A Study of LY2216684 and Warfarin in Healthy Subjects

This study has been completed.
Sponsor:
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01263119
First received: December 16, 2010
Last updated: April 18, 2011
Last verified: April 2011
  Purpose

The purpose of this study is to determine how warfarin might affect LY2216684 and how giving LY2216684 might affect warfarin in the body. Information about any side effects that may occur will also be collected.


Condition Intervention Phase
Major Depressive Disorder
Drug: Warfarin
Drug: LY2216684
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of LY2216684 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Pharmacokinetics (PK) of S-warfarin, area under the concentration curve (AUC,0-∞) [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post warfarin administration ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) of S-warfarin, maximum concentration (Cmax) [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post warfarin administration ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) of S-warfarin, time to concentration maximum (tmax) [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post warfarin administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics (PK) of R-warfarin, area under the concentration curve (AUC,0-∞) [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post warfarin administration ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) of R-warfarin, concentration maximum (Cmax) [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post warfarin administration ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics (PK) of R-warfarin, time to concentration maximum (tmax) [ Time Frame: Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post warfarin administration ] [ Designated as safety issue: Yes ]
  • Area under the INR (international normalized ratio) curve [ Time Frame: Predose, 6, 12, 24, 48, 72, 96, 120, 144 hours after warfarin administration ] [ Designated as safety issue: Yes ]
  • Maximum observed INR response [ Time Frame: Predose, 6, 12, 24, 48, 72, 96, 120, 144 hours after warfarin administration ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: December 2010
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Warfarin, LY2216684+Warfarin
Single oral dose of 10 mg warfarin on Day 1 in period 1. Oral dose of 18 mg LY2216684 once daily (QD) on Days 1 to 12, with a single oral dose of 10 mg warfarin co-administered on Day 3 in period 2. There is a washout period of at least 14 days between dosing periods.
Drug: Warfarin
administered orally
Drug: LY2216684
administered orally

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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 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 CYP2C9 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, warfarin, 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 electrocardiogram (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 (including hormonal contraceptives) within 14 days prior to dosing unless deemed acceptable by the investigator and Sponsor's medical monitor
  • Use of any drugs or substances that are known to be substrates, inducers, or inhibitors of CYP2C19 or CYP2C9 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 dosing in each period and while resident at the CRU (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, hematemesis, melanena, severe or recurrent epistaxis, hemoptysis, clinically overt hematuria or intracranial hemorrhage.
  • Subjects with a history of gastrointestinal ulcers or hemorrhage.
  • Personal or family history of coagulation or bleeding disorders or reasonable suspicion of vascular malformations, for example, cerebral hemorrhage, 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.
  • INR/PT, or activated partial thromboplastin time (APTT) above the normal reference range at screening.
  • Positive fecal occult blood examination at screening.
  • Female subjects with a history of menorrhagia.
  • Subjects determined to be unsuitable by the investigator for any reason.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01263119

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

No publications provided

Responsible Party: Chief Medical Officer, Eli Lilly
ClinicalTrials.gov Identifier: NCT01263119     History of Changes
Other Study ID Numbers: 12595, H9P-EW-LNCF
Study First Received: December 16, 2010
Last Updated: April 18, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Depressive Disorder, Major
Depressive Disorder
Depression
Mood Disorders
Mental Disorders
Behavioral Symptoms
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014