A Drug Interaction Study to Assess the Effect of LY317615 on the Metabolic Pathway of Warfarin

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:

  * Participants receiving luteinizing hormone-releasing hormone (LHRH) analogue therapy (leuprolide, goserelin, or triptorelin) prior to starting this study should have that therapy continued while on this study.
  * In addition, participants who have received nonsteroidal antiandrogen therapy in the form of bicalutamide should have discontinued therapy at least 6 weeks prior to study entry (4 weeks if on flutamide or nilutamide).
* Have adequate organ function including:

  * Bone Marrow Reserve: absolute neutrophil count (ANC) ≥1.5 x 10˄9/liter (L) prior to treatment, platelets ≥100 x 10˄9/L, and hemoglobin ≥10 grams/deciliter (g/dL). Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Participants may be allowed erythropoietin of choice as per standard of care.
  * Hepatic: bilirubin within 1.5 times the upper limit of normal (ULN), and transaminases ≤2.5 times ULN or ≤5 times ULN when liver metastases are known.
  * Renal: serum creatinine ≤1.5 milligrams/deciliter (mg/dL).
* 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:

* Have received treatment within 28 days of the initial dose of study drug with an experimental agent for non-cancer indications that has not received regulatory approval for any indication
* Participants with glioblastoma, Central Nervous System (CNS) metastases, or hematologic malignancies other than lymphoma are excluded from this study.
* Serious concomitant systemic disorder, including active infection, incompatible with the study (at the discretion of the investigator)
* History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infections
* Cardiac: Have a serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease, as defined by the New York Heart Association Class III or IV. Participants with a QTcB prolongation \>450/470 millisecond (msec) (males/females) and participants who have a congenital long-QT-syndrome in their own or family medical history should be excluded at the investigator's discretion. Participants with intraventricular conduction delays (for instance, right or left bundle branch blocks) should also be excluded.
* It is recommended that participants with baseline arrhythmias (persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation \[occasional premature atrial contractions \[APCs\] or premature ventricular contractions \[PVCs\] are acceptable\] or bradycardia (heart rate \<50) be excluded, at the investigator's discretion.
* Known family history of unexplained sudden death
* Personal history of unexplained syncope within the last year
* The use of concomitant medications that prolong the QT/QTc interval
* Participants with complete gastrectomy or other significant GI diseases that, in the investigator's opinion, may significantly impact drug absorption
* Participants on total parenteral nutrition (TPN)
* Inability to swallow tablets
* Women who are lactating
* Participants with known allergies to enzastaurin or warfarin
* Participants with warfarin-related skin necrosis
* Participants who are known cytochrome P450 (CYP) 2C9 poor or intermediate metabolizers
* Drugs that are known inhibitors or inducers of CYP3A are specifically excluded. Foods that are known inhibitors of CYP3A (for example, grapefruit or grapefruit juice or Seville oranges or Seville orange juice) are also specifically excluded during Period 1 and Period 2 of the study.
* Drugs with narrow therapeutic windows and that are also known substrates of CYP2C9, CYP2C8, CYP2C19, and CYP3A are excluded.
* Use of any known inducers or inhibitors of CYP2C9 within 30 days (or at least 5 half-lives, whichever is shorter) prior to enrollment. Drugs that are inhibitors or inducers of CYP2C9 are also excluded throughout Periods 1 and 2. Drugs that are known to increase the hypoprothrombinemic effect of warfarin are excluded prior to enrollment and throughout Periods 1 and 2.
* Use of other anticoagulants or antithrombolytics within 14 days prior to screening or during Periods 1 and 2
* Use of low-dose aspirin (or higher doses) within 14 days prior to screening and during Period 1 and 2 of the study (allowed during continued safety extension phase)
* Use of high-dose acetaminophen (paracetamol) within 14 days of Period 1 and during Period 1 and 2 of the study
* Participants who have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) or participants unwilling to stop alcohol consumption for the duration of the drug interaction phase (Periods 1 and 2) of the study (1 unit = 12 ounces (oz) or 360 milliliters (mL) of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
* Use of drugs of abuse, as evidenced by history, and/or positive findings on urinary drug screening, unless prescribed by a physician (for example, narcotic pain medication)
* Failure for any reason to satisfy the investigator for adequate fitness to participate in the study
* Major surgery or lumbar puncture in the past 6 weeks
* Protein C (functional) activity or Protein S antigen concentration below the normal range
* Heme-positive stool
* Warfarin is contraindicated in the case of congenital galactosemia, malabsorption syndromes of glucose and galactose, or lactase deficiency