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.
Study Type
INTERVENTIONAL
Purpose
OTHER
Masking
NONE
Enrollment
13
Administered orally
Administered orally
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, 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, 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, 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, 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, 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, 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, France
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.
Time frame: 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
Time frame: 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.
Time frame: Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 hours postdose
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.
Time frame: Period 2 Days 14 and 15 (19 up to 30 days): Predose, up to 24 hours postdose
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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)
Time frame: 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.)
Time frame: 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.
Time frame: Period 2 Day 14 (19 up to 30 days): Predose and 4 hours postdose
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