A Pharmacokinetic Study on the Effect of LY2216684 on the Active Metabolite of Clopidogrel

Study Description

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Brief Summary:

The purpose of this study is to measure how much of the study drugs reach the blood stream and how long it takes the body to get rid of them, and determine how clopidogrel and LY2216684 might affect each other in the body. Information about any side effects that may occur will also be collected.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder	Drug: Clopidogrel; Drug: LY2216684 + clopidogrel	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	47 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Effect of LY2216684 on the Pharmacokinetics and Pharmacodynamics of R-130964, the Active Metabolite of Clopidogrel, in Healthy Subjects
Study Start Date :	December 2010
Actual Primary Completion Date :	March 2011
Actual Study Completion Date :	March 2011

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Clopidogrel, LY2216684 + Clopidogrel; Clopidogrel as a single oral 300 mg dose on day 1 in first intervention period, and LY2216684 as an 18 mg oral dose on days 1-3 plus clopidogrel as a single oral 300 mg dose on day 3 in second intervention period (after a 14 day washout period).	Drug: Clopidogrel; Administered orally Drug: LY2216684 + clopidogrel; Administered orally
Experimental: LY2216684 + Clopidogrel, Clopidogrel; LY2216684 as an 18 mg oral dose on days 1-3 plus clopidogrel as a single oral 300 mg dose on day 3 in first intervention period, and clopidogrel as a single oral 300 mg dose on day 1 in second intervention period (after a 14 day washout period).	Drug: Clopidogrel; Administered orally Drug: LY2216684 + clopidogrel; Administered orally

Outcome Measures

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Primary Outcome Measures :

1. Pharmacokinetics of R-130964, area under the concentration-time curve from time 0 to infinity (AUC,0-∞) [ Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hours on days 1 and 3 ]
2. Pharmacokinetics of R-130964, maximum observed drug concentrations (Cmax) [ Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hours on days 1 and 3 ]
3. Pharmacokinetics of R-130964, time to maximum observed drug concentrations (tmax) [ Time Frame: predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hours on days 1 and 3 ]

Secondary Outcome Measures :

1. Inhibition of platelet aggregation [ Time Frame: pre-dose, 2, 4, and 24 hours on days 1 and 3 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 65 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• Are overtly healthy, as determined by medical history and physical examination.
• Male subjects - Agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug.
• Female subjects - Are women of child-bearing potential who test negative for pregnancy at the time of enrollment, have used a reliable method of birth control for 6 weeks prior to administration of study drug, and agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug; or Women not of child-bearing potential due to surgical sterilization(hysterectomy or bilateral oophorectomy or tubal ligation) or menopause (at least 1 year without menses or 6 months without menses and a follicle stimulating hormone [FSH] >40 mIU/mL).
• Have a body weight >50 kg.
• Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator.
• Have venous access sufficient to allow blood sampling as per the protocol.
• Have normal blood pressure and pulse rate (sitting position) as determined by the investigator.
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.
• Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site.
• Are CYP2C19 extensive metabolizers as determined by genotyping assessment.

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device other than the study drug, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Have known allergies to LY2216684, clopidogrel, or related compounds.
• Are persons who have previously completed or withdrawn from this study or any other study investigating LY2216684 within 6 months prior to screening.
• Have an abnormality in the 12-lead ECG that, in the opinion of the investigator, increases the risks associated with participating in the study.
• Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data.
• Have a history or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation.
• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening.
• Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies.
• Show evidence of hepatitis C and/or positive hepatitis C antibody.
• Show evidence of hepatitis B and/or positive hepatitis B surface antigen.
• Are women with a positive pregnancy test or women who are lactating.
• Intend to use over-the-counter or prescription medication within 14 days prior to dosing unless deemed acceptable by the investigator and Sponsor's medical monitor, except for influenza vaccinations
• Use of any drugs or substances that are known to be substrates, inducers, or inhibitors of CYP2C19 or CYP3A4 within 30 days prior to dosing.
• Have donated blood of more than 500 mL within the last month.
• Have an average weekly alcohol intake that exceeds 14 units per week, or are unwilling to stop alcohol consumption 48 hours prior to check-in until completion of the study (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits).
• Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any subjects unwilling to adhere to study caffeine restrictions.
• Have used any tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to enrollment.
• Have consumed grapefruit or grapefruit-containing products 7 days prior to enrollment and during the study.
• Have a documented or suspected history of glaucoma.
• History or presence of significant bleeding disorders that is, haematemesis, melanena, severe or recurrent epistaxis, haemoptysis, clinically overt clinical haematuria or intracranial haemorrhage.
• Subjects with a history of gastrointestinal ulcers or haemorrhage.
• Personal or family history of coagulation or bleeding disorders or reasonable suspicion of vascular malformations, for example, cerebral haemorrhage, aneurysm or premature stroke (cerebrovascular accident <65 years of age).
• Self-reported history of increased bleeding from trauma (for example, prolonged bleeding after tooth extraction).
• History of major surgery within 3 months of screening.
• Planned surgery within 14 days after the last day of dosing.
• International normalized ratio (INR), prothrombin time (PT), activated partial thromboplastin time (APTT) above the normal reference range or platelet count below the normal reference range at screening.
• Positive fecal occult blood examination at screening.
• Clinically significant abnormality in fundoscopic or petechiae examination.
• Consumption of aspirin, other non-steroidal anti-inflammatory drugs or other drugs known to affect platelet function within 21 days prior to dosing.
• Subjects determined to be unsuitable by the investigator for any reason.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Texas
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.
Dallas, Texas, United States

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Director:	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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier:	NCT01263093 History of Changes
Other Study ID Numbers:	12593; H9P-EW-LNBY ( Other Identifier: Eli Lilly and Company )
First Posted:	December 20, 2010
Last Update Posted:	May 5, 2011
Last Verified:	May 2011

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; Clopidogrel; Ticlopidine; Phenylethyl Alcohol; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists	Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Fibrinolytic Agents; Fibrin Modulating Agents; Cytochrome P-450 CYP2C19 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Anti-Infective Agents, Local; Anti-Infective Agents; Disinfectants