Solid TumorPhase 1NCT01388335
A Drug Interaction Study to Assess the Effect of LY317615 on the Metabolic Pathway of Warfarin
A Phase 1 study testing warfarin and enzastaurin in people with Solid Tumor and Lymphoma, Malignant, run by Eli Lilly and Company at 7 sites in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Solid Tumor, Lymphoma, Malignant
- What is being tested?
- warfarin and enzastaurin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 7 sitesFrance
- Study dates
- Aug 2011to Dec 2012
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
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- 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)
Who cannot join
- 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.
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- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
France7 sites
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
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
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
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
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
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
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
About this study
Official title: The Effect of Enzastaurin on CYP2C9: Enzastaurin - S-Warfarin Drug Interaction Study in Patients With Cancer
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.
- Conditions
- Solid Tumor, Lymphoma, Malignant
- Being tested
- warfarin, enzastaurin
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
warfarinDrug
Administered orally
enzastaurinDrug
Also called LY317615
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: warfarin; Drug: enzastaurin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: 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.
Measured: Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 hours postdose
Secondary outcomes (9)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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.)
Measured: 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.
Measured: Period 2 Day 14 (19 up to 30 days): Predose and 4 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2011 (estimated)
- Study startAug 2011
- Primary completionOct 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01388335
- Sponsor's protocol ID
- 9763
- Other IDs
- H6Q-MC-JCAX
- Status last verified
- Jun 2020
- First submitted
- 4 Jul 2011
- Last updated
- 1 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Enzastaurin on CYP2C9: Enzastaurin - S-Warfarin Drug Interaction Study in Patients With Cancer
- ClinicalTrials.gov ID
- NCT01388335
- Acronym / sponsor ID
- 9763
- Conditions
- Solid Tumor, Lymphoma, Malignant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2011
- Primary completion
- Oct 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 6 Jul 2011 (estimated)
- Results
- Posted 1 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| warfarin + enzastaurin | Experimental | Drug: warfarin, Drug: enzastaurinOn 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| warfarinAdministered orally | Drug | warfarin + enzastaurin |
| enzastaurinAlso: LY317615Administered orally | Drug | warfarin + enzastaurin |
Primary outcome
Pharmacokinetics: Maximum Plasma Concentration (Cmax) 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
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.
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
Time frame: Period 1 Day 1 (8 days) and Period 2 (19 up to 30 days): Predose, up to 96 hours postdose
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.
9 secondary outcomes
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) at Steady State of Enzastaurin, Its Principle Metabolites and Total Analyte
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
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
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
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
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
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
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
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
Time frame: Period 2 Day 14 (19 up to 30 days): Predose and 4 hours postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing warfarin and enzastaurin in people with Solid Tumor and Lymphoma, Malignant, run by Eli Lilly and Company at 7 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics: Maximum Plasma Concentration (Cmax) 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2020.