A Study to Evaluate the Effect of Genotype on LY2216684

NCT01460381 | Completed Phase 1 Results

• 2 other identifiers: 14397H9P-EW-LNDZ
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate how genetic profiles respond to LY2216684 and the effect of Quinidine on the pharmacokinetics (PK) of LY2216684 in a specific genetic profile. Side effects will be documented.

Conditions

Depressive Disorder, Major

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [AUC(0-∞)] of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM)

  Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.

  Predose up to 120 hours post administration of LY2216684

• Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM)

  Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.

  Predose up to 120 hours post administration of LY2216684

• Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of LY2216684 in Cytochrome P450 (CYP)2C19 Extensive Metabolizers (EM) Versus Poor Metabolizers (PM)

  Blood samples were collected prior to and up to 120 hours following dosing of LY2216684 on Day 1 (Period 1) for the measurement of LY2216684 plasma concentrations.

  Predose up to 120 hours post administration of LY2216684

Secondary Outcomes (3)

• Pharmacokinetics: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity [(AUC(0-∞)] of LY2216684 + Quinidine in Cytochrome P450 (CYP)2C19 Poor Metabolizers (PM)

  Predose up to 120 hours post administration of quinidine

• Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of LY2216684 + Quinidine in CYP2C19 Poor Metabolizers

  Predose up to 120 hours post administration of quinidine

• Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of LY2216684 + Quinidine in CYP2C19 Poor Metabolizers

  Predose up to 120 hours post administration of quinidine

Study Arms (2)

LY2216684 + Quinidine (CYP2C19 poor metabolizers)

EXPERIMENTAL

Participants were predicted to have a cytochrome P450 (CYP)2C19 poor metabolizer (PM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 was administered on Day 1. Period 2 (Days 8-15): 300 mg quinidine sulfate controlled release was administered orally, once daily on Days 8-15. Additionally, a single, oral dose of 18 mg LY2216684 was administered on Day 11.

Drug: LY2216684; Drug: Quinidine

LY2216684 (CYP2C19 extensive metabolizers)

EXPERIMENTAL

Participants were predicted to have a cytochrome P450 (CYP)2C19 extensive metabolizer (EM) phenotype, as determined by genotyping analysis. Period 1 (Days 1-7): a single, oral dose of 18 milligrams (mg) LY2216684 administered on Day 1. Period 2 (Days 8-15): EM participants did not participate in this period.

Drug: LY2216684

Interventions

LY2216684 DRUG

LY2216684 (CYP2C19 extensive metabolizers); LY2216684 + Quinidine (CYP2C19 poor metabolizers)

Quinidine DRUG

Also known as: Quinidine sulfate controlled release (CR)

LY2216684 + Quinidine (CYP2C19 poor metabolizers)

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 males or females, 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 (not including hormonal contraceptives) for 4 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 the study drug or; Are women not of child-bearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation/occlusion) or menopause (at least 1 year without menses or 6 months without menses and a follicle stimulating hormone \[FSH\] level \>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 for blood sampling as per the protocol
• 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 institutional review board (IRB) governing the site
• Have normal blood pressure (BP) and pulse rate (PR) (sitting position) as determined by the investigator
• Are predicted to have cytochrome P450 (CYP)2C19 extensive metabolizer (EM) or poor metabolizer (PM) phenotypes as determined by genotyping assessment
• Are predicted to have CYP2D6 EM phenotype as determined by genotyping assessment.

You may not qualify if:

• Are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product; 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/intolerance to LY2216684 or quinidine, related compounds, or any components of the formulation
• Are persons who have previously received the investigational product in this study or have 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 or show evidence of significant active neuropsychiatric disease or have a history of suicide attempt or ideation
• 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
• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening
• Show evidence of human immunodeficiency virus (HIV) infection 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 or during the study unless deemed acceptable by the investigator and Sponsor's medical monitor. Exceptions include influenza vaccinations, the use of topical medication (provided there is no evidence of chronic dosing with the risk of systemic exposure), occasional use of acetaminophen/paracetamol/ibuprofen, and hormone replacement therapy including thyroid replacement (stable dose for at least 1 month).
• Have donated blood of more than 500 milliliters (mL) within the last month
• Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or are unwilling to stop alcohol consumption 48 hours prior to dosing in Period 1 until Discharge (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)
• Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any participants unwilling to stop caffeine consumption from 48 hours prior to dosing in Period 1 until Discharge

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

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

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cinchona Alkaloids; Alkaloids; Heterocyclic Compounds; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Quinolines; 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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2011
• First Posted: October 26, 2011
• Study Start: October 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: October 26, 2018
• Results First Posted: October 26, 2018

Record last verified: 2018-03

Locations

US (1)