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 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