A Study of LY2216684 and Warfarin in Healthy Subjects

NCT01263119 | Completed Phase 1 Results

• 2 other identifiers: 12595H9P-EW-LNCF
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of S-Warfarin

  Least Squares (LS) geometric mean was based on AUC0-∞ of S-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2.

  Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) of S-Warfarin

  Least Squares (LS) geometric mean was based on Cmax of S-warfarin; calculated when warfarin was administered alone (reference) on Day 1 of Period 1 and coadministered with LY2216684 (test) on Day 3 of Period 2.

  Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3

• Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of S-Warfarin

  This outcome was measured based on Tmax of S-warfarin on Day 1 of Period 1 when warfarin was administered alone (reference) and on Day 3 of Period 2 when coadministered with LY2216684 (test).

  Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3

Secondary Outcomes (5)

• Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of R-Warfarin

  Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3

• Pharmacokinetics: Maximum Plasma Concentration (Cmax) of R-Warfarin

  Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3

• Pharmacokinetics: Time to Maximum Concentration (Tmax) of R-Warfarin

  Pre-dose, 1, 2, 3, 4, 5, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post-warfarin administration on Days 1 and 3

• Pharmacodynamics: Area Under the Curve of the International Normalized Ratio (AUCINR) of Warfarin

  Predose, 6, 12, 24, 48, 72, 96, 120, 144 hours post-warfarin administration on Days 1 and 3

• Pharmacodynamics: Maximum Observed International Normalized Ratio (INRmax)

  Predose, 6, 12, 24, 48, 72, 96, 120, 144 hours post-warfarin administration on Days 1 and 3

Study Arms (1)

Warfarin, LY2216684 + Warfarin

EXPERIMENTAL

Period 1: Single 10-milligram (mg) warfarin oral dose on Day 1; Washout Period of at least 14 days; Period 2: 18-mg LY2216684 oral dose, once daily on Days 1 to 12, with single 10-mg warfarin oral dose coadministered on Day 3.

Drug: Warfarin; Drug: LY2216684

Interventions

Warfarin DRUG

10-mg warfarin oral dose

Warfarin, LY2216684 + Warfarin

LY2216684 DRUG

18-mg LY2216684 oral dose

Warfarin, LY2216684 + Warfarin

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are overtly healthy, as determined by medical history and physical examination
• Male participants - Agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug
• Female participants - 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 mass International Units per milliliter \[mIU/mL\])
• Have body weight \>50 kilogram (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 cytochrome P450 2C9 (CYP2C9) extensive metabolizers, as determined by genotyping assessment

You may not qualify if:

• 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 cytochrome P450 2C19 (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 ounces \[oz\] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

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

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Warfarin; alpha-((5-fluoro-2-methoxyphenyl)methyl)-alpha-(tetrahydro-2H-pyran-4-yl)-2-morpholinemethanol

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2010
• First Posted: December 20, 2010
• Study Start: December 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: January 22, 2019
• Results First Posted: October 19, 2018

Record last verified: 2019-01

Locations

US (1)