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

NCT01263093 | Completed Phase 1 Results

• 2 other identifiers: 12593H9P-EW-LNBY
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (4)

• Pharmacokinetics of R-130964, Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞)

  R-130964 is the active metabolite of clopidogrel. Blood samples were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684.

  predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose

• Pharmacokinetics of R-130964, Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-tlast)

  R-130964 is the active metabolite of clopidogrel. Blood samples were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684. Log-transformed AUC0-tlast was analyzed using a linear mixed effects model with sequence, period, and treatment as fixed effects and participant as a random effect.

  predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose

• Pharmacokinetics of R-130964, Maximum Observed Drug Concentrations (Cmax)

  R-130964 is the active metabolite of clopidogrel. Blood samples were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684. Log-transformed Cmax was analyzed using a linear mixed effects model with sequence, period, and treatment as fixed effects and participant as a random effect.

  predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose

• Pharmacokinetics of R-130964, Time to Maximum Observed Drug Concentrations (Tmax)

  R-130964 is the active metabolite of clopidogrel. Blood samples were collected prior to and through 24 hours after administration of clopidogrel alone and in combination with LY2216684.

  predose and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours postdose

Secondary Outcomes (1)

• Percentage Inhibition of Platelet Aggregation

  predose and 2, 4, and 24 hours postdose

Study Arms (2)

Clopidogrel First, Then LY2216684 + Clopidogrel

EXPERIMENTAL

Period 1: a single 300-milligram (mg) dose of clopidogrel administered orally on Day 1 (Treatment 1). Period 2: an 18-mg dose of LY2216684 administered orally, once daily (QD) on Days 1 through 3, plus a single 300-mg dose of clopidogrel administered orally on Day 3 (Treatment 2). There was a washout period of at least 14 days between the last dose of study drug in Period 1 and the first dose in Period 2.

Drug: Clopidogrel; Drug: LY2216684

LY2216684 + Clopidogrel First, Then Clopidogrel

EXPERIMENTAL

Period 1: an 18-milligram (mg) dose of LY2216684 administered orally, once daily (QD) on Days 1 through 3, plus a single 300-mg dose of clopidogrel administered orally on Day 3 (Treatment 2). Period 2: a single 300-mg dose of clopidogrel administered orally on Day 1 (Treatment 1). There was a washout period of at least 14 days between the last dose of study drug in Period 1 and the first dose in Period 2.

Drug: Clopidogrel; Drug: LY2216684

Interventions

Clopidogrel DRUG

Clopidogrel First, Then LY2216684 + Clopidogrel; LY2216684 + Clopidogrel First, Then Clopidogrel

LY2216684 DRUG

Clopidogrel First, Then LY2216684 + Clopidogrel; LY2216684 + Clopidogrel First, Then Clopidogrel

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 - 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 milli-international units per milliliter \[mIU/mL\]).
• Have a body weight \>50 kilograms (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 (CYP) 2C19 extensive metabolizers or ultra -rapid 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, 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 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 of 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 milliliters (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 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

Clopidogrel; 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)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; 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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• 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: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: October 22, 2018
• Results First Posted: October 22, 2018

Record last verified: 2018-03

Locations

US (1)