratio (INRmax) Following Concomitant Administration of Warfarin and Enzastaurin | INRmax is the maximum INR over the time points after administration of warfarin and enzastaurin. INR is the ratio of the actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from a mixed-effects model with repeated measures (MMRM) that included predose measurement of INR in warfarin alone (Period 1) as a covariate, treatment as a fixed effect, participant as a random effect and a random error term. (See Outcome Measure 8 for statistical analysis comparing reporting groups Warfarin and Warfarin co-administered with Enzastaurin) | All enrolled participants who were assigned to a treatment, received at least 1 dose of study treatment and had at least 1 evaluable INRmax warfarin and enzastaurin value. | Posted | Geometric Mean | 90% Confidence Interval | ratio | Period 2 Day 15 (19 up to 30 days): Predose, up to 96 hours post warfarin dose |
|
|
|
| Secondary | Pharmacodynamics: Area Under International Normalised Ratio-Time Curve AUC(INR) Following Concomitant Administration of Warfarin and Enzastaurin | AUC(INR) is the area under INR time curve over the time after administration of warfarin and enzastaurin. INR is the ratio of actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from a mixed-effects model with repeated measures (MMRM) that included predose measurement of INR in warfarin alone (Period 1) as a covariate, treatment as a fixed effect, participant as a random effect and a random error term. (See Outcome Measure 9 for statistical analysis comparing reporting groups Warfarin and Warfarin co-administered with Enzastaurin.) | All enrolled participants who were assigned to a treatment, received at least 1 dose of study treatment and at least 1 evaluable AUC(INR) concomitant warfarin and enzastaurin value. | Posted | Geometric Mean | 90% Confidence Interval | ratio | Period 2 Day 15 (19 up to 30 days): Predose, up to 96 hours post warfarin dose |
|
|
|
| Secondary | Pharmacodynamics: International Normalised Ratio (INR) Following Enzastaurin Alone | INR is the ratio of the actual prothrombin time over normal prothrombin time. Geometric Least Squares (LS) mean model was used that was estimated from timepoint (Period 1 Lead-in Day, 0 and 4 hours at Period 2, Day 14) as fixed effect, participant as a random effect and a random error term. | All enrolled participants who were assigned to a treatment, received at least 1 dose of study treatment and at least 1 evaluable INR enzastaurin result. | Posted | Least Squares Mean | 90% Confidence Interval | ratio | Period 2 Day 14 (19 up to 30 days): Predose and 4 hours postdose |
|
|
|
|
| 0 |
| 13 |
| 5 |
| 13 |
| EG001 | Period 2, Prior to Warfarin Dose | Period 2 (19 up to 30 days): 500 mg enzastaurin administered orally once daily up to Day 14. | 0 | 12 | 8 | 12 |
| EG002 | Period 2, Post Warfarin Dose | Period 2 (19 up to 30 days): 500 mg enzastaurin administered orally once daily for at least 19 consecutive days and 5 mg warfarin administered as a single oral dose on Day 15. Enzastaurin administered up to 30 days total. | 0 | 10 | 7 | 10 |
| EG003 | Safety Extension | Safety Extension: Participants were allowed to continue receiving 500 mg enzastaurin orally once daily alone until disease progression or other discontinuation criteria are met. Participants were on study for up to a total 8 months (Period 1, Period 2 and Safety Extension). | 0 | 7 | 5 | 7 |
| Ocular icterus | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Iodine allergy | Immune system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Postoperative wound infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Vaginal infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Tooth avulsion | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Electrocardiogram qt prolonged | Investigations | MedDRA 14.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 14.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 14.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA 14.0 | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 14.0 | Systematic Assessment |
|
| Metrorrhagia | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
|
| Vulvovaginal pruritus | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 14.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
Not provided
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Median Difference (Final Values) |
| 2.50 |
| 2-Sided |
| 90 |
| -1.00 |
| 6.84 |
Median Difference (Final Values) is for R-warfarin. |
| Superiority or Other (legacy) |
| Ratio |
| 1.26 |
| 2-Sided |
| 90 |
| 1.08 |
| 1.47 |
Ratio of Geometric LS mean is for R-warfarin. |
| Superiority or Other (legacy) |
| Total Analytes |
|
| Total Analytes |
|
| Total Analytes |
|
| Total Analytes |
|
| Ratio of Geometric LS Means |
| 1.02 |
| 2-Sided |
| 90 |
| 0.98 |
| 1.06 |
Ratio of Geometric LS mean for Period 2, Day 14, 4 hours. |
| Superiority or Other (legacy) |